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DAVIDE ZAFFE

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Dipartimento di Studi Linguistici e Culturali

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Pubblicazioni

2024 - Long-term stability (21-30 years) of root coverage outcomes using sub-epithelial connective tissue grafts at single or multiple gingival recessions: A longitudinal case series [Articolo su rivista]
Bertoldi, Carlo; Consolo, Ugo; Lalla, Michele; Zaffe, Davide; Tanza, Donato; Cairo, Francesco; Cortellini, Pierpaolo
abstract

Aim: To evaluate outcomes and predictive factors for the long-term stability of root coverage using a sub-epithelial connective tissue graft. Materials and methods: One-hundred and two healthy subjects (221 gingival recessions, GRs) were treated from 1987 to 1996. Keratinized tissue width (KTW), GR depth (RD), GR width (RW) and GR area (RA) were evaluated at baseline (M0) and at 1 month (M1), 1 year (M2), 11 years (M3), 21 years (M4) and 27 years (M5) after surgery. Primary outcomes consisted of complete root coverage (cRC) and relative dimensional changes in recession depth (measured in mm [c%-RD]), recession width (measured in mm [c%-RW]) and recession area (measured in mm2 [c%-RA]). Results: cRC was 88.7% at 1 year (M2), 59.8% at M3, 44.4% at M4 and 51.9% at M5. Average c%-RD was 95.2% at 1 year, 81.9% at M3, 71.5% at M4 and 81.7% at M5. KTW increased after surgery and over time and was positively correlated with favourable outcomes. Increased baseline RA was associated with less favourable clinical outcomes. Conclusions: The sub-epithelial connective tissue graft is effective in the treatment of GRs and facilitates long-term stability of clinical outcomes. Wider baseline RA was a strong predictor of unfavourable short- and long-term RC outcomes.

2022 - Cortical Versus Cancellous Solvent-Dehydrated Bone Allograft for Alveolar Ridge Preservation: A Histologic Study [Articolo su rivista]
Soardi, C. M.; Barootchi, S.; Soardi, B.; Tavelli, L.; Zaffe, D.; Wang, H. -L.
abstract

Allografts have been routinely used for immediate grafting of extraction sites as modalities of alveolar ridge preservation (ARP). Solvent-dehydrated bone allograft (SDBA), which is commonly utilized for socket grafting, exists in the form of cortical and cancellous particles. This study aims to provide a histologic comparison of cortical and cancellous SDBA for ARP. A total of 35 extraction sockets were allocated to receive either a cortical (17 sites) or cancellous (18 sites) SDBA, followed by application of a resorbable collagen wound dressing in both groups. At approximately 4 months, a bone core biopsy sample was obtained during implant placement. Histomorphometric assessment was then conducted to compare the differences between both forms of SDBA. Within its limitations, a higher percentage of vital bone was observed in the cortical bone group compared to the cancellous bone group (28.6% vs 20.1%, respectively, P = .042), while there was a lack of statistically significant differences among other fractions of the bone biopsy sample (residual graft particles and nonmineralized tissues such as connective tissue or other components).

2022 - Influence of apico-coronal positioning of tissue-level implants on marginal bone stability during supracrestal tissue height establishment: A multi-center prospective study [Articolo su rivista]
Spinato, Sergio; Bernardello, Fabio; Lombardi, Teresa; Soardi, Carlo Maria; Messina, Marcello; Zaffe, Davide; Stacchi, Claudio
abstract

Introduction Supracrestal tissue height establishment is a crucial factor influencing peri-implant marginal bone modifications prior to prosthesis delivery. If mucosal thickness is insufficient, peri-implant marginal bone resorption occurs to allow appropriate supracrestal tissue height formation. This study evaluates if marginal bone resorption occurring around tissue-level implants before prosthetic loading could be compensated by adapting apico-coronal positioning to mucosal thickness. Methods Patients requiring placement of one single implant in the posterior mandible were treated with tissue-level implants with a 3-mm high transmucosal machined component and moderately rough implant body. Based upon vertical mucosal thickness measured after buccal flap reflection, implants were placed with the treated part: (group 1) 2 mm below crestal level in presence of thin mucosa (<2.5 mm); (group 2) 1 mm below the crestal level in presence of medium mucosa (2.5-3.5 mm); (group 3) at equicrestal level in presence of thick mucosa (>3.5 mm). Results Forty-nine implants, placed in 49 patients were included in final analysis (group 1: 18 implants; group 2: 16 implants; group 3: 15 implants). Mean marginal bone resorption after 5 months of healing was 0.66 +/- 0.49 mm, 0.32 +/- 0.41 mm, and 0.22 +/- 0.52 mm in groups 1, 2, and 3, respectively. Inter-group analysis highlighted significant differences between the three groups after ANOVA test (p = 0.025). However, adaptation of apico-coronal implant positioning in relation to mucosal thickness, allowed to avoid early exposure of the treated surface in 100%, 93.7%, and 53.3% of the implants in groups 1, 2, and 3, respectively. Conclusion During supracrestal tissue height formation, tissue-level implants inserted adapting apico-coronal positioning in relation to mucosal thickness exhibited greater marginal bone resorption at sites with thin mucosa than at sites with medium or thick mucosa. However, anticipating supracrestal tissue height establishment by adapting apico-coronal implant positioning in relation to mucosal thickness may effectively prevent unwanted exposure of treated implant surface.

2021 - Influence of tooth-brushing on early healing after access flap surgery: A randomized controlled preliminary study [Articolo su rivista]
Bertoldi, C.; Generali, L.; Cortellini, P.; Lalla, M.; Luppi, S.; Tomasi, A.; Zaffe, D.; Salvatori, R.; Bergamini, S.
abstract

In the present study, the clinical outcomes obtained using three different protocols of post-operative plaque control for the 4 weeks after surgery were compared. Thirty healthy subjects, presenting at least one periodontal pocket requiring resective surgery, were selected and randomly distributed to three different groups corresponding to respective post-surgical protocols: (A) toothbrushes + chlorhexidine + anti-discoloration system (ADS + CHX); (B) toothbrushes + chlorhexidine (CHX); (C) only toothbrushes. The full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), probing pocket depth (PPD), recession depth (REC), clinical attachment level (CAL), and bleeding on probing (BoP) were measured in six aspects per tooth (mesio-buccal (MB), buccal (B), disto-buccal (DB), disto-lingual (DL), lingual (L), and mesio-lingual (ML)) at baseline, 3 months, and 6 months after surgery. FMPS and FMBS did not significantly change (p > 0.05), whereas PPD and CAL significantly decreased, and REC significantly increased in all groups during the study (p < 0.05). Clinical results were satisfactory in all cases, with no significant differences between groups 3 months after surgery. Six months after surgery, only PPD-MB was significantly different in the three groups (p < 0.05). Nevertheless, this value was not clinically relevant because the value of PPD-B (about 2 mm) in group C was physiologic. The mechanical plaque control was proven to be fundamental and sufficient in all the six aspects per tooth to guarantee an excellent clinical outcome without the need of chemical plaque control.

2021 - Topographic Assessment of Calcified Material After Sinus Floor Augmentation [Articolo su rivista]
Soardi, Carlo M; Zaffe, Davide; Soardi, Barbara; Wang, Hom-Lay
abstract

Purpose: This study aimed to topographically examine the healing of mineralized human bone allograft in sinus augmentation. Materials and Methods: Thirty-two patients with crestal bone height <= 2 mm who required sinus augmentation were recruited for the study. A mixture of 80/20 cortical/cancellous mineralized human bone allografts were used to augment the sinus floor using a crestal window approach. A bone core biopsy specimen was taken at the time of implant placement, 6 months after surgery. Microradiographs of methacrylate-embedded sections were split into five longitudinal sectors (crestal to sinusal) to topographically assess the bone, graft, and fibrous tissue amount. Results: All implants were osseointegrated 3 months later without any adverse effects. The polynomial (degree 2) of results (all with great correlation coefficient, P < .01) gave rise to a polynomial curve of graft percentage with a maximum at sector 4 (presinusal), a bone percentage with a minimum between sectors 3 and 4, and a fibrous tissue percentage with a maximum between sectors 3 and 4. Conclusion: Based upon topographic analysis, mineralized human bone allograft is capable of achieving adequate vertical bone height for implant placement. The need for a topographic analysis to assess the outcomes of sinus augmentation is emphasized. Int J Oral Maxillofac Implants 2021;36:1219-1223. doi: 10.11607/jomi.7569

2020 - Clinical analysis on efficacy of root-surface conditioning by ethylenediaminetetraacetic acid on surgical treatment of gingival recessions with coronally advanced flap and enamel matrix derivative peptide: A retrospective study [Articolo su rivista]
Bertoldi, C.; Cortellini, P.; Spinato, S.; Zaffe, D.
abstract

2020 - Clinical and histological reaction of periodontal tissues to subgingival resin composite restorations [Articolo su rivista]
Bertoldi, C; Monari, E; Cortellini, P; Generali, L; Lucchi, A; Spinato, S; Zaffe, D
abstract

Objectives: To compare the clinical and histological response of supracrestal periodontal tissues to subgingival composite restorations versus natural root surfaces Material and methods: In 29 subjects with a single tooth requiring subgingival restorations, a deep margin elevation (DME) procedure with composite resin was applied. Full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), and focal probing depth (PD) were measured at baseline, before DME, and after 3 months. The distance between the coronal marked (CM) point to the apical margin of the composite reconstruction (AMR), at baseline, and to the tip of the periodontal probe inserted to reach the bottom of the sulcus (APP), 3 months later, was measured. An all-around secondary flap, harvested to ensure the subsequent single-crown prosthetic rehabilitation was histologically processed. The histological inflammation degree was evaluated in areas of gingival tissues adjacent to the composite (group B) and adjacent to the natural surface of each single tooth (group A). Results: Significant FMPS, FMBS, and PD decreases were observed (p < 0.05). CM-AMR and CM-APP were significantly different (p < 0.05), suggesting an attachment gain after 3-months. The inflammation level of gingival tissue was similar in groups A and B (p > 0.05). Conclusions: For the first time, this topic was clinically and histologically studied in humans. Subgingival restorations resulted compatible with gingival health, with levels similar to that of untreated root surfaces. Clinical relevance: Deep margin elevation procedure produces favorable clinical and histological outcomes allowing a routine utilization in reconstructive dentistry.

2020 - Extraction socket healing in leukemic patients: a preliminary radiographic evaluation [Articolo su rivista]
Bertoldi, C; Generali, L; Forabosco, A; Zaffe, D; Ferrari, M; Narni, F
abstract

2020 - Influence of abutment height and vertical mucosal thickness on early marginal bone loss around implants: A randomised clinical trial with an 18-month post-loading clinical and radiographic evaluation [Articolo su rivista]
Spinato, Sergio; Stacchi, Claudio; Lombardi, Teresa; Bernardello, Fabio; Messina, Marcello; Dovigo, Sergio; Zaffe, Davide
abstract

Abstract Purpose: To investigate the influence of vertical mucosal thickness on marginal bone loss around implants with short and long prosthetic abutments and the marginal bone loss progression rate up to 18 months after prosthetic loading. Materials and methods: Internal hex platform-switched implants were placed equicrestally using a two-stage protocol in the posterior mandible of two groups of patients with different vertical mucosal thickness, thin (≤ 2.0 mm) and thick (> 2.0 mm). Elevated prosthetic abutments of different heights (1 mm or 3 mm) were randomly assigned for single screw-retained crowns in both groups. Mesial and distal marginal bone loss were measured at implant placement (T0) and crown delivery (after 4 months [T1]), and after 6 (T2), 12 (T3) and 18 months (T4) of functional loading. Results: Eighty implants were placed in eighty patients. Three patients dropped out at T2. At T4, 74 out of 77 implants were functioning, resulting in a 96% survival rate. Marginal bone loss (mean ± SE) at T2 was significantly greater in the 1-mm abutment groups (0.61 ± 0.09 mm with thin mucosa; 0.64 ± 0.07 mm with thick mucosa) than in the 3-mm abutment groups (0.32 ± 0.07 mm with thin mucosa; 0.26 ± 0.04 mm with thick mucosa). The marginal bone loss pattern over 18 months of loading showed that the greatest amount of marginal bone loss occurred during the first 6 months of function. Conclusions: Internal hex platform-switched implants placed equicrestally and restored with 1-mm abutments presented greater marginal bone loss than identical implants with 3-mm abutments, with vertical mucosal thickness having no significant influence. Keywords: abutment height; marginal bone loss; platform switching; vertical mucosal thickness.

2020 - Minimally Invasive Management of Implant-Supported Rehabilitation in the Posterior Maxilla, Part I. Sinus Floor Elevation: Biologic Principles and Materials [Articolo su rivista]
Stacchi, Claudio; Spinato, Sergio; Lombardi, Teresa; Bernardello, Fabio; Bertoldi, Carlo; Zaffe, Davide; Nevins, Myron
abstract

Alveolar bone resorption and maxillary sinus pneumatization occurring after dental extraction in the posterior region of the maxilla may be problematic when planning implant-supported rehabilitation. Various regenerative options are available, including guided bone regeneration, bone block grafts, and lateral sinus augmentation. These procedures are associated with significant complication rates, high morbidity, increased therapy duration, and high cost. Less invasive approaches, such as transcrestal sinus floor elevation, and using short implants have been proposed in an attempt to reduce these drawbacks. The aim of this study is to analyze available evidence to suggest predictable options and identify minimally invasive management of implant-supported rehabilitation in the posterior maxilla. This article concerns biologic mechanisms regulating new bone formation after maxillary sinus augmentation and examines characteristics of available implants and grafting materials to help the clinician select the most rational and convenient surgical approach according to specific situations.

2020 - Minimally Invasive Management of Implant-Supported Rehabilitation in the Posterior Maxilla, Part II. Surgical Techniques and Decision Tree [Articolo su rivista]
Stacchi, Claudio; Spinato, Sergio; Lombardi, Teresa; Bernardello, Fabio; Bertoldi, Carlo; Zaffe, Davide; Nevins, Myron
abstract

Insufficient crestal bone is a common feature encountered in the edentulous posterior maxilla due to atrophy of the alveolar ridge and maxillary sinus pneumatization. Numerous surgical techniques, grafting materials, and timing protocols have been proposed for implant-supported rehabilitation of posterior maxillae with limited bone height. In the majority of potential implant sites, residual bone height is less than 8 mm and the clinician has to select either a lateral or transcrestal sinus-elevation technique or placing short implants as the correct surgical option. Nevertheless, guidelines for selecting the best option remains mostly based on the personal experience and skills of the surgeon. The role of sinus anatomy in healing and graft remodeling after sinus floor augmentation is crucial. In addition to the evaluation of residual bone height, the clinician should consider that histologic and clinical outcomes are also influenced by the buccal-palatal bone wall distance. Therefore, three main clinical scenarios may be identified and treated with either a lateral or transcrestal sinus-elevation technique or short implants. This article introduces a new decision tree for a minimally invasive approach based on current evidence to help the clinician safely and predictably manage implant-supported treatment of the atrophic posterior maxilla.

2019 - A new histological method to study oral soft tissue penetrability to iodine and optimize oral use of iodine solutions [Articolo su rivista]
Zaffe, D; Spinato, S; Bertoldi, C
abstract

The aim of this work is to establish a histological method to fix iodine inside slides of treated oral mucosa more permanently in order to allow section counterstaining and facilitate improved clinical and experimental studies on iodine penetration. Transforming iodine into a stable histological formation inside tissues is particularly useful for histological analysis of clinical and experimental iodine treatments. In the field of oncology, this method can be applied to povidone-iodine-treated (human or animal) mucosa or skin, to organs treated with iodine tincture or Lugol’s solution, to oral lesion detection and to mucogingival junction identification.

2019 - Biological width establishment around dental implants is influenced by abutment height irrespective of vertical mucosal thickness: A cluster randomized controlled trial [Articolo su rivista]
Spinato, S.; Stacchi, C.; Lombardi, T.; Bernardello, F.; Messina, M.; Zaffe, D.
abstract

Objective: Prosthetic abutment height and peri-implant mucosal thickness are considered factors that influence marginal bone remodeling during biological width establishment around dental implants. However, no clinical studies have evaluated their simultaneous effect on marginal bone loss (MBL). This study analyzes the influence of abutment height on MBL around implants surrounded by both thin and thick mucosa up to 12 months after prosthetic loading. Material and methods: Seventy platform-switched implants with internal hex were placed equicrestally in two groups of patients with different vertical mucosal thickness: thin (≤2.0 mm) and thick mucosa (>2.0 mm). After three months of submerged healing, prosthetic abutments with a height of 1 mm (short) or 3 mm (long) were randomly assigned for single crown screwed restoration in both groups. MBL was evaluated on radiographs taken at implant placement (T 0 ), restoration delivery (T 1 ), and after 6 months (T 2 ) and 12 months (T 3 ) of loading. Results: After 12 months of loading, 66 implants were functioning (two dropouts, two failures), resulting in a 97% survival rate. Compared with T 0 , mean MBL at T 3 ranged between 0.59 and 0.80 mm in short abutment groups and between 0.28 and 0.37 mm in long abutment groups. Differences resulted statistically significant, irrespective of vertical peri-implant mucosal thickness. The MBL pattern over time showed the greatest amount of bone resorption in the first 6 months after loading, particularly around implants with short abutments. Conclusions: Platform-switched implants restored with short abutments present greater marginal bone loss than identical implants with long abutments, without significant peri-implant mucosal thickness effects.

2019 - Mechanisms of Hydrogen Sulfide against the Progression of Severe Alzheimer’s Disease in Transgenic Mice at Different Ages [Articolo su rivista]
Vandini, Eleonora; Ottani, Alessandra; Zaffe, Davide; Calevro, Anita; Canalini, Fabrizio; Cavallini, Gian Maria; Rossi, Rosario; Guarini, Salvatore; Giuliani, Daniela
abstract

Abstract Backgroud: Alzheimer disease is an age-related severe neurodegenerative pathology. The level of the third endogenous gas, hydrogen sulfide (H2S), is decreased in the brain of Alzheimer’s disease (AD) patients compared with the brain of the age-matched normal individuals; also, plasma H2S levels are negatively correlated with the severity of AD. Recently, we have demonstrated that systemic H2S injections are neuroprotective in an early phase of preclinical AD. Objectives: This study focuses on the possible neuroprotection of a chronic treatment with an H2S donor and sulfurous water (rich of H2S) in a severe transgenic 3×Tg-AD mice model. Method: 3×Tg-AD mice at 2 different ages (6 and 12 months) were daily treated intraperitoneally with an H2S donor and sulfurous water (rich of H2S) for 3 months consecutively. We investigated the cognitive ability, brain morphological alterations, amyloid/tau cascade, excitotoxic, inflammatory and apoptotic responses. Results: Three months of treatments with H2S significantly protected against impairment in learning and memory in a severe 3×Tg-AD mice model, at both ages studied, and reduced the size of Amyloid β plaques with preservation of the morphological picture. This neuroprotection appeared mainly in the cortex and hippocampus, associated with reduction in activity of c-jun N-terminal kinases, extracellular signal-regulated kinases and p38, which have an established role not only in the phosphorylation of tau protein but also in the inflammatory and excitotoxic response. Conclusion: Our findings indicate that appropriate treatments with various sources of H2S, might represent an innovative approach to counteract early and severe AD progression in humans.

2018 - Are periodontal outcomes affected by personality patterns? A 18-month follow-up study [Articolo su rivista]
Bertoldi, Carlo; Venuta, Marco; Guaraldi, Gianpaolo; Lalla, Michele; Guaitolini, Stefania; Generali, Luigi; Monzani, Daniele; Cortellini, Pierpaolo; Zaffe, Davide
abstract

OBJECTIVES: This research aims to study the relationship between personality traits and periodontal clinical outcomes by taking into account the level of anxiety and depression, periodontal health and oral hygiene behaviour of patients affected with gingivitis or moderate periodontitis requiring periodontal therapy. MATERIAL AND METHODS: The periodontal data of 40 systemically healthy patients affected by gingivitis or moderate periodontitis were collected at baseline and 18 months later. The psychological variables, dental awareness and adherence intent of the patients were assessed through questionnaires, and only those patients that exhibited a higher degree of compliance were included in the study. The personality traits (cluster A: paranoid, schizoid, schizotypal; cluster B: borderline, antisocial, narcissistic, and histrionic; cluster C: avoidant, dependent, and obsessive-compulsive) and the level of anxiety and depression of the patients were assessed. Patients were instructed with oral hygiene measures and were treated with periodontal therapy. RESULTS: Clusters A and B showed a consistent tendency for reduced levels of oral hygiene (increased full-mouth plaque score - FMPS). The results from cluster B were found to be significantly related to deep periodontal pockets at baseline. On the contrary, cluster C seemed to be linked to clinically better indices, particularly in terms of full-mouth-bleeding-score and pocket depth, both at baseline and 18 months later. The results collected from clusters B and C were directly correlated with anxiety, depression and FMPS. Moreover, anxiety was directly correlated with the patient's need for professional oral-care. CONCLUSIONS: Personality traits appear to play a significant role in determining the therapeutic outcomes of periodontal therapy in themselves. Thus, it is ideal for several important psychological, affective or behavioural factors to be associated with various personality traits so as to orient the outcome of periodontal therapy.

2018 - Bone regeneration by novel bioactive glasses containing strontium and/or magnesium: A preliminary in-vivo study [Articolo su rivista]
Bellucci, Devis; Cannillo, Valeria; Anesi, Alexandre; Salvatori, Roberta; Chiarini, Luigi; Manfredini, Tiziano; Zaffe, Davide
abstract

In this work, a set of novel bioactive glasses have been tested in vivo in an animal model. The new compositions, characterized by an exceptional thermal stability and high in vitro bioactivity, contain strontium and/or magnesium, whose biological benefits are well documented in the literature. To simulate a long-term implant and to study the effect of the complete dissolution of glasses, samples were implanted in the mid-shaft of rabbits' femur and analyzed 60 days after the surgery; such samples were in undersized powder form. The statistical significance with respect to the type of bioactive glass was analyzed by Kruskal-Wallis test. The results show high levels of bone remodeling, several new bone formations containing granules of calcium phosphate (sometimes with amounts of strontium and/or magnesium), and the absence of adverse effects on bone processes due to the almost complete glass dissolution. In vivo results confirming the cell culture outcomes of a previous study highlighted that these novel bioglasses had osteostimulative effect without adverse skeletal reaction, thus indicating possible beneficial effects on bone formation processes. The presence of strontium in the glasses seems to be particularly interesting.

2018 - Gingival tissue reaction to direct adhesive restoration: A preliminary study [Articolo su rivista]
Bertoldi, C.; Zaffe, D.; Generali, L.; Lucchi, A.; Cortellini, P.; Monari, E.
abstract

Introduction: It is debated whether composite resin marginal/submarginal direct restoration can be usefully performed without inflammatory consequences. This histological study is the first human analysis aimed to compare, in the same tooth, the gingival tissue close to composite resin restorations with gingival tissue close to hard tissue. Methods: Eight healthy patients with almost a residual strategic tooth needing endodontic therapy, and post-and-core restoration, then indirect prosthetic restoration, were selected. Direct margin relocation with composite resin was necessary to perform endodontic treatment. The crown lengthening with a secondary flap harvested was necessary to perform prosthetic rehabilitation. Three months after marginal relocation, the secondary flap was harvested, embedded in PMMA, 4-μm sectioned, and stained to analyze the inflammation degree. Results: All patients completed post-and-core reconstruction and the planned prosthetic therapy, maintaining the stringent hygienic protocol plan. The inflammation level comparison, slightly lower in gingiva close to the teeth (3.62 ± 0.38) than in gingiva close to the composite (3.75 ± 0.26), results in a p-value of 0.11 after Wilcoxon test. Conclusions: Results highlight a minimal, statistically not significant difference in the inflammation degree after margin relocation, conceivably due to patients, teeth and cases selection, together with adopted stringent methodological and supportive measures.

2018 - Minimum Abutment Height to Eliminate Bone Loss: Influence of Implant Neck Design and Platform Switching [Articolo su rivista]
Spinato, Sergio; Galindo Moreno, Pablo; Bernardello, Fabio; Zaffe, Davide
abstract

PURPOSE: This retrospective study quantitatively analyzed the minimum prosthetic abutment height to eliminate bone loss after 4.7-mm-diameter implant placement in maxillary bone and how grafting techniques can affect the marginal bone loss in implants placed in maxillary areas. MATERIALS AND METHODS: Two different implant types with a similar neck design were singularly placed in two groups of patients: the test group, with platform-switched implants, and the control group, with conventional (non-platform-switched) implants. Patients requiring bone augmentation underwent unilateral sinus augmentation using a transcrestal technique with mineralized xenograft. Radiographs were taken immediately after implant placement, after delivery of the prosthetic restoration, and after 12 months of loading. RESULTS: The average mesial and distal marginal bone loss of the control group (25 patients) was significantly more than twice that of the test group (26 patients), while their average abutment height was similar. Linear regression analysis highlighted a statistically significant inverse relationship between marginal bone loss and abutment height in both groups; however, the intercept of the regression line, both mesially and distally, was 50% lower for the test group than for the control group. The marginal bone loss was annulled with an abutment height of 2.5 mm for the test group and 3.0 mm for the control group. No statistically significant differences were found regarding marginal bone loss of implants placed in native maxillary bone compared with those placed in the grafted areas. CONCLUSION: The results suggest that the shorter the abutment height, the greater the marginal bone loss in cement-retained prostheses. Abutment height showed a greater influence in platform-switched than in non-platform-switched implants on the limitation of marginal bone loss.

2017 - Effects of COX1-2/5-LOX blockade in Alzheimer transgenic 3xTg-AD mice [Articolo su rivista]
Bitto, Alessandra; Giuliani, Daniela; Pallio, Giovanni; Irrera, Natasha; Vandini, Eleonora; Canalini, Fabrizio; Zaffe, Davide; Ottani, Alessandra; Minutoli, Letteria; Rinaldi, Mariagrazia; Guarini, Salvatore; Squadrito, Francesco; Altavilla, Domenica
abstract

Objective and design: Alzheimer’s disease (AD) is associated with amyloid plaques (Aβ) and hyperphosphorylated tau protein tangles in the brain. We investigated the possible neuroprotective role of flavocoxid, a dual inhibitor of cyclooxygenases-1/2 (COX-1/2) and 5-Lipoxygenase (5-LOX), in triple-transgenic (3xTg-AD) mice. Subjects: Mice were 3 months at the beginning of the study. Treatment: Animals received once daily for 3-month saline solution or flavocoxid (20 mg/kg/ip). Methods: Morris water maze was used to assess learning and memory. Histology was performed to evidence Aβ plaques and neuronal loss, while inflammatory proteins were determined by western blot analysis. Results: Saline-treated 3xTg-AD mice showed an impairment in spatial learning and memory (assessed at 6 months of age), and increased expression of inflammatory and apoptotic molecules. Treatment of 3xTg-AD mice with flavocoxid reduced: (1) learning and memory loss; (2) the increased eicosanoid production and the phosphorylation level of amyloid precursor protein (APP-pThr668), Aβ 1–42, p-tau (pThr181), pERK, and the activation of the NLRP3 inflammasome; (3) Aβ plaques; and (4) neuronal loss, compared to saline-treated animals. Conclusions: Pharmacological blockade of both COX-1/2 and 5-LOX was able to counteract the progression of AD by targeting pathophysiological mechanisms up- and downstream of Aβ and tau.

2017 - How Intraday Index Changes Influence Periodontal Assessment: A Preliminary Study [Articolo su rivista]
Bertoldi, Carlo; Forabosco, Andrea; Lalla, Michele; Generali, Luigi; Zaffe, Davide; Cortellini, Pierpaolo
abstract

It is reputed that periodontal indices remain unchanged over a 24-hour period, with great clinical significance. This preliminary study analyzes daily index changes. In 56 selected patients, full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), periodontal screening and recording (PSR) indices, and periodontal risk assessment (PRA) were recorded at baseline and three times per day (check-I: 08.30, check-II: 11.30, and check-III: 14.30), after appropriate cause-related therapy. Correlation between variables was statistically analyzed by Stata. All periodontal indices improved at the examination phase. Statistical differences were detected for FMPS comparing all thrice daily checks. Statistical differences were detected for FMBS and PRA comparing check-III with check-I and check-II. PSR showed no significant changes. The worst baseline indices produced the widest daily fluctuation at the examination phase. Significant variation of indices is directly related to clinical severity of periodontal conditions at baseline. Patients affected by severe periodontal disease may show significantly greater index changes. As indices are routinely recorded only once per day, the index daily variation has clinical significance. This greatly affects therapeutic strategy as correct periodontal assessment requires multiple evaluations at standardized times, particularly when baseline conditions are severe.

2017 - Hybrid and fully-etched surface implants in periodontally healthy patients: A comparative retrospective study on marginal bone loss [Articolo su rivista]
Spinato, Sergio; Bernardello, Fabio; Sassatelli, Paolo; Zaffe, Davide
abstract

Background: Human studies on implants with the same design but with different surfaces are lacking at the present time. Purpose: The aim of this study was to compare the survival rate of and marginal bone loss (MBL) around 2 types of implants with the same design, but with different surfaces: fully "sandblasted and double-etched" (SDE) implants and hybrid (H) implants, with an apical SDE-surface and a coronal machined-surface. Materials and methods: The SDE- and H-surfaces were previously analyzed under SEM and profilometer. Implants were placed in partially edentulous periodontally healthy patients requiring single implant-restoration, in either mandible or maxilla, with cement-retained prosthetic restoration. Twelve months after prosthetic loading, MBL in relation to prosthetic abutment height (AH), calculated radiographically, was statistically analyzed. Results: SEM and profilometer analyses revealed no differences between the SDE-surfaces of either SDE- or H-implants. Transverse ridges and grooves characterized the machined portion of H-implants, clearly influencing the profilometer analysis. In 75 patients, 37 SDE and 38 H-implants were placed and all functioned completely after 12 months. In both SDE- and H-groups, MBL had a significant inverse relationship with AH, with greater intercept and negative slope for SDE-group and intersection of the 2 regression lines at AH=2 mm. Conclusions: A 100% survival rate was recorded for SDE- and H-implants placed in pristine bone of periodontally healthy patients; MBL was limited and similar in both SDE- and H-groups; the higher the prosthetic AH, the lesser the MBL around implants; H-implants could reduce bone loss most effectively with abutments lower than 2 mm, realistically exploitable on thin biotypes; SDE-implants could reduce bone loss most effectively with abutments greater than 2 mm, realistically exploitable on thick biotypes.

2017 - Hybrid Implants in Healthy and Periodontally Compromised Patients: A Preliminary Clinical and Radiographic Study [Articolo su rivista]
Spinato, Sergio; Bernardello, Fabio; Sassatelli, Paolo; Zaffe, Davide
abstract

This preliminary clinical and radiographic study examined the survival of, the marginal bone loss (MBL) around, and the influence of prosthetic abutment height (AH) on MBL around hybrid implants placed in two groups of partially edentulous patients: healthy (HPs) and periodontally compromised (PCPs) patients. A total of 93 patients requiring single or multiunit implant restoration, in the mandible or maxilla, were treated while undergoing cement-retained prosthetic restoration. A total of 54 implants (35 in the maxilla and 19 in the mandible) were placed in 45 HPs, and 56 implants (31 in the maxilla and 25 in the mandible) in 48 PCPs. All 110 hybrid implants positioned in pristine bone provided a 100% survival rate in both HPs and PCPs. No statistical differences were recorded comparing the MBL values of maxillae with those of mandibles. In HPs and PCPs, a similar and limited amount of MBL was recorded, and it was found that the higher the AH, the less MBL. In conclusion, results indicate that the hybrid implants examined could reduce the risk of peri-implantitis due to their coronal machined surfaces and improve osseointegration due to their apical rough surfaces.

2017 - Impianti ibridi in pazienti sani e parodontalmente compromessi: studio clinico e radiografico preliminare [Articolo su rivista]
Spinato, Sergio; Bernardello, Fabio; Sassatelli, Paolo; Zaffe, Davide
abstract

Questo studio clinico e radiologico preliminare ha esaminato la sopravvivenza, la perdita di osso marginale (MBL) e l’influenza dell’altezza dell’abutment protesico (AH) sulla MBL intorno a impianti ibridi posizionati in due gruppi di pazienti parzialmente edentuli: pazienti parodontalmente sani (HP) e parodontalmente compromessi (PCP). In totale, sono stati trattati 93 pazienti che necessitavano di restauri implantari singoli o multipli, in entrambe le arcate, con applicazione di restauri protesici cementati. Sono stati posizionati 54 impianti (35 nell’arcata superiore e 19 in quella inferiore) in 45 HP e 56 impianti (31 nell’arcata superiore e 25 in quella inferiore) in 48 PCP. Tutti i 110 impianti ibridi posizionati in osso intatto hanno fatto registrare una percentuale di sopravvivenza del 100% sia negli HP sia nei PCP. Non sono state registrare differenze statistiche nel confronto dei valori di MBL dell’arcata superiore con quelli dell’arcata inferiore. In HP e PCP, è stata registrata una quantità similare e limitata di MBL ed è stato trovato che maggiore era l’AH, minore era la MBL. In conclusione, i risultati indicano che gli impianti ibridi esaminati possono ridurre il rischio di perimplantite dovuta alla superfici coronali macchinate e migliorare l’osteointegrazione grazie alle loro superfici apicali ruvide.

2017 - Multiple beneficial effects of melanocortin MC4 receptor agonists in experimental neurodegenerative disorders: Therapeutic perspectives [Articolo su rivista]
Giuliani, Daniela; Ottani, Alessandra; Neri, Laura; Zaffe, Davide; Grieco, Paolo; Jochem, Jerzy; Cavallini, Gian Maria; Catania, Anna; Guarini, Salvatore
abstract

Melanocortin peptides induce neuroprotection in acute and chronic experimental neurodegenerative conditions. Melanocortins likewise counteract systemic responses to brain injuries. Furthermore, they promote neurogenesis by activating critical signaling pathways. Melanocortin-induced long-lasting improvement in synaptic activity and neurological performance, including learning and memory, sensory-motor orientation and coordinated limb use, has been consistently observed in experimental models of acute and chronic neurodegeneration. Evidence indicates that the neuroprotective and neurogenic effects of melanocortins, as well as the protection against systemic responses to a brain injury, are mediated by brain melanocortin 4 (MC4) receptors, through an involvement of the vagus nerve. Here we discuss the targets and mechanisms underlying the multiple beneficial effects recently observed in animal models of neurodegeneration. We comment on the potential clinical usefulness of melanocortin MC4 receptor agonists as neuroprotective and neuroregenerative agents in ischemic stroke, subarachnoid hemorrhage, traumatic brain injury, spinal cord injury, and Alzheimer's disease.

2017 - The maintenance of inserted titanium implants: in-vitro evaluation of exposed surfaces cleaned with three different instruments [Articolo su rivista]
Bertoldi, Carlo; Lusuardi, Donatella; Battarra, Francesca; Sassatelli, Paolo; Spinato, Sergio; Zaffe, Davide
abstract

Objective: Changes to titanium implants smooth-surfaces after instrumentation were comparatively analyzed using low-vacuum scanning electron microscopy (LV-SEM) and white-light confocal (WLC) profilometry, to accurately evaluate curved surfaces. Material and methods: Sixty titanium implants screwed to their abutments were randomly split into three groups for cleaning treatment with (S) stainless-steel Gracey-curettes, (T) titanium Langer-curettes, and (P) an ultrasonic-device with the probe covered with a plastic-tip. One sector of each implant was left unprocessed (U). The other sectors were cleaned for either 60 s, to simulate a single cleaning session, or 180 s to simulate a series of sessions. Surface morphology was analyzed by LV-SEM, without metal sputtering. Quantitative evaluations of the roughness of surfaces were performed using a WLC-profilometer. The Wilcoxon and the Mann-Whitney tests were used in statistical comparisons. Results: U-surfaces showed that thin transverse ridges and grooves, i.e. a polarized surface roughness was substantially compromised after S-instrumentation. Small surface alterations, increasing with time, were also recorded after T-·and·P-instrumentation, although to a lesser degree. The gap of the fixture-abutment connection appeared almost completely clean after T-, clotted with titanium debris after S-, and clotted with plastic debris after P-treatment. The mean roughness (Ra) was unchanged after P-, significantly increased after S- and decreased after T-treatment, when compared with U. The Rz roughness-parameter, calculated along the fixture Y-axis, of S, T, and P resulted similar and significantly lower than that of U. Rz (X-axis) resulted unchanged after P-, slightly increased (+40%) after T-, and greatly increased (+260%) after S-treatment, this latter being statistically significant when compared with U. Conclusions: The careful use of titanium-curettes could produce only minimal smooth surface alteration particularly over prolonged treatments, and avoid debris production that could endanger implant preservation.

2016 - Attendibilità della tomografia computerizzata a fascio conico nella valutazione del tessuto mineralizzato nei rialzi di seno [Articolo su rivista]
Soardi, Carlo Maria; Suárez López del Amo, Fernando; Galindo Moreno, Pablo; Catena, Andrés; Zaffe, Davide; Wang, Hom Lay
abstract

Scopo: l’obiettivo dello studio era l’analisi delle densitometrie della tomografia computerizzata a fascio conico (CBCT) di rialzi di seno mascellari utilizzando osso omologo, utilizzando anche campioni microradiografici ottenuti precedentemente per verificare il potenziale diagnostico della CBCT. Materiali e metodi: è stato utilizzato un protocollo a due fasi in 21 pazienti consecutivi, tutti con un’altezza di osso crestale < 2 mm. Il rialzo di seno è stato effettuato con granuli di osso omologo mineralizzato con accesso laterale. È stata eseguita una serie di scansioni CBCT della mascella prima delle chirurgia, immediatamente dopo il rialzo del seno mascellare e dopo 6, 10 e 18 mesi dal posizionamento implantare. Mediante sonde virtuali, le immagini CBCT acquisite a 6, 8 e 10 mm dalla superficie crestale sono state processate con un software di imaging medicale ed espresse come livelli di grigio (LG). Risultati: in totale, sono state eseguite 24 procedure di incremento di seno in 21 pazienti. I valori medi di CBCT-LG variavano da 571 a 654, presentando il valore massimo a 8 mm immediatamente dopo il posizionamento implantare e il valore minimo a 6 mm dopo 10 mesi. Inoltre, è stato rilevato che il contenuto minerale dell’innesto diminuiva nel tempo, scomparendo completamente tra 10 e 11 mesi. Conclusione: La CBCT e il software di imaging medicale utilizzati per la visualizzazione e l’analisi delle immagini sono strumenti affidabili per studiare il comportamento dei biomateriali dopo le procedure di rialzo di seno. Inoltre, i risultati di questo studio dimostrano che è possibile un completo riassorbimento dell’alloinnesto di osso umano. A causa della dimensione limitata del campione, sono ecessari ulteriori studi morfometrici e clinici.

2016 - Piezosurgical treatment of crestal bone: quantitative comparison of post-extractive socket outcomes with those of traditional treatment [Articolo su rivista]
Spinato, Sergio; Rebaudi, Alberto; Bernardello, Fabio; Bertoldi, Carlo; Zaffe, Davide
abstract

ObjectiveThe study aimed to quantitatively compare, for the first time, the clinical outcomes of crestal bone volume resorption in sockets undergoing traditional extraction technique (TET) or piezosurgical extraction technique (PET), also considering the influence of buccal plate thickness. Material and methodsIn this prospective study, 19 sockets were randomly treated with TET, and 18 sockets were randomly treated with PET. Furthermore, patients were split into subgroup A, with buccal bone plate thickness (BPT) 1mm, and subgroup B, with BPT>1mm. Buccal (BCH) and palatal (PCH) cortex height, bucco-palatal ridge (BPR) width were monitored at tooth extraction and after the 4-month post-extractive period of natural healing. ResultsAfter 4months, BCH, PCH and BPR width decreased more in the TET than in the PET group, but only the BPR decrease was statistically significant (P=0.034) after ANOVA test. In both TET and PET groups, all B subgroup patients showed a lower decrease than A subgroup patients for both BCH, PCH and BPR, statistically significant for PCH (P=0.019) and BPR (P<0.001) of TET group, and BPR (P=0.002) of PET group, after ANOVA. Both A and B subgroups of PET showed a statistically significant lower decrease than the corresponding subgroups of TET, comparing A (P=0.005) and B (P=0.037) subgroups for BPR, after ANOVA. ConclusionsWith both thin and thick buccal plates, the piezosurgical extraction technique of teeth significantly decreases the horizontal resorption of the hard tissue ridge, but not the vertical resorption. Moreover, buccal plate thickness seems to be a key factor in post-extractive bone resorption: the thinner the buccal plate the greater the horizontal crestal bone loss.

2016 - Reliability of Cone Beam Computed Tomography in Determining Mineralized Tissue in Augmented Sinuses [Articolo su rivista]
Soardi, Carlo Maria; Suárez López Del Amo, Fernando; Galindo Moreno, Pablo; Catena, Andrés; Zaffe, Davide; Wang, Hom Lay
abstract

PURPOSE: The aim of this study was to analyze cone beam computed tomography (CBCT) densitometries of maxillary sinuses augmented with human bone allograft. In addition, previously obtained microradiographic specimens were used to verify the diagnostic potential of CBCT. MATERIALS AND METHODS: A two-stage protocol was conducted in 21 consecutive patients, all with a crestal bone height < 2 mm. Mineralized human bone allograft particles were used to augment sinuses using a lateral window approach. A succession of CBCT scans of the maxilla were taken before surgery, immediately after sinus augmentation, and 6, 10, and 18 months after implant placement. Using virtual probes, CBCT images taken at 6, 8, and 10 mm from the crestal surface were processed with medical imaging software and expressed as gray level (GL). RESULTS: A total of 24 sinus augmentation procedures were performed in 21 patients. The average values of CBCT-GL ranged from 571 to 654, presenting the maximum value at 8 mm immediately after implant placement and the minimum value at 6 mm after 10 months. Furthermore, it was found that the graft mineral content decreased over time, completely disappearing between 10 and 11 months. CONCLUSION: CBCT and the medical imaging software employed for imaging visualization are reliable tools to study biomaterial behavior after sinus augmentation procedures. In addition, results from this study demonstrate that a complete resorption of human bone allograft is possible. Due to the limited sample size, further clinical and morphometric studies are needed.

2015 - Analysis of protein expression in periodontal pocket tissue: a preliminary study [Articolo su rivista]
Monari, Emanuela; Cuoghi, Aurora; Bellei, Elisa; Bergamini, Stefania; Lucchi, Andrea; Tomasi, Aldo; Cortellini, Pierpaolo; Zaffe, Davide; Bertoldi, Carlo
abstract

The periodontal disease is caused by a set of inflammatory disorders characterized by periodontal pocket formation that lead to tooth loss if untreated. The proteomic profile and related molecular conditions of pocket tissue in periodontally-affected patients are not reported in literature. To characterize the proteomic profile of periodontally-affected patients, their interproximal periodontal pocket tissue was compared with that of periodontally-healthy patients. Pocket-associated and healthy tissue samples, harvested during surgical therapy, were treated to extract the protein content. Tissues were always collected at sites where no periodontal-pathogenic bacteria were detectable. Proteins were separated using two-dimensional gel electrophoresis and identified by liquid chromatography/mass spectrometry. After identification, four proteins were selected for subsequent Western Blot quantitation both in pathological and healty tissues.

2015 - Changes in thickness of mucosa adjacent to implants using tissue matrix allograft: A clinical and histologic evaluation [Articolo su rivista]
Farina, Vittorio; Zaffe, Davide
abstract

PURPOSE: To clinically and histologically evaluate the soft tissue thickening seen on acellular human dermis grafting at implant placement, taking into consideration the biotype. MATERIALS AND METHODS: Mucosal thickness was measured before and 4 months after implant placement, when the thickness of the epithelium and corium and the inflammation were histologically evaluated with a skin biopsy. Results were analyzed using the Mann-Whitney U test and linear regression analysis. RESULTS: In a total of 47 implant sites (22 uncovered and 25 covered by the allograft matrix), the grafted sites showed a significantly greater increase in thickness compared with the control sites. Histology was unable to show differences between groups. Nevertheless, using an individual variation index involving the histologic and initial clinical thickness, the increase in thickness of grafted sites was statistically significant (P = .017) compared with the decrease in control sites. Furthermore, the greatest thickness increase was recorded in sites with thin biotype, whereas a decrement was found in control sites. The inflammation index was similar in both groups. CONCLUSION: This study demonstrated the effectiveness of evaluating the increase in mucosal thickness with acellular human dermis grafting, particularly in subjects with thin biotype.

2015 - Effects of soft-drinks and remineralising treatment on teeth assessed by morphological and quantitative X-ray investigations [Articolo su rivista]
Bertoldi, Carlo; Lucchi, A; Zaffe, Davide
abstract

AIM: To morphologically and chemical-physically analyse both the surface and the subsurface of enamel undergoing soft- drink demineralisation and remineralisation treatment. MATERIALS AND METHODS: Fifteen human premolars were split and immersed in saline or three popular soft drinks, as demineralising agent, 15 minutes per day, for seven days at room temperature. Half of drink-processed teeth was then treated with casein phosphopeptide-amorphous calcium phosphate, as remineralising agent, for an additional seven days. The surface morphology was evaluated by stereomicroscope and scanning electron microscope (SEM). Teeth were then re-embedded and sectioned, and analysed under SEM and X-ray microprobe. RESULTS: Drink-processed teeth showed root pigmentation, opacification and deterioration of the superficial enamel. The enamel surface resulted greatly furrowed after drink processing, and apparently restored after remineralising treatment. However, in tooth sections, SEM showed always a subsurface demineralisation of dentine and enamel, in particular at the cementoenamel junction, also after reminalising treatment. The remineralising agent produced a partial remineralisation of the subsurface enamel, sometimes statistically significant, but not in hydroxyapatite stoichiometry. CONCLUSION: Soft-drink erosion impaired not only the surface but also the subsurface enamel. The applied remineralising treatment, yielding some effects on surface and subsurface enamel reversing basically the decalcification process.

2015 - In vivo evaluation of gingival tissue reaction to composite resin restoration - a pilot study [Abstract in Atti di Convegno]
Bertoldi, Carlo; Martani, Marco; Battarra, Francesca; Cortellini, Pierpaolo; Zaffe, Davide
abstract

Composite cements are extensively used to treat crown and dental neck defect. One of the most important problem to know the successful usability of these materials almost in the coronal part of dental root. No information exists about the behavior of human gingival tissue close to these kind of materials. This study analyzes the reaction of the human gingival to composite build up performed in the dental neck area and the coronal part of the dental root. In 8 healthy patients with almost one tooth jeopardized at the neck/root zone and requiring endodontic detoxification therapy, and after crown lengthening surgical procedure to restore the physiological length of the biological space, composite build up (Esthet. X®) was necessary to ensure marginal tissue stability and secure dental dam apposition. During the crown lengthening, 3 months after the Esthet.X® build up, the econdary flap was harvested, fixed in buffered 4% paraformaldeyde, ethanol dehydrated and methyl methacrylate embedded. Three micron section were obtained from biopsies and the intensity of inflammation was evaluated after Gomori trichrome or hematoxilyn-eosin stain using a grade scale. The corion showed an uneven distribution of inflammatory cells, both in gingival close to the Esthet. X® restored portion and the tooth hard tissues. The inflammation grade varied from severe to weak. The statistical analysis performed using the Mann-Whitney test did not show any significant difference in the gingival tissue close to the restoration or hard tissue surface. Within the limitations of this pilot study, the results seem to indicate that use of this kind of composite does not so much greatly alter the gingival tissue, as the patient’s lifestyle or dental hygiene.

2015 - Maxillary sinus augmentation by crestal access: a retrospective study on cavity size and outcome correlation [Articolo su rivista]
Spinato, Sergio; Bernardello, Fabio; Galindo Moreno, Pablo; Zaffe, Davide
abstract

Objective: Cone-beam computed tomography (CBCT) and radiographic outcomes of crestal sinus elevation, performed using mineralized human bone allograft, were analyzed to correlate results with maxillary sinus size. Material and methods: A total of 60 sinus augmentations in 60 patients, with initial bone ≤5 mm, were performed. Digital radiographs were taken at surgical implant placement time up to post-prosthetic loading follow-up (12-72 months), when CBCT evaluation was carried out. Marginal bone loss (MBL) was radiographically analyzed at 6 months and follow-up time post-loading. Sinus size (BPD), implant distance from palatal (PID) and buccal wall (BID), and absence of bone coverage of implant (intra-sinus bone loss - IBL) were evaluated and statistically evaluated by ANOVA and linear regression analyses. Results: MBL increased as a function of time. MBL at final follow-up was statistically associated with MBL at 6 months. A statistically significant correlation of IBL with wall distance and of IBL/mm with time was identified with greater values in wide sinuses (WS ≥ 13.27 mm) than in narrow sinuses (NS < 13.27 mm). Conclusions: This study is the first quantitative and statistically significant confirmation that crestal technique with residual ridge height <5 mm is more appropriate and predictable, in terms of intra-sinus bone coverage, in narrow than in WS.

2015 - Melanocortins promote neurogenesis and counteract cognitive decline in a transgenic mouse model of moderate Alzheimer’s disease [Abstract in Rivista]
Neri, Laura; Canalini, Fabrizio; Calevro, Anita; Ottani, Alessandra; Vandini, Eleonora; Sena, Paola; Zaffe, Davide; Giuliani, Daniela; Guarini, Salvatore
abstract

Alzheimer's disease (AD), both sporadic and genetic, is a chronic disorder characterized by activation of the amyloid/tau cascade in the hippocampus and isocortex. Besides neuroprotective approaches, also neurorestorative strategies for AD are under intensive investigations. [1] The melanocortin system consists of endogenous neuropeptides of the adrenocorticotropin/melanocyte-stimulating hormone (ACTH/MSH) family, acting via five different metabotropic melanocortin receptor subtypes (MC1-MC5). Melanocortins also induce neuroprotection associated with long-lasting functional recovery and counteraction of cognitive decline, as found in acute experimental neurodegenerative conditions and more recently in a chronic neurodegenerative disease as AD. [2] Further, these endogenous peptides have been by us reported to stimulate neurogenesis in an acute neurodegenerative disorder as ischemic stroke. [3] Here we investigated the possible neuroprotective and neurogenic effect of melanocortins in AD with a medium level of severity by using 24 week-old (at the start of the study) APPSwe transgenic mice (Tg2576). METHODS: Tg2576 mice were treated (once daily on days 1-50) with a nanomolar dose of the melanocortin analog [Nle4,D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH). Animals were prepared for 5-bromo-2’-deoxyuridine (BrdU) labeling of proliferating cells at days 1-11 of the study, and histological and immunohistochemical studies of the brain were performed for the assessment of neurogenesis. Further, the mouse ability to learn and recall was evaluated by means of the Morris water-maze test at the twenty-seventh week (starting 14 days after the first BrdU injection) and thirty-first week of age. Within 90 min the end of the last behavioural test (day 50 of the study; 31 week-old mice) animals were killed and the brains were removed and processed for histological examination. The whole hippocampi were dissected from brains of some animals to perform western blot analysis of the Zif268 protein (Zif268 protein is transiently expressed after synaptic activation). All values were analyzed by means of two-way repeated measures ANOVA (behavioral data) or one-way ANOVA (all other data), both followed by the Student-Newman-Keuls’ test. A value of p < 0.05 was considered significant. RESULTS: Treatment of Tg2576 mice with the melanocortin analog [Nle4,D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH) reduced cerebral cortex/hippocampus level of Aβ deposit (p < 0.001), increased hippocampus Zif268 expression (p <0.001), improved brain histological picture and cognitive functions (p <0.001), relative to saline-treated Tg2576 animals, and no signs of toxicity were recorded. Further, immunohistochemical examination of the hippocampus on day 50 (end of the study) showed, in the dentate gyrus of NDP-α-MSH-treated Tg2576 mice, a very elevated number of BrdU immunoreactive cells colocalized with NeuN (indicator of mature neurons) and Zif268 (indicator of functionally integrated neurons), in comparison with saline-treated Tg2576 animals (p <0.001); no newly formed astrocytes were found. Animal pretreatment (before each administration of NDP-α-MSH) with the selective melanocortin MC4 receptor antagonist HS024 prevented all favourable effects of NDP-α-MSH (p <0.001). CONCLUSIONS: Our data suggest that MC4 receptor-stimulating melanocortins are able to counteract cognitive decline in experimental AD not only by affording neuroprotection, but also by inducing intense neurogenesis. These agents could be candidates for an innovative and safe strategy to counteract AD progression in humans.

2015 - NDP-α-MSH induces intense neurogenesis and cognitive recovery in Alzheimer transgenic mice through activation of melanocortin MC4 receptors [Articolo su rivista]
Giuliani, Daniela; Neri, Laura; Canalini, Fabrizio; Calevro, Anita; Ottani, Alessandra; Vandini, Eleonora; Sena, Paola; Zaffe, Davide; Guarini, Salvatore
abstract

Melanocortins exert neuroprotection in a variety of experimental neurodegenerative disorders, including Alzheimer's disease (AD). Further, in previous research we showed that these endogenous peptides stimulate neurogenesis in an acute neurodegenerative disorder such as ischemic stroke. In the present research, we investigated the potential neurogenic effect of melanocortins in AD using APPSwe transgenic mice (Tg2576). To this purpose, 24week-old animals were prepared for 5-bromo-2'-deoxyuridine (BrdU) labeling of proliferating cells on days 1-11 of the study. Treatment of Tg2576 mice with nanomolar doses of the melanocortin analog [Nle(4),D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH), administered once daily from day 1 to 50, improved brain histology and cognitive functions relative to saline-treated Tg2576 animals. No signs of toxicity were observed. Immunohistochemical examination of the hippocampus at the end of the study (day 50) showed that NDP-α-MSH-treated Tg2576 mice had a greater number of BrdU immunoreactive cells colocalized with NeuN (an indicator of mature neurons) and Zif268 (an indicator of functionally integrated neurons) in the dentate gyrus, relative to saline-treated Tg2576 animals; no newly formed astrocytes were found. Animal pretreatment with selective melanocortin MC4 receptor antagonist HS024 before each NDP-α-MSH administration prevented all the beneficial effects of the peptide. The present data indicate that MC4 receptor stimulation by a melanocortin prevents cognitive decline in experimental AD, this effect being associated not only with neuroprotection but also with an intense neurogenesis. MC4 receptor agonists could be innovative and safe candidates to counteract AD progression in humans.

2015 - On the Great Anatomists [Altro]
Zaffe, Davide
abstract

Anatomy handbook of great people

2015 - SEM AND PROFILOMETRIC ANALYSES OF SMOOTH SURFACES OF TITANIUM IMPLANTS CLEANED WITH 3 INSTRUMENTATIONS [Abstract in Atti di Convegno]
Battarra, Francesca; Bertoldi, Carlo; Ventura, Sara; Martani, Marco; Lusuardi, Donatella; Zaffe, Davide
abstract

Dental implants require regular maintenance of smooth surfaces. It’s crucial that the instrument used for clinic maintenance be able to remove ecosystems without causing damage to the implant surface. Several instrumentation may be useful for this maintenance, but studies of their effect are actually inconclusive. This study compares the effect of cleaning treatment of titanium implants using low-vacuum scanning electron microscopy (LV-SEM) and white-light confocal (WLC) profilometry to analyze curved surfaces. One sector of each titanium implants screwed to their abutments was left unprocessed (Us) or cleaned for 60 seconds, to simulate a single cleaning session, or for 180 seconds to simulate a series of sessions. Three types of instrumentation were randomly used on 60 implants: (Sc) stainless-steel Gracey curette; (Tc) titanium Langer curette; and (Pu) an ultrasonic device with the probe covered with a plastic tip. The morphology of the implant surfaces was analyzed by LV-SEM, without metal sputtering. Quantitative evaluations of the roughness of surfaces were then performed using a WLC-profilometer. The Kruskal-Wallis followed by the Dunn multiple comparison test were used in statistical comparisons. The unprocessed surfaces showed the presence of thin transverse ridges and grooves, i.e. a polarized surface roughness, being substantially compromised after Sc instrumentation. Small surface alterations, increasing with time, were also recorded after Tc and Pu instrumentation, lthough to a lesser degree. The gap of the fixture-abutment connection appeared almost completely clean after Tc, clotted with titanium debris after Sc, and with plastic debris after Pu treatment. The mean roughness (Ra) was nchanged after Pu, increased after Sc and decreased after Tc treatment, when compared with Us, but without statistical significance. The Rz roughness parameter, calculated along the fixture X-axis, was significantly greater after Sc treatment when compared with Us, Tc and Pu, whereas the differences between Tc, Pu and Us were not significant. All Rz roughness parameters of Sc, Tc and Pu, calculated along the fixture Y-axis, resulted almost identical and significantly lower than that of Us. Within the limitations of this study, a careful use of a titanium curette could produce a slight smooth surface alteration, particularly over prolonged treatments and may be more beneficial than the other treatments examined for stable ecosystem removal.

2015 - Stage Characterization and Marginal Bone Loss Evaluation Up to 96 Months of Crestal Sinus Augmentation With Sequential Drills: A Retrospective Study [Articolo su rivista]
Bernardello, Fabio; Felice, Pietro; Spinato, Sergio; Rebaudi, Alberto; Righi, Davide; Malagoli, Claudio; Torres Lagares, Daniel; Ruiz, Rafael Flores; Zaffe, Davide
abstract

Introduction: The 2-stage crestal approach to augment the maxillary sinus is a little-used technique. The aim of this retrospective study was to assess events characterizing stages of this technique after implant placement in the posterior maxilla with residual bone height less than 4 mm and evaluate the marginal bone loss (MBL) changes over time. Material and Methods: Thirty-three patients underwent unilateral sinus augmentations using the trancrestal technique with mineralized allograft. Six-months (6 m) after first surgery, if skeletal subsidence prevented insertion of a 10-mm-length implant, additional grafting was performed during implant (n = 33) insertion. Radiographs were taken before grafting (baseline), immediately after and at 6 months; immediately after and 6 months after implant placement; and at follow-up (24–96 m). Results: One implant was lost (ISR = 96.97%). Of the remaining 32 patients, 14 (A group) underwent standard implant placement, whereas 18 (B group) underwent additional grafting immediately before implant placement. Given that B-group patients initially obtained lower crestal bone height after first surgery, additional grafting procedures provided greater crestal height in the B group. A significant relationship between ending (eMBL) and 6mMBL was found in both groups, with greater values in the B group. However, in both groups, eMBL was always greater if 6mMBL was greater than 0.44 mm. Discussion: Results suggest a high and low skeletal-reactivity patient categorization. In both patient categories, MBL greatly depends upon 6-month values. Investigations are necessary to relate sinus size with results obtained by this 2-stage crestal approach. Conclusions: The 2-stage crestal sinus lift procedure not only provides predictable results, but also allows low skeletal-reactivity patient recovery.

2015 - The influence of composite resin restoration on gingival tissue: a pilot study [Abstract in Rivista]
Bertoldi, Carlo; Martani, M.; Generali, Luigi; Lucchi, A.; Zaffe, Davide; Consolo, Ugo
abstract

2014 - A Trabecular Metal Implant 4 Months After Placement: Clinical-Histologic Case Report [Articolo su rivista]
S., Spinato; Zaffe, Davide; P., Felice; L., Checchi; H., Wang
abstract

INTRODUCTION: The aim of this case report was to histologically evaluate the behavior of a trabecular metal (TM) implant composed of titanium and spatial 3-dimensional tantalum (Ta) trabeculae. This study is the first human histologic case report of this implant.; CASE PRESENTATION: A TM implant was placed in a 54-year-old woman exhibiting moderate chronic periodontitis. After periodontal treatment, the implant was inserted under favorable clinical conditions. Patient was not seen for 4 months because of unrelated breast reduction surgery. At the surgical reopening, periimplant inflammation affecting the coronal third of the implant was observed 4 months after implant placement. With patient's consent, the implant was removed for histologic analysis. Histology highlighted a greater amount of bone in close contact with Ta trabeculae than titanium surfaces.; CONCLUSION: The finding of bone formation around the Ta trabeculae suggests that trabecular metal material promotes bone ingrowth for secondary implant stability. Additional evidence is needed to confirm this observation.

2014 - An in vitro model of a system of electrical potential compensation in extracorporeal circulation. [Articolo su rivista]
Carletti, U.; Cattini, Stefano; Lodi, Renzo; Petralia, A.; Rovati, Luigi; Zaffe, Davide
abstract

OBJECTIVES: Extracorporeal circulation (ECC) in patients undergoing cardiac surgery induces systemic immune-inflammatory reaction that results in increased postoperative morbidity. Many factors are responsible for the adverse response after ECC. The present in vitro study aimed to investigate electric charges (ECs) generated during ECC, to set a device compensating the ECs, and checking its effect on red blood cells (RBC).; MATERIALS AND METHODS: The electrical signals of blood in ECC were collected by a custom developed low-noise electronic circuit, processed by a digital oscilloscope (DSO) and a dynamic signal analyzer (DSA). The compensation of ECs was performed using a compensation device, injecting a nulling charge into the blood circuit. The compensation effect of the ECs on RBCs was evaluated by scanning electron microscope (SEM).; RESULTS: The electrical analysis performed using both the DSO and the DSA confirmed the EC formation during ECC. The notable electric signals recorded in standard ECC circuits substantially nulled once the compensation device was used, thus confirming efficient EC compensation. After two hours of ECC, the SEM non-blended test on human RBC samples highlighted morphological changes in acanthocytes of the normal biconcave-shaped RBC.; CONCLUSIONS: The outcomes confirm the development of parasitic ECs during ECC and that a suppressor system may decrease the potential damage of ECs. Nevertheless, further studies are ongoing in order to investigate the complex mechanisms related to lymphocytes and platelet morphological and physiological chances during triboelectric charges in ECC.

2014 - Analisi tissutale proteomica della tasca parodontale. Uno studio pilota Periodontal pocket tissue analysis using proteome. A pilot study [Articolo su rivista]
Chiara, Pellacani; Monari, Emanuela; Zaffe, Davide; Cuoghi, Aurora; Bellei, Elisa; Andrea, Lucchi; Bergamini, Stefania; Tomasi, Aldo; Bertoldi, Carlo
abstract

Obbiettivo: Scopo dello studio è analizzare nello stesso soggetto, in siti in cui non erano rilevabili batteri parodontopatogeni, il tessuto inteprossimale, sia associato alla tasca parodontale sia sano, al fine di determinare un quadro proteico associabile al danno parodontale. Materiali & Metodi: Nello studio sono stati inclusi quindici soggetti sistemicamente sani, affetti da moderata-avanzata parodontite cronica, che presentavano almeno un difetto intraosseo prossimo ad un analogo sito senza danno parodontale clinicamente evidente. I pazienti sono stati trattati mediante terapia resettiva. Durante la fase chirurgica i tessuti associati alla lesione parodontale e quelli clinicamente sani sono stati prelevati per l’analisi proteomica. Risultati: Confrontando i profili proteici relativi al danno parodontale con quelli clinicamente sani, sono state identificate 19 proteine differentemente espresse. In particolare, in tutti i pazienti 8 proteine sono risultate sovra-espresse nel tessuto patologico (Anexina A2- ANX A2; Actina citoplasmatica 1 (spot 14 e 15)- ACTB; Anidrasi carbonica 1 - CAH1; Anidrasi carbonica 2- CAH2; Ig catena Kappa regione C (spot 17 e 18)- IGKC e flavina reduttasi- BLVRB) mentre 11 proteine sono risultate sotto-espresse (Tropomiosina catena -4- TPM3; proteina  14-3-3 - 1433S; proteina / 14-3-3 - 1433Z; -enolasi - ENOA; Heat shock proteina -1 (spot 5 e spot 6) - HSPB1; Triosofosfatoisomerasi - TPIS; Perossiredoxina-1 - PRDX1; Proteina epidermica legante acidi grassi - FABP5; Proteina S100-A9 - S10A9 e Galectina -7 - LEG7). Conclusioni: Dai dati preliminari ottenuti risulta evidenziata l’espressione differenziale, tra tessuto clinicamente sano e relativo al danno parodontale, di proteine che possono giocare un ruolo importante nella prevenzione del danno cellulare da stress, nella mediazione delle risposte immunitarie, nonché nei meccanismi di rigenerazione tissutale. Lo studio del profilo profilo proteomico del tessuto della tasca parodontale potrebbe essere cruciale sia per la conoscenza della patogenesi che per la terapia della malattia parodontale. Objective: To analyze in the same subject, in sites where no periodontopathogenic bacteria were detectable, pocket-associated and neighboring healthy interproximal tissues to qualify proteins associated with the periodontal damage. Matherials & Methods: Fifteen healthy patients, affected by moderate to advanced chronic periodontitis and presenting at least one intrabony defect and a neighboring not-damaged interproximal site were enrolled. Patients underwent osseous resective surgery. During surgery pocket-associated and clinically healthy tissues were harvested for proteomic analyses. Results: In both pocket-associated and clinically healthy tissues, nineteen differently expressed proteins were successfully identified. In particular, 8 proteins (Annexin A2; Actin cytoplasmic 1 (2 spots); Carbonic anhydrase 1; Carbonic anhydrase 2; Ig kappa chain C region (2 spots) and Flavinreductase) were over-expressed, while 11 proteins (Tropomyosin alpha-4 chain; 14-3-3 protein sigma; 14-3-3 protein zeta/delta; Alpha-enolase; Heat shock protein ß-1 (2 spots); Triosophosphateisomerase; Peroxiredoxin-1; Fatty acid-binding protein-epidermal; Protein S100-A9 and Galectin-7) were under-expressed in the pathological tissue of all patients. Conclusions: The preliminary data indicate differentially expression of proteins that may play important roles in the prevention of cellular damage by stress, in mediating the immune response as well as in tissue regeneration. The proteomic profile study of pocket tissue would be crucial both to appreciate the pathogenesis and the therapy of periodontitis.

2014 - Fresh-Frozen Bone Blocks for Horizontal Ridge Augmentation in the Upper Maxilla: 6-Month Outcomes of a Randomized Controlled Trial. [Articolo su rivista]
S., Lumetti; Consolo, Ugo; C., Galli; A., Multinu; L., Piersanti; Bellini, Pierantonio; E., Manfredi; G., Corinaldesi G; Zaffe, Davide; Gm, Macaluso; C., Marchetti
abstract

Purpose: This randomized controlled trial compared fresh-frozen versus autologous bone blocks for maxillary horizontal ridge augmentation in patients with Cawood and Howell class IV atrophies. Materials and Methods: Twenty-four patients were allocated to the autologous and fresh-frozen groups in a 1:1 ratio. Patients underwent computed tomography scans 1 week and 6 months after surgery for graft volume and density analysis. Doxycycline was administered at day 120 and day 150 to label new bone formation. Biopsy for histologic and histomorphometric analyses was performed at reentry for implant insertion, 6 months after grafting. Results: Fresh-frozen grafts had lower density than autologous bone. Autologous and fresh-frozen grafts lost, respectively, 25% and 52% of their initial volume (p=.0041). Histology revealed the presence of newly formed bone within both graft types, but clear signs of inflammation were present in fresh-frozen blocks. Conclusions: According to these 6-month results, autologous bone blocks are preferable to fresh-frozen bone grafts. © 2012 Wiley Periodicals, Inc.

2014 - Implant surface alterations following the use of three instrumentation systems: 1 - effects of a standard cleaning [Abstract in Rivista]
Bertoldi, Carlo; Battarra, F.; Lusuardi, D.; Giannetti, Luca; Generali, Luigi; Consolo, Ugo; Zaffe, Davide
abstract

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2014 - Implant surface alterations following the use of three instrumentation systems: 2 - simulation of an extended treatment [Abstract in Rivista]
Bertoldi, Carlo; Ventura, S.; Lusuardi, D.; Sassatelli, Paolo; Generali, Luigi; Giannetti, Luca; Consolo, Ugo; Zaffe, Davide
abstract

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2014 - Is socket healing conditioned by buccal plate thickness? A clinical and histologic study 4 months after mineralized human bone allografting. [Articolo su rivista]
S., Spinato; P., Galindo Moreno; Zaffe, Davide; F., Bernardello; Cm, Soardi
abstract

Objective: The aim of this study was to clinically and histologically analyze the healing of grafted sockets by mineralized human bone allograft (MHBA) and nongrafted sockets, correlating the results with buccal plate thickness. Material and methods: Thirty-one sockets were randomly split into control (CG) and treatment (MHBA grafted) (TG) groups and, subsequently, into four subgroups according to buccal plate thickness: a ≤ 1 mm and b > 1 mm. Ridge thickness, depth, and height were monitored. Four months after, at implant placement, a bone core biopsy for histologic and morphometric analyses was taken. Results: The differences of buccal height (TG-a -0.27 and CG-a -1.17 mm) and width (TG-a 0.55 and CG-a 2.67 mm, TG-b 0.12 and CG-b 1.17 mm) were statistically significant. The increase in bone amount CG-b (28.17%) compared with CG-a (16.98%) was statistically significant. Soft tissue amount of TG-b (54.21%) and TG-a (56.91%) was lower than that of CG-b (71.83%) and CG-a (83.01%), both being statistically significant (P = 0.002). Conclusions: The results proved that thin buccal plates had a worse outcome on socket healing and that network formation by MBHA not only predisposes a successful implant insertion but also acts as size keeper. © 2012 John Wiley & Sons A/S.

2014 - Melanocortins protect against brain damage and counteract cognitive decline in a transgenic mouse model of moderate Alzheimer׳s disease. [Articolo su rivista]
Giuliani, Daniela; Galantucci, M; Neri, L; Canalini, F; Calevro, Anita; Bitto, A; Ottani, Alessandra; Vandini, E; Sena, Paola; Sandrini, Maurizio; Squadrito, F; Zaffe, Davide; Guarini, Salvatore
abstract

We previously reported that melanocortins induce neuroprotection in experimental acute and chronic neurodegenerative conditions, including Alzheimer׳s disease (AD) of mild severity. Here we investigated whether melanocortins afford neuroprotection and counteract cognitive decline in AD with a medium level of severity by using 24 week-old (at the start of the study) APPSwe transgenic mice (Tg2576). Saline-treated (days 1-50) control Tg2576 mice showed an impairment in spatial learning and memory, associated (at day 50, end of the study) with hippocampus at low levels of the synaptic activity-dependent gene Zif268, relevant brain changes such as cerebral cortex/hippocampus increased level of β-amyloid (Aβ) deposit, and neuronal loss, in comparison with wild-type animals. Treatment of Tg2576 mice (once daily at days 1-50) with a nanomolar dose of the melanocortin analog [Nle4,D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH) reduced cerebral cortex/hippocampus level of Aβ deposit, decreased neuronal loss, increased hippocampus Zif268 expression and improved cognitive functions, relative to saline-treated Tg2576 mice. Pharmacological blockade of melanocortin MC4 receptors with the MC4 receptor antagonist HS024 prevented all favorable effects of NDP-α-MSH. Our data indicate that MC4 receptor-stimulating melanocortins are able to counteract cognitive decline in experimental AD of medium severity through induction of neuroprotection and improvement of synaptic transmission. After further studies, these agents could gain a role as disease modifying therapeutics for AD.

2014 - Melanocortins protect against progression of Alzheimer's disease in triple-transgenic mice by targeting multiple pathophysiological pathways [Articolo su rivista]
Giuliani, Daniela; A., Bitto; M., Galantucci; Zaffe, Davide; Ottani, Alessandra; N., Irrera; L., Neri; Cavallini, Gian Maria; D., Altavilla; A. R., Botticelli; F., Squadrito; Guarini, Salvatore
abstract

Besides specific triggering causes, Alzheimer's disease (AD) involves pathophysiological pathways that are common to acute and chronic neurodegenerative disorders. Melanocortins induce neuroprotection in experimental acute neurodegenerative conditions, and low melanocortin levels have been found in occasional studies performed in AD-type dementia patients. Here we investigated the possible neuroprotective role of melanocortins in a chronic neurodegenerative disorder, AD, by using 12-week-old (at the start of the study) triple-transgenic (3xTg-AD) mice harboring human transgenes APP(Swe), PS1(M146V), and tau(P301L). Treatment of 3xTg-AD mice, once daily until the end of the study (30 weeks of age), with the melanocortin analog [Nle(4),D-Phe(7)]-alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) reduced cerebral cortex/hippocampus phosphorylation/level of all AD-related biomarkers investigated (mediators of amyloid/tau cascade, oxidative/nitrosative stress, inflammation, apoptosis), decreased neuronal loss, induced over-expression of the synaptic activity-dependent gene Zif268, and improved cognitive functions, relative to saline-treated 3xTg-AD mice. Pharmacological blockade of melanocortin MC4 receptors prevented all neuroprotective effects of NDP-alpha-MSH. Our study identifies, for the first time, a class of drugs, MC4 receptor-stimulating melanocortins, that are able to counteract the progression of experimental AD by targeting pathophysiological mechanisms up- and down-stream of beta-amyloid and tau. These data could have important clinical implications. (C) 2014 Elsevier Inc. All rights reserved.

2014 - Microradiography and microcomputed tomography comparative analysis in human bone cores harvested after maxillary sinus augmentation: a pilot study. [Articolo su rivista]
Soardi, Cm; Clozza, E; Turco, G; Biasotto, M; Engebretson, Sp; Wang, Hl; Zaffe, Davide
abstract

OBJECTIVES: The aim of this study was to compare microradiography (MR) and microcomputed tomography (μCT) analysis of bone samples following maxillary sinus augmentation at different time periods and determine the relationships between measured area and volume fractions. MATERIALS AND METHODS: Lateral window sinus grafts were performed on 10 patients using a mineralized human bone allograft (MHBA). At implant placement, 5-13 months after surgery, 10 bone core biopsies were harvested. Prior to histologic sectioning, bone samples were evaluated with μCT. The morphometric parameters computed by MR and μCT were compared using Pearson's correlation and Bland and Altman analysis and included hard tissue fraction (HV/TV:%), soft tissue fraction (SV/TV:%), vital bone fraction (BV/TV:%) and residual graft fraction (GV/TV:%). RESULTS: Strong positive correlation between MR and μCT was found for HV/TV and SV/TV and BV/TV [r = 0.84, 0.84 and 0.69, respectively] but weak for GV/TV [r = 0.10]. CONCLUSION: μCT technology shows promising potential as an indicator of bone morphology changes; however, caution should be used in interpreting morphometric parameters, as the different methods reveal important biases.

2014 - Oral surgery biomaterials: analyses of Al2O3-treated titanium surfaces tested with fibroblast and osteocyte cell lines [Abstract in Rivista]
Smargiassi, Alberto; Ferretti, Marzia; Cavani, Francesco; Sena, Paola; Benincasa, Marta; Zaffe, Davide; Facciani, Valentino; Gabrel, Ivano; Palumbo, Carla
abstract

Two different cell lines - MLO-Y4 (murine osteocytes) and 293 (human fibroblasts) - cultured for 48 hours in standard media were used to analyse engineered bio-materials (i.e. Al2O3 shot-peened titanium surfaces). Distribution, density and expression of adhesion molecules (fibronectin and vitronectin) were evaluated under scanning electron microscope (SEM) and confocal microscope (CM) as previously described [1]. The engineered biomaterial surfaces showed under SEM irregular morphology displaying variously-shaped spicules, obtained by shooting different-in-size particles of Al2O3 against the scaffolds of biomaterial. DAPI and fluorochrome-conjugated antibodies were used to highlight nuclei, fibronectin and vitronectin, under CM; cell distribution was analysed after Gold-Palladium sputtering of samples by SEM. Both SEM and CM observations showed better outcome in terms of cell adhesion and distribution in treated titanium surfaces with respect to the untreated ones. The results obtained clearly showed that this kind of surface-treated titanium, used to manufacture devices for dental implantology: i) is very suitable for cell colonization, essential prerequisite for the best osseointegration, and ii) represents an excellent solution for the development of further engineered implants with the target to obtain recovery of dental function stable over time. Further studies on these Al2O3 shot-peened-titanium surfaces, both in vitro and in vivo, will be needed to obtain accurate definition of better biomaterial outcome, also after additional treatments. References [1] Palumbo et al. (2013) Immunocytochemical and structural comparative study of committed versus multipotent stem cells cultured with different biomaterials. Micron 47: 1–9.

2014 - Preliminary outcome in consecutively treated case series with trabecular metal implants [Articolo su rivista]
Soardi, Carlo Maria; Wang, Hom Lay; Clozza, Emanuele; Zaffe, Davide; Checchi, Luigi
abstract

Objective: The aim of this study was to illustrate the successful use of trabecular metal (TM) implants placed in posterior maxilla following maxillary sinus augmentation. Methods and Materials: Twelve TM implants were placed after maxillary sinus augmentation using mineralized human bone allograft (MHBA) in 6 patients. At second stage procedure, 3 months after TM implants installation, the outcome measures evaluated were implant success and removal torque test. Result: At second stage procedure, the implant success rate was 100%. No evidence of peri-implant marginal bone loss was noted clinically and all implants successfully tolerated a 25 Ncm torque test. Conclusions: The favorable outcome of the treatment described suggests that the rehabilitation of atrophic posterior maxillary region can be achieved by the placement of TM implants in sites augmented with MHBA.

2014 - Quantitative Comparison of Cone Beam Computed Tomography and Microradiography in the Evaluation of Bone Density after Maxillary Sinus Augmentation: A Preliminary Study. [Articolo su rivista]
Soardi, Cm; Zaffe, Davide; Motroni, A; Wang, H. L.
abstract

Purpose: Cone beam computed tomography (CBCT) and microradiographic analyses were comparatively performed in maxillary sinus augmentation to preliminarily verify the diagnostic potential of CBCT on the evaluation of bone regeneration. Materials and Methods: A two-stage protocol was conducted in 19 consenting patients, all having the crestal bone ≤2mm, in private dental office. Mineralized human bone allograft particles were used to augment sinus using lateral window approach. A succession of CBCT scans of the maxilla was taken before surgery, after sinus augmentation, and immediately after implant insertion. Using virtual probes, CBCT data were processed by medical imaging software and expressed as gray level (GL). A bone core biopsy was taken at implant placement, 6 months after surgery. Microradiography of transverse sections, taken 6, 8, and 10mm from the crestal surface, of methacrylate-embedded biopsies was performed to analyze and to evaluate the mineralized material amount (MM%). Results: A total of 21 sinus augmentations were performed. CBCT (mean GL: 646-693) data were not statistically different when comparing 6-, 8-, and 10-mm sites to after grafting/implant-insertion values. Furthermore, microradiographic (mean MM%: 45.3-48.3) data were not statistically different comparing 6-, 8-, and 10-mm sites, due to variation of values among patients. A GL and MM% parallelism was identified considering each patient, instead. A significant correlation (p<.001) between GL and MM% was found after both Wilcoxon test for paired data and simple linear regression analysis. Conclusions: The preliminary result clearly demonstrated the predictability of the CBCT analysis. Due to the limited sample and great variations of the MM% recorded in patients, further clinical and morphometric studies are needed to fulfill diagnostic expectations. © 2012 Wiley Periodicals, Inc.

2014 - Two-Stage Crestal Sinus Elevation by Sequential Drills in Less Than 4 mm of Residual Ridge Height [Articolo su rivista]
F., Bernardello; E., Massaron; S., Spinato; Zaffe, Davide
abstract

Purpose: The aim of this work, the first human histologic case report of this technique, was a clinical and histologic evaluation of implant placed in a severely atrophic maxilla using a 2-stage crestal sinus elevation. Case Presentation: A 52-year-old woman required rehabilitation of an atrophic maxilla with a fixed implant-supported prosthesis. At the first surgery, a crestal sinus lift was performed using beta-tricalcium phosphate (beta-TCP), as radiographic tracer, and mineralized human bone allograft (MHBA) as grafting material. After 6 months, a bone core biopsy was taken, and 2 implants were placed in the augmented sites. Four months later, implants were exposed, and 2 splinted gold-porcelain crowns were delivered. Histology highlighted basal bone disappearance, replaced by a wide composite network (similar to 50% vol/vol) of MHBA granules connected by newly formed bone, and osteoblastic activities. Conclusion: This case report demonstrates the possibility of executing a staged transcrestal sinus lift in atrophic situations. MHBA evidenced usefulness in maintaining bone volume. Histologic analyses confirmed the sound outcome of the graft augmentation. Additional studies would be beneficial to confirm or refute the reliability of this technique.

2014 - Use of Trabecular Metal Implants for the Rehabilitation of a Maxillary Edentulous Arch: A Case Report [Articolo su rivista]
Carlo Maria, Soardi; Emanuele, Clozza; Zaffe, Davide; Hom Lay, Wang
abstract

Introduction: This case report illustrates the use of trabecular metal (TM) implants to rehabilitate a severe atrophic maxillary arch that was successfully augmented by allografts. Case Presentation: A 68-year-old female was referred to a private practice for severe maxillary alveolar bone atrophy (e.g. subsinus bone height of <1 mm on left and <4 mm on the right side). Allograft bone block augmentation was employed to regenerate ridge deficiency simultaneously with bilateral sinus augmentation. Six implants (4 TM and 2 tapered) were placed and bone specimens obtained 6 months after grafting. Radiography and histologic analysis demonstrated that implants were positioned in non-native bone. Removal torque test, performed at second stage procedure, confirmed the successful osseointegration of implants. The definitive implant-supported full-arch prosthesis was then constucted and placed in function. Conclusion: The positive outcomes of this case report suggested that the rehabilitation of severely atrophic maxillary arch might be achieved by merging TM with new regenerative techniques without harvesting conspicuous quantities of autogenous graft.

2013 - Comparative in vitro study of four commercial biomaterials used for bone grafting. [Articolo su rivista]
Bosetti, M; Bianchi, Ae; Zaffe, Davide; Cannas, M.
abstract

Purpose: This work aimed to study and compare the behavior of macrophages and human osteoclast-like cells cultured in contact with four commercial bone substitute materials used as graft for ridge augmentation techniques. Two materials are of natural origin and two are synthetic bone substitutes. 
Methods: Macrophage activation and cytokine release were assessed using SEM analysis and a sandwich ELISA kit while the activity of human osteoclast-like cells was studied quantifying calcium released from the substrata studied together with SEM analysis of cell morphology and pit formation on the bone substitutes.
Results: Hydroxyapatite proved to be the greatest macrophage activator, while the bovine derived material turned out to be the only bone substitute that does not induce macrophages to release IFNg. No material had direct induction of osteoclast precursor differentiation even if mature osteoclasts showed the highest activity on the human derived material followed by bone ceramic, while the bovine derived material was the substrate with the least osteoclast activity. 
Conclusions: The four materials reacted differently with the cells tested and between them, the bovine derived bone, being the lowest macrophage and osteoclast activator may be considered a good bone substitute for clinical situations requiring greater time of permanence of the material at the site of implantation, while human derived bone will be more suitable for clinical applications that require lower time of permanence.

2013 - Full-Arch Vertical Reconstruction of an Extremely Atrophic Mandible With "Box Technique." A Novel Surgical Procedure: A Clinical and Histologic Case Report [Articolo su rivista]
A., Menoni; F., Bernardello; S., Spinato; Zaffe, Davide
abstract

Purpose: To describe a new augmentation procedure named "box technique" for bone reconstruction in a severely atrophic jaw with mandibular and mental nerve dehiscence. Material and Methods: The first surgical box technique procedure was performed to augment the atrophic posterior area. Simultaneously, 2 implants were inserted into the interforaminal zone to stabilize the denture. After 6 months, 2 implants were positioned in the regenerated bone, and a second box technique procedure was performed to reconstruct the ridge in the area of fixture exposition. Six months after the second surgery, the patient was rehabilitated with a removable prosthesis retained on 4 implants. Results: The clinical and histologic analyses highlighted outstanding healing resulting from this vertical and horizontal allografting and included complete resorption of poly D,L-lactide meshes and substitution of the mineralized human bone allograft with an excellent quality new bone formation. Conclusions: Results confirm the effectiveness of the technique, which needs a further case series study endorsing its reliability. (Implant Dent 2013;22:2-7)

2013 - Hydrogen sulfide slows down progression of experimental Alzheimer's disease by targeting multiple pathophysiological mechanisms. [Articolo su rivista]
Giuliani, Daniela; Ottani, Alessandra; Zaffe, Davide; Galantucci, M; Strinati, F; Lodi, Renzo; Guarini, Salvatore
abstract

It has been previously reported that brain hydrogen sulfide (H2S) synthesis is severely decreased in Alzheimer's disease (AD) patients, and plasma H2S levels are negatively correlated with the severity of AD. Here we extensively investigated whether treatment with a H2S donor and spa-waters rich in H2S induces neuroprotection and slows down progression of AD. Studies with sodium hydrosulfide (a H2S donor) and Tabiano's spa-water were carried out in three experimental models of AD. Short-term and long-term treatments with sodium hydrosulfide and/or Tabiano's spa-water significantly protected against impairment in learning and memory in rat models of AD induced by brain injection of β-amyloid1-40 (Aβ) or streptozotocin, and in an AD mouse model harboring human transgenes APPSwe, PS1M146V and tauP301L (3xTg-AD mice). The improvement in behavioral performance was associated with hippocampus was size of Aβ plaques and preservation of the morphological picture, as found in AD rats. Further, lowered concentration/phosphorylation levels of proteins thought to be the central events in AD pathophysiology, namely amyloid precursor protein, presenilin-1, Aβ1-42 and tau phosphorylated at Thr181, Ser396 and Ser202, were detected in 3xTg-AD mice treated with spa-water. The excitotoxicity-triggered oxidative and nitrosative stress was counteracted in 3xTg-AD mice, as indicated by the decreased levels of malondialdehyde and nitrites in the cerebral cortex. Hippocampus reduced activity of c-jun N-terminal kinases, extracellular signal-regulated kinases and p38, which have an established role not only in phosphorylation of tau protein but also in inflammation and apoptosis, was also found. Consistently, decrease in tumor necrosis factor-α level, up-regulation of Bcl-2, and down-regulation of BAX and the downstream executioner caspase-3, also occurred in the hippocampus of 3xTg-AD mice after treatment with Tabiano's spa-water, thus suggesting that it is also able to modulate inflammation and apoptosis. Our findings indicate that appropriate treatments with H2S donors and Tabiano's spa-waters, and may be other spa-waters rich in H2S content, might represent an innovative approach to slow down AD progression in humans by targeting multiple pathophysiological mechanisms.

2013 - Immunocytochemical and structural comparative study of committed versus multipotent stem cells cultured with different biomaterials. [Articolo su rivista]
Palumbo, Carla; Baldini, Andrea; Cavani, Francesco; Sena, Paola; Benincasa, Marta; Ferretti, Marzia; Zaffe, Davide
abstract

The aim of this work was the comparison of the behavior of committed (human osteoblast cells - hOB - from bone biopsies) versus multipotent (human dental pulp stem cells - hDPSC - from extracted teeth) cells, cultured on shot-peened titanium surfaces, since the kind of cell model considered has been shown to be relevant in techniques widely used in studies on composition/morphology of biomaterial surfaces. The titanium surface morphology, with different roughness, and the behavior of cells were analyzed by confocal microscope (CM), scanning electron microscope (SEM) and X-ray microanalysis. The best results, in terms of hOB adhesion/distribution, were highlighted by both CM and SEM in cultured plates having 20-mum-depth cavities. On the contrary, CM and SEM results highlighted the hDPSC growth regardless the different surface morphology, arranged in overlapped layers due to their high proliferation rate, showing their unfitness in biomaterial surface test. Nevertheless, hDPSC cultured inside 3D-matrices reproduced an osteocyte-like three-dimensional network, potentially useful in the repair of critical size bone defects. The behavior of the two cell models suggests a different use in biomaterial cell cultures: committed osteoblast cells could be appropriate in selecting the best surfaces to improve osseointegration, while multipotent cells could be suitable to obtain in vitro osteocyte-like network for regenerative medicine. The originality of the present work consists in studying for the first time two different cell models (committed versus multipotent) compared in parallel different biomaterial cultures, thus suggesting distinct targets for each cellular model. Copyright 2012 Elsevier Ltd. All rights reserved.

2013 - Modulation of the JAK/ERK/STAT signaling in melanocortin-induced inhibition of local and systemic responses to myocardial ischemia/reperfusion [Articolo su rivista]
Ottani, Alessandra; Maria, Galantucci; Ettore, Ardimento; Laura, Neri; Canalini, Fabrizio; Calevro, Anita; Zaffe, Davide; Ettore, Novellino; Paolo, Grieco; Giuliani, Daniela; Guarini, Salvatore
abstract

The janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) pathways have been shown to play a cardioprotective role. We previously gave evidence that melanocortins afford cardioprotection in conditions of myocardial ischemia/reperfusion. Here we aimed to investigate the influence of melanocortins on the JAK/ERK/STAT signaling in cardiac and systemic responses to prolonged myocardial ischemia/reperfusion. Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30 min. At the end of the 2-h reperfusion, western blot analysis of the cardioprotective transcription factors pJAK2, pERK1/2, pTyr-STAT3 and pSer-STAT3, the inflammatory mediator tumor necrosis factor-α (TNF-α), the pro-apoptotic factors BAX and c-jun N-terminal kinases (pJNK), the anti-apoptotic protein Bcl-XL, as well as of the cardioprotective enzyme heme oxygenase-1 (HO-1), was performed in the left ventricle and spleen. Intravenous treatment, during coronary artery occlusion, with the melanocortin analogs [Nle4, D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH) and adrenocorticotropic hormone 1-24 [ACTH-(1-24)], induced a left ventricle up-regulation of pJAK2, pERK1/2 and pTyr-STAT3 (JAK-dependent), and a reduction in pJNK and TNF-α levels; these effects of NDP-α-MSH and ACTH-(1-24) were associated with over-expression of the pro-survival proteins HO-1 and Bcl-XL, and marked decrease of the myocardial infarct size. Melanocortin treatment did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and BAX levels. In the spleen, NDP-α-MSH and ACTH-(1-24) induced similar effects on the expression of the above transcription factors/proteins, except for pERK1/2 (down-regulated) and HO-1 (unaffected). Blockade of JAK and ERK pathways with AG490 and U0126, respectively, abrogated the myocardial infarct size reduction by NDP-α-MSH. These results indicate that melanocortins inhibit local and systemic inflammatory and apoptotic cascades triggered by prolonged myocardial ischemia/reperfusion, with consequent reduction in myocardium infarct size, seemingly via activation of the JAK/STAT signaling and with modulation of an ERK (STAT unrelated) signaling pathway.

2013 - Non-bacterial protein expression in periodontal pockets by proteome analysis [Articolo su rivista]
Bertoldi, Carlo; Bellei, Elisa; Chiara, Pellacani; Davide, Ferrari; Andrea, Lucchi; Aurora, Cuoghi; Bergamini, Stefania; Pierpaolo, Cortellini; Tomasi, Aldo; Zaffe, Davide; Monari, Emanuela
abstract

Objectives: To compare the proteomic profile of inter-proximal pocket tissues with inter-proximal healthy tissues in the same subject to reveal proteins associated with periodontal disease in sites where periodontopathogenic bacteria were not detectable. Methods: Twenty-five healthy patients, with moderate-to-advanced chronic periodontitis and presenting with at least one intra-bony defect next to a healthy inter-proximal site were enrolled. The periodontal defects were treated with osseous resective surgery, and the flap design included both the periodontal pockets and the neighbouring inter-proximal healthy sites. Pocket-associated and healthy tissues were harvested for proteomic analyses. Results: Fifteen proteins were differently expressed between pathological and healthy tissues. In particular, annexin A2, actin cytoplasmic 1, carbonic anhydrase 1 & 2; Ig kappa chain C region (two spots) and flavinreductase were overexpressed, whereas 14-3-3 protein sigma and zeta/delta, heat-shock protein beta -1 (two spots), triosephosphateisomerase, peroxiredoxin-1, fatty acid-binding protein-epidermal, and galectin-7 were underexpressed in pathological tissue. Conclusions: The unbalanced functional network of proteins involved could hinder adequate tissue response to pathogenic noxa. The study of periodontal pocket tissue proteomic profile would be crucial to better understand the pathogenesis of and the therapeutic strategies for periodontitis.

2013 - Risk factors and socioeconomic condition effects on periodontal and dental health: A pilot study among adults over fifty years of age [Articolo su rivista]
Bertoldi, Carlo; Lalla, Michele; Pradelli, J. M.; Cortellini, P.; Lucchi, A.; Zaffe, Davide
abstract

Objective: Observational studies on the association among systemic / general and oral cavity indices, tooth loss, periodontal conditions, and socioeconomic inequalities are to be still performed in the population of Southern Europe. This study aims to determine the extent of this relationship among Italian healthy adults 50 years of age and above. Materials and Methods: Socioeconomic and lifestyle characteristics, cardiovascular indicators, and systemic indices were examined by contrasting the dental indices among adult people of Northern Italy. Data were processed through correlation analysis, and multivariate analysis was carried out using seemingly unrelated regressions. Results: A total of 118 adults 50 years of age and above were anamnesed and underwent systemic 50 years of age and above, after anamnesis, underwent systemic and dental examination. Their socioeconomic status was found to be inversely associated only with smoking and dental parameters. Unexpected outcomes between lifestyle and risk factors were detected. The statistical analysis showed an uneven correlation among dental indices and between those indices and the socioeconomic status, such as, a periodontal condition, apparently free from influences, unusually became worse as class was enhanced. became worse as the socioeconomic status enhanced.Conclusions: The study outcomes indicate a relationship between tooth loss and conservative endodontic therapy, but they result in alternative choices. Nevertheless, the socioeconomic status has an inverse relationship with tooth loss and conservative endodontic therapy, but a direct relation with worsening of the periodontal condition. This pilot study highlights a need for the public health administration to adopt a socioeconomic assessment not only based on the household income, but also to accordingly improve its therapeutic course.

2013 - Up-regulation of the canonical Wnt-3A and Sonic hedgehog signaling underlies melanocortin-induced neurogenesis after cerebral ischemia [Articolo su rivista]
Spaccapelo, Luca; Galantucci, Maria; Neri, Laura; Contri, Miranda; R., Pizzala; D'Amico, Roberto; Ottani, Alessandra; Sandrini, Maurizio; Zaffe, Davide; Giuliani, Daniela; Guarini, Salvatore
abstract

In experimental cerebral ischemia, melanocortin MC4 receptor agonists induce neuroprotection and neurogenesis with subsequent long-lasting functional recovery. Here we investigated the molecular mechanisms underlying melanocortin-induced neurogenesis. Gerbils were subjected to transient global cerebral ischemia, then they were treated every 12 h, and until sacrifice, with 5-bromo-2'-deoxyuridine (BrdU; to label proliferating cells), and the melanocortin analog [Nle(4),D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) or saline. NDP-alpha-MSH increased hippocampus dentate gyrus (DG) expression of Wnt-3A, beta-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin (DCX), as detected at days 3, 6 and 10 after the ischemic insult. Further, an elevated number of BrdU immunoreactive cells was found at days 3 and 10, and an improved histological picture with reduced neuronal loss at day 10, associated with learning and memory recovery. Pharmacological blockade of the Wnt-3A/beta-catenin and Shh pathways, as well as of melanocortin MC4 receptors, prevented all effects of NDP-alpha-MSH. These data indicate that, in experimental brain ischemia, treatment with melanocortins acting at MC4 receptors induces neural stem/progenitor cell proliferation in the DG by promptly and effectively triggering the canonical Wnt-3A/beta-catenin and Shh signaling pathways. Activation of these pathways is associated with up-regulation of the repair factor Zif268 and the neurogenesis facilitating factor IL-10, and it seems to address mainly toward a neuronal fate, as indicated by the increase in DCX positive cells.

2012 - Antonio Scarpa, anatomista e chirurgo tra mito e storia. [Articolo su rivista]
Lavini, C.; Lodi, Renzo; Zaffe, Davide
abstract

L'articolo si occupa della storia della vita privata, di docente e di ricercatore, di Antonio Scarpa, Anatomico e Chirurgo.

2012 - In Vivo Comparison of Two Bone Substitutes in the Distal Femur of the Rabbit [Articolo su rivista]
Bertoldi, Carlo; Zaffe, Davide
abstract

Purpose: This study aimed to micro radiographically evaluate the healing of grafted defects using a surgically standardized model that was suitable for comparing the regenerative potential of different grafts. Materials and Methods: Two different biomaterials, bovine porous bone mineral (BPBM) and nanohydroxyapatite (NHA), were used to fill defects produced in the distal epiphyses of 10 adult male rabbits for 2 and 4 months. Three rabbits were left untreated, without defects, as controls. Evaluations were performed on microradiographs of sections of polymethyl methacrylate-embedded rabbit epiphyses. The amounts of graft material and bone were evaluated by splitting the filled hole into three portions. Results: A greater amount of BPBM granules were in contact with bone at both 2 and 4 months versus the NHA (statistically significant difference in the central portion of the defect), and a persistence of the BPBM over time was apparent. The amount of NBA decreased from the inner to the outer portion of the defect, particularly after 4 months. The bone amount increased from the inner to the outer portion, particularly for the NHA graft, which produced an early cortex. The amount of mineralized material reached about 80% in the BPBM and 40% to 60% in the NBA after 4 months. Conclusion: Both the analyzed biomaterials performed adequately for bone regeneration. The two biomaterials are probably suitable for grafting defects related to early cortical formation or spacemaintaining clinical requirements. PMID: 22299088 IDS Number: 893WZ

2011 - Atrophic maxillary floor augmentation by mineralized human bone allograft in sinuses of different size: an histologic and histomorphometric analysis. [Articolo su rivista]
C. M., Soardi; S., Spinato; Zaffe, Davide; H. L., Wang
abstract

AbstractObjective: The aims of this work were to histologically examine the healing of mineralized human bone allograft (MHBA) in sinus augmentation for elevating a severe maxillary atrophy ridge (2mm residual ridge height) and to correlate the results to the sinus cavity size.Material and methods: A two-stage protocol was conducted in 23 patients, all having crestal bone 2mm. A mixture of 80/20 cortical/cancellous of MHBA particles was used to augment sinus using the lateral window approach in narrow (NS; o15mm bucco-palatal distance) and wide (WS; 15mm bucco-palatal distance) sinuses, based upon computerized tomography (CT) assessment. A bone core biopsy was taken at implant placement, 6 and 9 months after surgery. Microradiography, histology and histochemistry of methacrylate-embedded sections were performed to analyze and to evaluate the bone and graft amount.Results: Newly formed bone around MBHA particles was found in all 28 biopsies. Bone showed a woven structure at 6 months after surgery and a lamellar structure 9 months after surgery. At 6 months after surgery, the 13 NS and 15 WS had 30.5 8.8% and 20.7 4.9% mean SD bone formation, respectively. At 9 months after surgery, it was 38.8 7% (NS) and 30.7 3% (WS). Residual graft was about 16% (6 months) and 6% (9 months), in both NS and WS. The Mann–Whitney test showed agreater bone formation in NS than in WS (Po0.005).Conclusions: The used 80/20 MHBA mixture appears to promote, in the severe atrophic maxilla, a satisfactory bone formation. Our results prove that the larger the sinus, the longer the maturationtime needed to achieve a suitable amount of new bone formation.

2011 - Behavior of aqueous-nanocrystalline-hydroxyapatite in oral bone regeneration [Articolo su rivista]
Zaffe, Davide; G., Traversa; M., Mozzati; F., Morelli; G., D’Angeli
abstract

ABSTRACTPurpose: A skeletal segment consisting exclusively of bone is the target outcome of bone regeneration. Granular hydroxyapatitesform a hydroxyapatite-bone composite, unsuitable for effectively supporting implants, which may persist for manyyears. This work aimed to investigate the reasons for the bone replacement of Ostim®, a recently commercialized aqueousnanocrystalline hydroxyapatite.Methods: Histology, SEM and X-ray microanalysis were employed to analyze 6- to 9-month biopsies of post-extractive sitesor sinus floor lifts of the maxilla in 15 subjects.Results: The results highlight a great bone formation, Ostim® resorption with time by osteoclasts but also interstitial fluid propagationof Ostim® masses by percolation. A possible osteocyte protoplasmic involvement was also at work in concert to reach the target.Conclusions: The use of Ostim® as bone regenerating material leads to the formation of a highly suitable implant supportconsisting exclusively of bone in less than 12 months, i.e. in a remarkably short time.

2011 - Diode Laser irradiation and fluoride uptake in human teeth [Articolo su rivista]
M. C., Vitale; Zaffe, Davide; A. R., Botticelli; C., Caprioglio
abstract

AIM: To evaluate chemically the effects of diode laser onfluoride uptake before and after laser irradiation of enamelsurfaces. METHODS: Crowns of 20 sound human teethwere halved and a 3x3mm acid-resistant varnish uncoveredwindow left for: A) no treatment; B) fluoride (Elmexgel); C) diode (fluoride + diode laser); D) diode (diodelaser + fluoride). The dental surfaces were analysed usinga fluoride ion-selective electrode, in order to evaluatethe fluoride treatment in combination with a diode laser.Also, to investigate laser-induced compositional changes(contents in F-) in enamel before/after laser irradiation andtopical fluoride application. RESULTS: The mean ±SD offluoride uptake of teeth of group A was 1.55 ± 0.89 mg/l.Mean fluoride uptake increased sevenfold after fluoridegel treatment: 10.51 ± 3.38 mg/l for group B, up to 15times after gel and laser treatment: 23.62 ± 3.58 mg/lfor group C and was 22.7 ± 4.60 mg/l for group D (diodelaser before fluoride application). The Kruskal Wallis testindicated a statistically significant effect of fluoride uptakefor all three treatments (p<0.001). The Student-Newman-Keuls multiple comparison test indicated a statisticallysignificant increase of fluoride uptake before and after alltreatments, and also a statistically significant difference forlaser treatment versus fluoride gel. However, there was nostatistically significance difference between laser groups.CONCLUSIONS: There is an enhanced capability oflasers to increase fluoride uptake of enamel and providingprotection to enamel surface from acid attack.

2011 - Melanocortin MC(4) receptor agonists counteract late inflammatory and apoptotic responses and improve neuronal functionality after cerebral ischemia. [Articolo su rivista]
Spaccapelo, L; Bitto, A; Galantucci, M; Ottani, Alessandra; Irrera, N; Minutoli, L; Altavilla, D; Novellino, E; Grieco, P; Zaffe, Davide; Squadrito, F; Giuliani, Daniela; Guarini, Salvatore
abstract

Indirect evidence indicates that, in cerebral ischemia, melanocortins have neuroprotective effects likely mediated by MC(4) receptors. To gain direct insight into the role of melanocortin MC(4) receptors in ischemic stroke, we investigated the effects of a highly selective MC(4) receptor agonist. Gerbils were subjected to transient global cerebral ischemia by occluding both common carotid arteries for 10min. In saline-treated stroke animals, an impairment in learning and memory occurred that, at day 11 after stroke, was associated with hippocampus up-regulation of tumor necrosis factor-α (TNF-α), BAX, activated extracellular signal-regulated kinases (ERK1/2), c-jun N-terminal kinases (JNK1/2) and caspase-3, down-regulation of Bcl-2, and neuronal loss. Treatment for 11days with the selective melanocortin MC(4) receptor agonist RO27-3225, as well as with the well known non-selective [Nle(4),D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) as a reference non-selective melanocortin, counteracted the inflammatory and apoptotic responses, as indicated by the changes in TNF-α, BAX, ERK1/2, JNK1/2, caspase-3 and Bcl-2 protein expression. Furthermore, melanocortin treatment reduced neuronal loss and dose-dependently improved learning and memory. These positive effects were associated with overexpression of Zif268, an immediate early gene involved in injury repair, synaptic plasticity and memory formation. Pharmacological blockade of MC(4) receptors with the selective MC(4) receptor antagonist HS024 prevented all effects of RO27-3225 and NDP-α-MSH. These data give direct evidence that stimulation of MC(4) receptors affords neuroprotection and promotes functional recovery from stroke, by counteracting prolonged and/or recurrent inflammatory and apoptotic responses, and likely by triggering brain repair pathways.

2011 - Treatment of cerebral ischemia with melanocortins acting at MC(4) receptors induces marked neurogenesis and long-lasting functional recovery. [Articolo su rivista]
Giuliani, Daniela; Zaffe, Davide; Ottani, Alessandra; Spaccapelo, L; Galantucci, M; Minutoli, L; Bitto, A; Irrera, N; Contri, Miranda; Altavilla, D; Botticelli, Ar; Squadrito, F; Guarini, Salvatore
abstract

Melanocortins produce neuroprotection against ischemic stroke with subsequent long-lasting functional recovery, through melanocortin MC(4) receptor activation. Here we investigated whether the long-lasting beneficial effect of melanocortins in stroke conditions is associated with a stimulation of neurogenesis. Gerbils were subjected to transient global cerebral ischemia by occluding both common carotid arteries for 10 min; then, they were prepared for 5-bromo-2'-deoxyuridine (BrdU) labeling of proliferating cells. Delayed treatment (up to 9 h after the ischemic injury) for 11 days with the melanocortin analog [Nle(4),D: -Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) improved learning and memory throughout the 50-day observation period. Immunohistochemical examination of the hippocampus on day 50 showed, in the dentate gyrus, an elevated number of BrdU immunoreactive cells colocalized with NeuN (used as indicator of mature neurons) and Zif268 (used as indicator of functionally integrated neurons). Retrospective analysis during the early stage of neural stem/progenitor cell development (days 3 and 4 after stroke) showed, in NDP-α-MSH-treated gerbils, a high degree of daily cell proliferation and revealed that NDP-α-MSH favorably affects Wnt-3A signaling pathways and doublecortin expression. Pharmacologic blockade of MC(4) receptors prevented all effects of NDP-α-MSH. These data indicate that treatment of cerebral ischemia with MC(4) receptor agonists induces, with a broad window of therapeutic opportunity, long-lasting functional recovery associated with a large number of mature and likely functional newborn neurons in brain injured areas. Our findings reveal previously undescribed effects of melanocortins which might have major clinical implications

2011 - Valutazione al SEM dell’assorbimento di fluoro nei tessuti duri dentari in seguito ad irraggiamento con laser ad Erbio e a Diodi. [Articolo su rivista]
G., Macconi; M., Maggioni; A., Botticelli; Zaffe, Davide; A., Profumo; M. C., Vitale; L., Damia
abstract

Gli incoraggianti risultati ottenuti nel presente lavoro portano a indicare come il trattamento dell’ipersensibilità dentinale con gel al fluoro e sorgenti laser, utilizzate secondo i protocolli indicati, rappresenti oggi il miglior standard clinico disponibile per taleindicazione. L’interpretazione dei risultati ottenuti porta ad ipotizzare il trattamento con gel di fluoro e laser a Diodi comedi elezione per il trattamento dell’ipersensibilità dentinaleai colletti per il maggior assorbimento di fluoro ottenuto. Iltrattamento con gel di fluoro e laser ad Erbio comunque nonè trascurabile, e lascia spazio per ulteriori analisi a diversiparametri d’applicazione.

2010 - Bone defects healing by hyaluronic acid: preliminary results. [Articolo su rivista]
A., Baldini; Zaffe, Davide; G., Nicolini
abstract

Aim. The aim of this study is to evaluate the capability ofHyaloss™ matrix (Fab – Fidia Advanced Biopolymers –Pd – Italy), a biomaterial based on hyaluronic acid, usedas organic scaffold in bone repair in post-extractive defects.Materials and methods: 20 post-extractive sockets wereselected, with similar size defects in the same patientand in the same hemiarch. Hyaluronic acid with high molecularweight (Hyaloss™ matrix, Fab – Pd – Italy) wasmixed with autologous bone obtained using Safescraper® curve (Meta – Re – Italy) to repair post-extractivesites. Safescraper® is a cutting edge system thatallows to the collection of autologous bone withoutusing traditional, incision-based collection techniques,which could cause discomfort to the patient.Results: Clinical and hystological evaluations were performed,four months after grafting, in the maxilla and inthe mandible. From a clinical point of view Hyaloss™matrix mixed with autologous bone and patient’s bloodbecomes a substance similar to gel, which is easy to insertin to the defect. From a hystological point of view, inthe treated site there is the presence of an erosive activity,with accelerated angiogenetic and bone remodellingactivities.Conclusions: The preliminary results show an accelerationof the bone deposit process and of its remodellingdue to the presence of Hyaloss™ matrix, which, from a clinical point of view, improves the handling and applicationof the bone matrix inside the defects and, from ahystologic point of view makes it possible to obtainbone regeneration in less time when it is used with autologousbone.

2010 - Carious dentin treatment for glass ionomer cement adhesion: a comparative study. (2010) 1(10):WMC001091..Autore/i. [Working paper]
Zaffe, Davide; A. R., Botticelli; M., Bellincampi; M., Chiesa; M., Vitale
abstract

Abstract - Carisolv method is a minimally invasive treatment of carious lesions which may improve patient collaboration and allow care of minimal dental cavities, especially in young people. The aim of this study was to compare H3PO4 and Carisolv in vitro treatments of human dentin applying microradiography, SEM examination and X-ray microanalysis to evaluate the capacity of these products to clean dentin surface for glass ionomer cement (GCI) application. Forty extracted permanent molars with dentin caries were treated with 35% H3PO4 or Carisolv gel according to manufacturer instructions. Ten teeth of each group were filled with GCI and then embedded in methyl-methacrylate (PMMA). The PMMA blocks were sectioned, polished and microradiographed. The remaining teeth were dehydrated and desiccated in a critical point dryer. Sections and teeth were then prepared for SEM and X-ray microanalysis. H3PO4 treatment produced unpolished surfaces (probably due to mineral re-precipitation), demineralization of dentin, exorbitant tubule widening, highly irregular dentin surface of cavities, and dentin fragments embedded by GCI. Carisolv treatment produced polished dentin surfaces with open tubules, little crystal re-precipitation, good GCI adhesion and penetration inside tubules. The chemo-mechanical method (Carisolv) seems to be a good technique for treating carious cavities, minimizing dentin injury and providing an appropriate surface for adhesive bonding.

2010 - Cytopathological and chemico-physical analyses of smears of mucosa surrounding oral piercing [Articolo su rivista]
S. M., Lupi; Zaffe, Davide; R. R. Y., Baena; S., Rizzo; A. R., Botticelli
abstract

Objective: The aim of this comparative study was to analyze cytopathologically and chemico-physically the mucosa surrounding oral piercing to correlate results with adverse tissue signs. Materials and methods: The tongue superficial mucosa of 15 young subjects (control group) and the superficial mucosa surrounding oral piercing of 15 young subjects (test group, TG) were smeared on slides, Papanicolaou stained and analyzed under the optical microscope. Some smears were prepared for (back-scattered) scanning electron microscope (SEM) and X-ray microanalysis to study piercing fragments. Results: Smears of TG displayed a variable extent of bacterial cytolysis of epithelial cells, fungi, hyperkeratosis, parakeratosis, granulocyte infiltration, calcium formations and bacterial flora; the four last statistically significant (P < 0.05). Foreign bodies surrounded by keratinocytes were detected under both light and SEM. X-ray microanalyses highlighted piercing alloy aggression, ion release and an inverse gradient of ion concentration inside keratinocytes. Conclusions: The pathological findings in smears correlated with adverse effects of oral piercing. Ion release may be related to direct toxic effects and belated reactions because of metal sensitization. A strict regulation of piercing is warranted.

2010 - L'alba della vita e la via dell'ossigeno [Articolo su rivista]
Lodi, Renzo; Zaffe, Davide
abstract

Gli Autori affrontano l'argomento partendo dalla comparsa dell’ossigeno sulla terra e facendoci comprendere quale siano il ruolo e le prospettive del suo impiego in medicina.

2010 - Liver injury by experimental portal bacteremia: histogenetic recovery study in the rat [Working paper]
Manenti, A.; Trenti, L.; Reggiani Bonetti, L.; Zaffe, Davide; Botticelli, A.
abstract

Abstract - To study the histogenetic recovery of hepatic lesions due to portal bacteremia, a complication of some clinical conditions, an experimental animal model had developed. Portal bacteremia was performed in 8-week rats and the morphological recovery of liver was histologically checked 1 to 6 days after bacteria inoculation. The major injuries, such as acute inflammatory exudate of the portobiliary spaces, piecemeal necrosis of muralium, micro-abscesses and areas of hepatocyte necrosis of the liver parenchyma, and thrombosis in the centrolobular vein were recorded 1 day after inoculation. Minimal signs of vacuolar degeneration, steatosis, necrosis areas, vessel congestion and focal hemosiderosis together with a small hepatocyte proliferative activity was instead appreciable with longer time. The results seem to suggest a role of vascular structures and Kupffer cells in the morphological repair. This experimental model could serve to understand better similar clinical hepatology conditions, such as portal bacteremia.Informazioni utili

2010 - Microscopy of laser effects on hard and soft oral tissues [Capitolo/Saggio]
Zaffe, Davide; A. R., Botticelli; M. C., Vitale; C., Piacentini
abstract

Lasers are instruments generating high-powerelectromagnetic radiation more often used in biomedicine.This beam, which physical characteristic andpower depend on the generating device and powersupply circuit, may be usefully employed in surgicalfield to easy cut, excise or eliminate soft tissues ortheir portions, and in the treatment of hard tissues,in particular in some therapies of calcified tissues ofteeth. Aim of this chapter is to show the morphological,histochemical, immunocytologic and chemicalphysicaleffects of hard and soft tissues of the oralcavity treated with laser or others instrumentation.

2010 - Preservazione con collagene riassorbibile del sito postestrattivo prima del posizionamento di impianti a carico immediato in zone estetiche* Presentazione di un caso e valutazione istologica a 4 mesi [Articolo su rivista]
R., Borgia; V., Farina; F., Franceschini; R., Monguzzi; Zaffe, Davide
abstract

The membranes of barrier made by resorbable collagen proved suitable procedures for use in guided tissue regeneration (GTR) and like correction of anatomical defects.This article calls for the use of absorbable collagen plugs for use in extraction sockets to maintain the volumes of the bone ridge and allow the placement of implants in the frontal areas with better appearance. We explain how to use this material. To this end we presente the characteristics of the material and argue indications and contraindications. We show a case of practical application of these principles and the details of this technique. The objective of this study is to present a technique, that, used in appropriate cases, is easily applicable and allows to obtain better aesthetic result in the rehabilitation of immediate loading at the stage of provisional prosthesis.

2010 - Rialzo del pavimento sinusale in mascellari estremamente atrofici:valutazione della neoformazione ossea con innesti di osso omologo mineralizzato [Articolo su rivista]
C. M., Soardi; A. E., Bianchi; S., Spinato; Zaffe, Davide
abstract

This paper examines the healing, by means of mineralized human bone allograft in sinus lift procedures, of severe maxillary atrophy, also in relation to the sinu-sal cavity size.In a two stage protocol, 14 core biopsies have been taken by a trephine bur to place the implants in 12 patients, all having the crestal bone lesser than or equal to 2 mm. Sinus augmentation by lateral window was performed six months earlier using a mixture of cortical/cancellous MHBA particles (80%/2O%) (Puros®). Microradiography, histology and histochemistry of methacrylate-embedded sections were performed to evaluate the amount of bone and graft. Newly formed bone around MBHA particles was found in all 14 biopsies. Bone chiefly showed a woven structure; sometimes however a lamellar structure was reported on the periosteal side. Six months later, the mean bone amount in narrow sinuses was 25.6% and the graft about 15.8%.Based on the preoperative computer tomography sections (< or > 15 mm) the sinusal cavities were classified as Narrow Sinus (NS) and Broad Sinus (BS). The mean bone amount was 30.6% (NS) and 2O.6% (BS). The greater bone amount of NS was statistically significant (P<O.OO5) after Mann-Whitney test. To conclude, the use of the MHBA mixture (80%/ 20%) appears to promote adequate bone formation in severely atrophic maxillas.Our preliminary results, prove that the larger the sinus, the longer the maturation time required to achieve a suitable amount of new bone formation.

2010 - STATIC OSTEOGENESIS AND DYNAMIC OSTEOGENESIS: THEIR RELEVANCE IN DENTAL BONE IMPLANTS AND BIOMATERIAL OSSEOINTEGRATION [Articolo su rivista]
Marotti, Gastone; Zaffe, Davide; Ferretti, Marzia; Palumbo, Carla
abstract

The present report summarizes the results of a series of investigations carried out in our laboratory on intramembranous ossification occurring under normal condition during skeletal organogenesis and osseointegrations of dental implants and biomaterials. No morphological differences were observed between normal and pathological conditions, since the same following sequence of events were found. Inside the embryonic mesenchyme or the connective tissue formed after bleeding, due to surgery, cords of plum cells, displaying the typical osteoblastic structure, differentiate in between the blood capillaries. These osteoblasts appear to be stationary since they do not move, but transform into osteocytes in the same site where they differentiated, thus giving origin to a trabecular woven-bone framework laid down by static osteogenesis (SO). Soon after, typical movable osteoblastic laminae differentiate along the surface of this SO-trabeculae and thicken them with lamellar bone formed by dynamic osteogenesis (DO). SO seems to depend on inductive stimuli and appears to be mechanically independent, whereas DO mainly depend on mechanical strains. Additionally SO-bone is a bad quality bone because of its woven texture and high microporosity, due to the many osteocyte lacunae it contains, whereas DO-bone generally is a lamellar bone and thus mechanically much more resistant.The clinical implication of these findings, as regards the time of load application after prostheses/biomaterials implantation, is discussed.

2010 - Vertical ridge augmentation tramite alloinnesto mineralizzato: comparazione clinica, istologica di 2 tecniche rigenerative in due diversi casi clinici [Articolo su rivista]
A. E., Bianchi; S., Spinato; C. M., Soardi; G., Greco; Zaffe, Davide
abstract

Various regenerative techniques were proposed for the treatment of wide vertical bone defects. In this research two clinical reports of very atrophic maxillary alveolar ridge were reported: one was treated with homologous bone block graft, while the second received a titanium mesh and homologous bone particulate. Clinical, histological and histomorphometric outcomes were compared.

2009 - Analisi di rilevanza del riscontro intralesionale degli Herpes simplex virus nei risultati della terapia parodontale rigenerativa [Articolo su rivista]
Bertoldi, Carlo; Pellacani, C.; Pinti, Marcello; Lalla, Michele; Lucchi, A.; Zaffe, Davide; Consolo, Ugo; Cossarizza, Andrea
abstract

Lo scopo del presente studio è quello di indagare la presenza degli herpes simplex virus 1 & 2 (HSVs) nelle lesioni angolari parodontali ed analizzarne l’influenza nella finalizzazione in terapia chirurgica rigenerativa parodontale. Materiali e Metodi: Sono stati complessivamente valutati 7 pazienti di cui 5 di sesso femminile e 2 di sesso maschile, di età compresa tra i 22 e i 60 anni sistemicamente sani. Dopo decontaminazione causale e di eventuali altri siti patologici, venivano eseguite indagini microbiologiche in ogni paziente con tamponi per escludere uno specifico ruolo batterico o micologico nell’ambito dei casi trattati. Immediatamente prima dell’intervento, un test biomolecolare (Meridol® Perio Diagnostics), basato sulla tecnologia realt-time polymerase chain reaction (RT-PCR), è stato utilizzato in rapporto al difetto angolare su cui intervenire ed ai solchi circostanti per escludere la presenza di batteri sicuramente parodontopatogeni (la cui presenza avrebbe portato all’esclusione del paziente dallo studio; ad egli, comunque, sarebbe stata garantita l’assistenza necessaria al caso). Il sito veniva trattato mediante minimally invasive surgical technique (MIST) e con enamel matrix protein (EMP – Emdogain , Biora AB, Malmö, Sweden). Il connettivo infiammatorio patologico presente nel difetto angolare veniva asportato, veniva inserito in provetta sterile e refrigerato immediatamente a -20 C°. Tale prelievo, in seguito, veniva preparato per la fase biomolecolare di rilevazione virale mediante sonde per acidi nucleici e real-time polymerase chain reaction (RT-PCR). Durante tutto il periodo di follow-up quindi il paziente veniva mantenuto in terapia di mantenimento e tutte le diverse misurazioni (FMPS, FMBS, PPD, REC, CAL) erano compiute in singolo-cieco da uno stesso operatore. In particolare le misurazioni erano effettuate prima dell’intervento (fase T0), a 6 mesi dall’intervento (T1) ed a una anno (T2); il follow-up era quindi a 12 mesi. Pur essendo registrati i diversi indici parodontali necessari alla terapia, la PPD rappresentava la variabile finale principale misurabile. L’analisi biomolecolare era condotta mediante estrazione del DNA virale e tecnica RT-PCR, come precedentemente descritto (7). Risultati I valori di PPD raccolti a T1 indicavano un miglioramento (non statisticamente significativo) degli stessi difetti per 11 delle tasche parodontali prese in esame, con una riduzione della profondità media di 1,5 mm, mentre in 3 casi non si registrava alcun sensibile miglioramento. I dati raccolti a T2 (fine del periodo di follow-up) mostravano una riduzione statisticamente significativa della PPD di tutti i difetti parodontali analizzati in rapporto a T0 ed, in particolare, il miglioramento medio era di 5,5 mm in termini di PPD. In 3 difetti angolari, tuttavia, tale miglioramento era stato piuttosto scarso e la profondità di tali difetti, anche in seguito al trattamento chirurgico, risultava ancora non fisiologica, ovvero persisteva una tasca. Le indagini biomolecolari hanno evidenziato che 6 dei siti tra i difetti parodontali valutati, erano positivi all’infezione da HSVs (si può considerare l’infezione da HSVs significativa con valori ≥ di 10 copie di DNA appartenente a tale agente su 1000 cellule analizzate). Il confronto tra la presenza e la concentrazione di HSVs con la profondità del difetto parodontale misurato in T2 ha indicato che i casi con un più alta concentrazione di copie virali coincidevano con i difetti parodontali che non avevano presentato un miglioramento significativo dopo il trattamento chirurgico dello stesso. In fase T0 non si erano riscontrate differenze statisticamente significative in termini di PPD tra i siti infettati da HSVs ed i restanti. Si può osservare anche una associazione lineare positiva e significativa tra PPD in T1 e PPD in T0. Mediante l’analisi dei coefficienti di correlazione anche in scala logaritmica si è p

2009 - Biomateriali come condizionanti la guarigione ossea nella profilassi strutturale [Capitolo/Saggio]
M., Mozzati; R., Pol; V., Arata; Zaffe, Davide
abstract

Capitolo sulle caratteristiche dei biomateriali e sul loro utilizzo.

2009 - Chemical durability and microstructural analysis of glasses soaked in water and in biological fluids [Articolo su rivista]
Cannillo, Valeria; F., Pierli; Ronchetti, Ivonne; Siligardi, Cristina; Zaffe, Davide
abstract

A new glass, obtained from Bioglass BG45S5 original composition by substituting CaO with MgO, was produced and its chemical durability and microstructural characteristics were compared with that of Bioglass1. The two glasses (labelled as BG45 and MG45) were soaked up to 4 weeks at physiological temperature in different solutions, i.e. bi-distilled water, Hank’s Buffered Salt Solution 61200 (labelled as HBSS+), Hank’s Buffered Salt Solution 14170 (labelled as HBSS ), and Kokubo’s SBF. Moreover, the influence of either flat or flake surfaces was analysed for both glasses. Results showed that the chemical durability of a glass in saline at 37 8C, evaluated through pH and ICP-AES chemical analysis of the leached components, depended mainly on the chemical composition of the soaking solution. Moreover, the MG45 glass never exhibited hydroxyapatite crystal formation on its surface also after soaking in calcium- containing solutions. The apatite crystallisation and deposition mechanism, typical of a bioactive glass, was induced only if the glass itself contained calcium. The contemporaneous presence of calcium in the glass and in the soaking solution improved the reactivity of the glass, as apatite crystals nucleated in a shorter time and grew more quickly. As regards the morphology of the glass surface, rougher surfaces favoured the formation of hydroxyapatite crystals on glasses containing calcium

2009 - Comparative study on bone regeneration of cystic lesions [Articolo su rivista]
Bertoldi, C.; Zaffe, D.; Lucchi, A.; Consolo, U.
abstract

Obiettivi. Determinare la rigenerazione ossea di difetti cistici delle ossa mascellari dopo riempimento con osso autologo o con copolimero PLA-PGA (Fisiograft ®) tramite valutazioni cliniche, radiologiche e istologiche. Materiali e Metodi. Otto pazienti maschi consenzienti, affetti da cisti odontogena in rapporto a elementi dentari a prognosi infausta in cui il trattamento endodontico clinico era fallito, sono stati sottoposti a intervento di enucleazione cistica e a innesto con osso autologo (gruppo di controllo GC) o con copolimero (gruppo di trattamento GT) con follow-up di 4 mesi. Risultati. I risultati clinici e radiologici (area, diametri, livelli di grigio) evidenziano un lieve miglior esito per il gruppo di controllo, senza differenze statistiche significative. L’analisi istologica delle biopsie di quattro mesi evidenziava uno steady-state osteogenico nel GC, con frammenti di osso risparmiato dagli osteoclasti e porzioni di osso neoformato. Osso neoformato a fibre intrecciate e attività fosfatasi alcalina positiva erano invece caratteristiche distintive del GT. L’ammontare di osso presente (TBV) non risultava differente nei due gruppi (m ~ 16,5%). Conclusioni. I risultati ottenibili con il copolimero, non molto diversi da quelli conseguiti con osso autologo, sono da considerarsi molto apprezzabili in considerazione della maneggevolezza del materiale e dell’assenza della necessità di un sito donatore secondario. Abstract Comparative study on bone regeneration of cystic lesions Objectives. To evaluate healing of cystic lesions in human jawbone filled with autologous bone or PLA-PGA copolymer (Fisiograft®), by means of clinical, radiological and histological methods. Material and Methods. After informed consent eight male patients underwent surgical treatment of dental cysts caused by teeth where endodontic treatment failed. Patients were randomly divided into 2 groups: the first (control group) received an autologous bone graft while the second (treatment group) was treated by copolymer with a follow-up of 4 months. Results. Autologous bone provided a lightly better clinical and radiological (area, diameters, gray level) outcome without statistically significant differences. Bone activities were enhanced in sites treated with copolymer, whereas a steady-state was observed with autologous bone. The amount of bone (TBV) was similar in both groups (m ~ 16,5%). Conclusions. Our results indicate that best outcomes are achieved using autologous bone graft, but good results can also follow the use of copolymer to promote healing of severe bone defects. Additionally, copolymer is easy to handle and does not require a secondary donor site.

2009 - Comparazione tra idrossiapatiti di derivazione sintetica e bovina su un modello animale. [Abstract in Atti di Convegno]
Bertoldi, Carlo; Veneziani, A.; Zaffe, Davide; Giannetti, Luca; Consolo, Ugo
abstract

Vedi allegato

2009 - Functional recovery after delayed treatment of ischemic stroke with melanocortins is associated with overexpression of the activity-dependent gene Zif268 [Articolo su rivista]
Giuliani, Daniela; Ottani, Alessandra; Letteria, Minutoli; Vincenzo Di, Stefano; Maria, Galantucci; Alessandra, Bitto; Zaffe, Davide; Domenica, Altavilla; Annibale R., Botticelli; Francesco, Squadrito; Guarini, Salvatore
abstract

Melanocortin peptides afford strong neuroprotection and improve functional recovery in experimental ischemic stroke; they also have established neurotrophic actions. The expression of the immediate early gene Zif268 is dependent on synaptic activity and is involved in injury repair and memory formation. Here, we investigated the role of Zif268 in learning and memory recovery after delayed treatment of ischemic stroke with the melanocortin analog [Nle4, d-Phe7]α-MSH (NDP-α-MSH). A 10-min period of global cerebral ischemia was induced by occluding both common carotid arteries in gerbils. Treatment with a nanomolar dose of NDP-α-MSH (every 12 h for 11 days) was performed starting 3 h or 9 h after stroke induction; where indicated, gerbils were pretreated with the melanocortin MC4 receptor antagonist HS024. Animals were subjected to the Morris water-maze test (four sessions from 4 to 50 days after the ischemic episode). Fifty days after stroke, histological damage and Zif268 expression were investigated in the hippocampus. Treatment with NDP-α-MSH significantly reduced hippocampal damage, including neuronal death, and improved learning and memory recovery. This protective effect was long-lasting (50 days, at least) and associated with Zif268 overexpression, with both schedules of NDP-α-MSH treatment. Pharmacological blockade of MC4 receptors prevented these effects. Our data indicate that MC4 receptor-mediated actions of melanocortins could trigger repair mechanisms able to improve neuronal functionality and synaptic plasticity, and to promote long-lasting functional recovery from ischemic stroke with Zif268 gene involvement.

2009 - Idrossiapatite sintetica e di origine bovina: impianto comparativo nel femore di coniglio [Articolo su rivista]
Bertoldi, Carlo; A., Veneziani; Consolo, Ugo; Zaffe, Davide
abstract

Scopo di questo studio preliminare è l’analisi istologica comparativa del comportamento di idrossiapatite bovina (IA-B) e idrossiapatite sintetica nanocristallina (IA-S) dopo riempimento di difetti ossei critici prodotti sperimentalmente in entrambi i femori del coniglio. Lo studio verrà condotto sui segmenti scheletrici inclusi in metacrilato senza alcuna decalcificazione e la valutazione effettuata su microradiografie e preparazioni convenzionali di sezioni dei campioni inclusi. Materiali e Metodi: In 5 conigli New Zealand (maschi del peso di 3,5 kg circa), un foro di Ø di 3 mm e di 8 mm di è stato prodotto nel condilo mediale, in direzione medio-laterale, tramite trephine sotto getto di fisiologica. In ciascun coniglio, il foro prodotto nei due femori era riempito in modo randomizzato con IA-B o con IA-S. I conigli sono stati sacrificati dopo 2 mesi e i campioni prelevati analizzati istologicamente mediante sezioni spesse (microradiografie) e sottili. sono state analizzate su microradiografie o istologicamente con colorazione di Blu di toluidina, Gomori , Congo rosso/Solocromo cianina. Risultati: Nessun coniglio innestato ha manifestato problemi clinici e si sono mantenuti in buona salute fino al sacrificio. Le radiografie dei segmenti scheletrici recisi, contenenti il biomateriale innestato, permettevano di discriminare solamente il lato contenente l’IA-B Nelle sezioni l’IA-B riempiva ancora completamente la cavità prodotta chirurgicamente Il foro era richiuso dall’accrescimento di un esile corticale che, in genere, non incorporava granuli. I granuli erano circondati da tessuto osseo neoformato dopo rimozione del tessuto preesistente lesionato dalla trephine. L’analisi istomorfometrica evidenziava la presenza di IA-B 59,4%, osso neoformato 6,8 %, tessuto molle 33,8%. Le sezioni di femori contenenti l’innesto di IA-S il foro era chiuso da una esile corticale e da uno strato di osso trabecolare neoformato L’IA-S riempiva gran parte del foro prodotto chirurgicamente ma mostrava gradi di degradazione variabili. Osso neoformato era comunque in contatto con tutta la superficie dell’innesto che, frequentemente, in questa sede mostrava il grado di radiopacità originale. L’analisi istomorfometrica indicava la presenza di IA-S 78.5%, osso neoformato 8,5%, tessuto molle 13,0%. Conclusioni: i risultati preliminari di questo studio pilota indicherebbero una sostanziale identità di comportamento delle due idrossiapatiti nel brevissimo termine. La prosecuzione con tempi più lunghi potrà in seguito indicare quale dei due materiali sarà in grado di promuovere la maggior crescita ossea.

2009 - In vitro and in vivo behaviour of zinc-doped phosphosilicate glasses [Articolo su rivista]
Lusvardi, Gigliola; Zaffe, Davide; Menabue, Ledi; Bertoldi, Carlo; Malavasi, Gianluca; Consolo, Ugo
abstract

The aim of this work was to study the behaviour of zinc-doped phosphosilicate glasses based on Bioglass 45S5. In vitro (in simulated body fluid), the reactivity was analysed by means of inductively coupled plasma spectrometry, environmental scanning electron microscopy–energy-dispersive spectroscopy (ESEM–EDS) and X-ray diffraction. In vivo (a rat implanted with glass), the reactivity and the tissue behaviour were analysed by conventional histology, histochemistry, microradiography and ESEM–EDS. The in vivo behaviour matches that in vitro perfectly; they show comparable glass degradation processes and rates, ruled by the amount of zinc in the glass.The reaction mechanism for the formation of a polymerized silica layer superimposed with a peripheral calcium phosphate layer is clearly substantiated by ESEM–EDS investigations. The crystallization of a biologically active hydroxyapatite (HA) layer is observed in both cases; the in vitro experiment shows the presence of HA after 4 days. IDS Number: 386ZV PMID: 18701362

2009 - Morphologic, histochemical, and functional analysis of platelet-rich plasma activity on skeletal cultured cells [Articolo su rivista]
Bertoldi, Carlo; Pinti, Marcello; Zaffe, Davide; Cossarizza, Andrea; Consolo, Ugo; G. B., Ceccherelli
abstract

BACKGROUND:Platelet-rich plasma (PRP) is a medium containing concentrated amounts of growth factors in a form that is easy to handle in regenerative sites. The aim of this study was to assess the effect of PRP on the differentiation of cultured skeletal cells and the capability of PRP to induce the production of some osteogenesis-related molecules and mineralization.STUDY DESIGN AND METHODS:Flow cytometry (cellular antigens), real-time quantitative polymerase chain reaction (RT-qPCR; bone morphogenetic protein [BMP] messengers), alkaline phosphatase (ALP; osteogenic expression), and calcification analyses were performed on 24- and 48-hour human bone cells (HBCs) and 143B and SaOS-2 (osteosarcoma) cell cultures to study the effect of PRP on proliferation and differentiation of skeletal cultured cells. PRP was added using different protocols since no studies are available on bone cultures treated in the long term with PRP.RESULTS:Flow cytometry showed PRP induction toward a nonhemopoietic lineage in HBCs; RT-qPCR showed enhanced mRNA encoding for BMP2 in HBCs, BMP6 and BMP7 in 143B cultures, and BMP2 and BMP7 in SaOS-2 cultures. Better ALP and calcification results were obtained in SaOS-2 cultures when PRP was added more frequently at shorter intervals while poor results were obtained after single PRP addition.CONCLUSIONS:The results highlight induction of bone cell proliferation and differentiation by PRP. Since repeated administration of PRP is needed to achieve the best results, an almost continuous delivery system of PRP, or better a controlled release of growth and differentiation factors, using biomaterials might provide increased performance at bone regeneration sites. IDS Number: 478LS PMID: 19413738

2009 - Studio longitudinale sul ruolo dei disturbi della personalità, di ansia e depressione nei risultati terapeutici conseguenti alla terapia parodontale causale in soggetti non parodontici [Articolo su rivista]
Bertoldi, Carlo; Guaitolini, S.; Venuta, M.; Lucchi, A.; Lalla, Michele; Veneziani, A.; Zaffe, Davide; Consolo, Ugo; Guaraldi, G.
abstract

Introduzione e scopo: L’insorgenza della parodontite è quanto meno facilitata se non dovuta alla presenza di fattori di rischio parodontali. Tra i fattori di rischi putativi (non comprovati ma presunti) di maggior interesse scientifico stanno quelli legati ai profili psicologico-comportamentali. Scopo del presente studio sarà quello di analizzare il ruolo dei fattori psicologici nell’insorgenza della parodontite. Materiali e metodi: 13 individui (4 di sesso femminile e 9 di sesso maschile) maggiorenni, sistemicamente e psichiatricamente sani, non affetti da malattia parodontale erano stati selezionati per lo studio. Il protocollo operativo comprendeva 4 fasi: visita, terapia causale, rivalutazione parodontale e terapia di mantenimento. Al soggetto, durante la prima fase, era richiesta la compilazione di un questionario di igiene-consapevolezza al fine di valutare la sua conoscenza delle procedure di igiene dentale domiciliare, professionale e di conoscere i procedimenti domiciliari da esso stesso portati in atto routinariamente. Venivan, inoltre, registrati il full-mouth bleeding score (FMBS), il full-mouth plaque score (FMPS) ed il peridontal screening and recording (PSR). Nel caso il paziente fosse incluso nello studio era richiesta anche la compilazione di 3 appositi test psicologici: diagnostic and statistical manual of mental disorders (DSM-SCID) – valutazione del tratto della personalità, il depression status inventory (DSI) ed il self-rating depression scale (SDS) per definire rispettivamente il grado di ansia e depressione del paziente. I pazienti erano quindi immessi interapia causale e seguiti per un follow-up complessivo di 18 mesi con rivalutazione degli indici parodontali ogni 3 mesi. Risultati: L’elaborazione dei dati mediante coefficienti di relazione hanno mostrato andamenti clinici favorevoli in coloro che maggiormente attuavano e conoscevano le procedure di igiene orale mentre tratti ansioso-depressivi si correlavano longitudinalmente a indici peggiori di FMPS me non di FMBS. Nello stesso tempo la valutazione multivariata degli indici ha indicato come ai disturbi ansiogeni o depressivi si sono ricavati risultati favorevoli in rapporto ai comportamenti igienici riferiti come attuati o da attuarsi e sfavorevoli in rapporto all’FMPS e, talora ai comportamenti igienici attuati con continuità. Conclusioni: Dai dati emersi dall’elaborazione di questo studio appare che le personalità ansiose e depressive attuano principalmente comportamenti igienici discontinui potenzialmente in grado di favorire l’insorgenza della malattia parodontale. Non si può, tuttavia, escludere in termini assoluti altre cause endogene legate alla mediazione della flogosi ed all’immunità.

2009 - Vagus nerve mediates the protective effects of melanocortins against cerebral and systemic damage after ischemic stroke. [Articolo su rivista]
Ottani, Alessandra; Giuliani, Daniela; Mioni, C; Galantucci, M; Minutoli, L; Bitto, A; Altavilla, D; Zaffe, Davide; Botticelli, Ar; Squadrito, F; Guarini, Salvatore
abstract

A vagus nerve-mediated, efferent cholinergic protective pathway activated by melanocortins is operative in circulatory shock and myocardial ischemia. Moreover, melanocortins have neuroprotective effects against brain damage after ischemic stroke. Here we investigated cerebral and systemic pathophysiologic reactions to focal cerebral ischemia in rats induced by intrastriatal microinjection of endothelin-1, and the possible protective role of the melanocortin-activated vagal cholinergic pathway. In the striatum and liver of saline-treated control rats, the activation of extracellular signal-regulated kinases, c-jun N-terminal kinases, and caspase-3, the increase in tumor necrosis factor-α (TNF-α) concentration and DNA fragmentation, as well as the increase in TNF-α plasma levels, occurred 10 and 20 h after the ischemic insult suggesting an activation of inflammatory and apoptotic responses. Treatment with [Nle4, D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH; 3 or 9 h after stroke) suppressed the inflammatory and apoptotic cascades at central and peripheral level. Bilateral vagotomy and pharmacologic blockade of peripheral nicotinic acetylcholine receptors blunted the protective effect of NDP-α-MSH. The present results show that focal brain ischemia in rats causes significant effects not only in the brain, but also in the liver. Moreover, our data support the hypothesis that a protective, melanocortin-activated, vagal cholinergic pathway is likely operative in conditions of ischemic stroke.

2008 - Alveolar distraction osteogenesis: histo-densitometric evaluation. [Abstract in Rivista]
Bertoldi, Carlo; Bellini, Pierantonio; Landini, B.; Zaffe, Davide
abstract

Vedi allegato

2008 - Biomechanical aspects in dental replacements [Capitolo/Saggio]
Baldini, Andrea; Bruzzesi, G.; Zaffe, Davide; Giacopini, Matteo; Strozzi, Antonio; DE POL, Anto
abstract

This chapter deals with biomechanical aspects in dental replacements. The state of the art is critically reviewed taking into account the body of the literature results. The initial section is devoted to the mechanical properties of bone and to a description of the jaw geometry and of its loading and constraining. The following section presents a classifi cation of the various tooth replacement confi gurations and of the various materials adopted, where single and multiple replacements are considered. A specifi c section is devoted to the solid modelling of the jaw as input to numerical analyses, where the aid offered by reverse engineering and tomography is underlined. The fi nite element method as well as alternative numerical and experimental approaches are reviewed in a dedicated section. The stress analysis forecasts and measurements are biomechanically interpreted in the light of the current literature results. The chapter ends with a section devoted to biological aspects.

2008 - Derivati proteici della matrice dello smalto ed il condizionamento radicolare mediante gel di acido etilendiamminotetraacetico nel trattamento rigenerativo dei difetti intraossei con principi di chirurgia minimamente invasiva: uno studio pilota. [Articolo su rivista]
Bertoldi, Carlo; Zaffe, Davide; Bencivenni, D.; Giannetti, Luca; Lucchi, A.; Consolo, Ugo
abstract

Scopo del presente studio pilota, randomizzato e controllato è quello di comparare l’efficacia del condizionamento radicolare mediante acido etilendimminotetracetico (EDTA) nel trattamento di difetti intraossei profondi in termini di riduzione radiografica del difetto utilizzando tecniche di chirurgia minimamente invasiva. Materiali e Metodi: Sono stati inclusi nello studio 8 pazienti sistemicamente sani, di età media di 40,88 ± 7,2 (compresa tra i 29 i 49 anni), nel gruppo TG1 l’età media era 40,05 ± 9,7 mentre net TG2 era 41,25 ± 5,1. I pazienti venivano scelti tra coloro che soffrivano di parodontite cronica moderata o grave. I soggetti selezionati dovevano presentare almeno un difetto intraosseo angolare maggiore di 6 mm al sondaggio (PPD) e con una componente intraossea radiologica maggiore a 3 mm. L’angolo del difetto doveva essere inferiore a 36°. Il difetto, inoltre, doveva avere una preponderante componente a 3 e a 2 pareti. Lo studio poneva a confronto 2 differenti metodologie di trattamento; lo stesso accesso chirurgico, basato su principi di chirurgia minimamente invasiva e preservazione papillare, veniva attuato su difetti intraossei angolari. La scelta dei soggetti e quindi dei siti che dovevano essere sottoposti a condizionamento preventivo all’applicazione dei EMP (PrefGel & Emdogain, Straumann, Basel, Switzerland) con gel di EDTA al 24% (pH 6,7) (trattamento gruppo 1 - TG1) secondo le istruzioni del produttore e di quelli che sarebbero stati trattati con EMP senza preventivo condizionalmento (trattamento gruppo 2 – TG2), era basata su un criterio di randomizzazione semplice. Le misurazioni radiologiche, che costituiscono la base sperimentale del presente studio, erano eseguite mediante un centratore (Rinn, Dentsply, Weybridge, UK) reso individuale mediante un “bite” in silicone. Le valutazioni erano eseguite in fase iniziale (fase T0), immediatamente dopo l’intervento (T1), a 1 mese (T2) ed a 6 mesi dall’intervento (T3). Venivano registrate le seguenti misure lineari: - Profondità della componente intraossea del difetto (IBC) considerandola come la distanza verticale intercorrente (in mm) dalla cresta ossea al punto più apicale del difetto - Angolo del difetto (DA); misurato in gradi e definito come l’angolo compreso tra il profilo della radice e la parete verticale ossea del difetto. Risultati: Confrontando orizzontalmente, in rapporto all’IBC, i gruppi TG1 e TG2 tra loro nella fase iniziale (T0) così come nelle diverse fasi successive (T1, T2 e T3), il valore di P rimaneva maggiore di 0,06 per cui non si rilevavano tra essi differenze statisticamente significative. L’indagine statistica longitudinale attuata su TG1 presentava risultati significativi solo tra T1 e T4; lo stesso risultato statistico si otteneva dall’analoga valutazione del TG2. Conclusioni: In questo studio pilota si è deciso di valutare a 6 mesi unicamente il parametro radiologico poiché alcune indicazioni sono emerse del tutto recentemente circa la possibile compromissione dei risultati rigenerativi conseguibili operando dei sondaggi antecedentemente ad un anno dall’intervento. Nel nostro studio abbiamo ottenuto risultati favorevoli a 6 mesi con entrambe le metodologie di intervento. Pur con i limiti insiti in uno studio pilota, i risultati emersi depongono per una “tendenza” rigenerativa decisamente marcata a 6 mesi dall’intervento mentre il potenziale contributo del condizionamento radicolare con gel di EDTA sulla rigenerazione della quota calcifica del difetto intraosseo non sembra significativo.

2008 - Derivati proteici della matrice dello smalto ed osso poroso di derivazione bovina nel trattamento rigenerativo dei difetti intraossei con principi di chirurgia minimamente invasiva: uno studio pilota. [Articolo su rivista]
Bertoldi, Carlo; Zaffe, Davide; Lucchi, A.; Giannetti, Luca; Consolo, Ugo
abstract

Scopo del presente studio pilota, randomizzato e controllato è quello di comparare l’efficacia clinica dei soli derivati proteici della matrice dello smalto (EMP) rispetto all’associazione di EMP e derivati xenografici di osso bovino (BPBM) nel trattamento di difetti intraossei profondi in termini di riduzione radiografica del difetto utilizzando tecniche di chirurgia minimamente invasiva. Materiali e Metodi: Sono stati inclusi nello studio 4 pazienti, di età media di 54,75 ± 7,9 (compresa tra i 44 e i 62 anni), due di sesso maschile e due di sesso femminile con difetti angolari soddisfacenti i criteri di inclusione in tutti i casi a livello premolare. I pazienti venivano scelti tra coloro che soffrivano di parodontite cronica moderata o grave. Lo studio a split-mouth poneva a confronto 2 differenti strategie di trattamento; lo stesso accesso chirurgico, basato su principi di chirurgia minimamente invasiva e preservazione papillare, veniva attuato su difetti intraossei angolari nell’ambito della stessa arcata ma a split-mouth. La scelta del sito che doveva essere trattato con EMP (trattamento gruppo 1 - TG1) e, di conseguenza, di quello controlaterale trattato con EMP + BPBM (trattamento gruppo 2 – TG2), era basata su un criterio di randomizzazione semplice. Le misurazioni radiologiche, che costituiscono la base sperimentale del presente studio, erano eseguite mediante un centratore (Rinn, Dentsply, Weybridge, UK) reso individuale mediante un “bite” in silicone. Le valutazioni erano eseguite in fase iniziale (fase T0), immediatamente dopo l’intervento (T1), a 1 mese (T2) ed a 6 mesi dall’intervento (T3). Venivano registrate le seguenti misure lineari: - Profondità della componente intraossea del difetto (IBC) considerandola come la distanza verticale intercorrente (in mm) dalla cresta ossea al punto più apicale del difetto - Angolo del difetto (DA); misurato in gradi e definito come l’angolo compreso tra il profilo della radice e la parete verticale ossea del difetto. Risultati: L’analisi dei valori di IBC durante le fasi operative successive al baseline (dove vi era sovrapponibilità statistica tria i 2 gruppi) dava i seguenti risultati: in faseT0 non rilevava significatività statistica tra TG1 e TG2, tale significatività era, invece, presente in fase T1 e T2 e, di nuovo, non si rilevava significatività in fase T3. L’indagine longitudinale rispetto ai differenti gruppi presentava risultati significativi sia per TG1 che per TG2. Analizzando in dettaglio il risultato mediante test per confronti multipli risultava che nel TG1 si rilevava differenza significativa la fase T0 e la fase T3 e tra la fase T1 e la T3. Per quanto riguarda invece TG2 si verificavano differenze significative tra la fase T0 e la T1, tra la T0 e la T2 ma non per altre combinazioni di fasi come, ad esempio, tra T0 e T3. Conclusioni: Nel nostro studio abbiamo ottenuto risultati favorevoli a 6 mesi con entrambe le tipologie di innesto. In TG1, nella fase T1, in termini assoluti e senza rilevanza statistica, si osservano risultati peggiori rispetto a T0; i valori, poi, migliorano sino a T3, fase in cui non si osservano significatività statistiche rispetto a T3 di TG2. In quest’ultimo gruppo, viceversa, in T1 si assiste a risultati, in termini assoluti, migliori che a T3, senza che, tuttavia, vi siano significatività statistiche nella comparazione tra T1 con T3 per TG2. I risultati emersi si sono dimostrati assai interessanti in quanto si è osservato che i soli EMP sarebbero in grado di garantire risultati radiologici sovrapponibili a quelli ottenibili con i BPBM in rapporto però a ben precise tipologie di difetto e con tecniche chirurgiche metodologicamente avanzate

2008 - Extracorporeal hydroxyapatite-chamber for bone and biomaterial studies [Articolo su rivista]
Tarallo, Luigi; Zaffe, Davide; Adani, Roberto; Krajewski, A.; Ravaglioli, A.
abstract

Hydroxyapatite (HA) spherules and autologous bone (AB) with a central vascular pedicle were housed inside an HA-chamber to form the skeletal segment of specific shape. Experimental chambers were then inserted in a pocket between medial thigh muscles in 13 New Zealand male rabbits for 3 months. Three graft group were scheduled: (A) HA and AB without vascular pedicle, (B) HA with vascular pedicle, (C) HA and AB with vascular pedicle. At term, histology showed tissue and cellular degeneration in group A chambers. Due to spherules coalescence, fibrous tissue is formed in group B chambers. Group C chambers contained living osteocytes in the implanted bone, several newly formed vessels in soft tissue, bone and partial hydroxyapatite erosions. New bone was formed in apposition to both autologous bone and hydroxyapatite. Our study suggests that this experimental model could be used to grow adequately sized vascularized skeletal segments.

2008 - La guarigione delle ferite [Capitolo/Saggio]
N., Cocero; R., Pol; Zaffe, Davide
abstract

Capitolo sulla biologia, patologia e clinica delle guarigioni delle ferite e dell'alveolo postestrattivo

2008 - Nuovi vetri bioattivi contenenti zinco. [Relazione in Atti di Convegno]
Bertoldi, Carlo; Zaffe, Davide; Lusvardi, Gigliola; Pellacani, C.; Consolo, Ugo
abstract

Vedi allegato

2008 - Polylactide/polyglycolide copolymer in bone defect healing in humans. [Articolo su rivista]
Bertoldi, Carlo; Zaffe, Davide; Consolo, Ugo
abstract

This pilot study aims to evaluate the healing of a large defects in the human jawbone filled with a Poly-Lactide-co-Glycolide (PLG) polymer (Fisiograft) by means of clinical, radiological and histological methods and to compare the results with those of platelet-rich plasma (PRP) clot or autologous bone (AB) fillings. Bone cysts, where previous non-surgical treatments failed to promote healing, underwent surgery. Nineteen consenting male patients were randomly split into three groups, packed with PRP, AB or PLG. A core biopsy was performed 4 and 6 months after surgery. All treated defects showed clinical, radiological and histological progresses over time. AB provided the best clinical and histological performance and PLG had overlapping outcomes; PRP filling was statistically different. Six months after surgery, bone activities were enhanced in sites treated with PLG and fairly good with PRP. Additionally, PLG showed some new lamellar formations. In conclusion, outcomes were best with AB graft, but suitable results were achieved using PLG to promote healing of severe bone defects. PLG shows only a delayed regenerative capability but does not require a secondary donor site. IDS Number: 284TV PMID: 18234328

2008 - Vetri bioattivi con elementi stimolanti l’osteogenesi: primi risultati nel ratto [Articolo su rivista]
Bertoldi, Carlo; Zaffe, Davide; Consolo, Ugo; Lusvardi, Gigliola; A., Lucchi; Menabue, Ledi
abstract

Introduzione e scopo: Numerose composizioni di vetri bioattivi sono state proposte dopo l'iniziale biovetro di Hench presentato negli anni '70. In realtà il range di variazione della composizione di un vetro bioattivo è abbastanza ridotto soprattutto in rapporto ai suoi elementi pesanti si vuole mantenere l'effetto osteoinduttivo. Ciò in particolarmente in rapporto allo zinco che ne costituisce una fase critica sia da un punto di vista chimico che biologico.Un problema manifestato dal vetro di Hench era quello di agire con buona performance ma di esaurire in fretta la sua azione. Scopo della nostra ricerca preliminare è di studiare il comportamento di vetri contenenti zinco a seguito di impianto degli stessi su modelli biologici standardizzati (muscoli paravertebrali e calvaria di ratto) e di confrontarlo con quello conseguito all’innesto del biovetro di Hench. Materiali e metodi: Vetri bioattivi modificati, derivanti dal bio-glass ® 45S5 di Hench sono stati prima testati chimicamente al fluido biologico somulato con spettroscopia al plasma e analisi diffrattometrica X. Impiantati in 10 ratti maschi Sprague Dawley in forma di polvere e cilindri nei muscoli paravertebrali ed in forma di placchette in difetti critici prodotti sulla calvaria. Sono state analizzati a split-back e su calvaria vetri con concentrazioni al 5% e 20% di zinco e vetro di Hench. Gli animali sono stati sacrificati a 30 giorni dall’intervento e sono state eseguite analisi microradiografiche, al microscopio elettronico a scansione ed istologiche. Risulatati: La diffusione degli ioni zinco si dimostrava assolutamente contenuta allo studio spettroscopico e diffrattomentrico mentre clinicamente gli animali non presentavano reazioni patologiche rilevanti all’innesto. I campioni contenenti un maggior contenuto di zinco parevano essere meno soggetti a degradazione rispetto agli altri e le forme granulari erano degradate con maggior velocità rispetto a quelle compatte. La presenza di uno strato positivo alla fosfatasi alcalina in rapporto alla superficie del biovetro assieme alla deposizione di strati di connettivo presumibilmente osteogenico uniformano sostanzialmente il comportamento dei vetri testati ed il loro potenzaile osteogenetico. Conclusione: La presenza di zinco (almeno fino alle concentrazioni testate) nel vetro pare essere inversamente proporzionale alla reattività dello stesso per cui l’utilizzazione di questo ione pare essere funzionale nel regolare i tempi di bioattività dello stesso vetro senza pesare significativamente sulla biocompatibilità degli stessi preparati.

2007 - A novel bone scraper for intraoral harvesting: a device for filling small bone defects [Articolo su rivista]
Zaffe, Davide; F., D'Avenia
abstract

Aim: To evaluate histologically the morphology and characteristics of bone chips harvested intraorally by Safescraper (R), a specially designed cortical bone collector.Material and methods: Bone chips harvested near a bone defect or in other intraoral sites were grafted into a post-extractive socket or applied in procedures for maxillary sinus floor augmentation or guided bone regeneration. Core biopsies were performed at implant insertion. Undecalcified specimens embedded in PMMA were studied by histology, histochemistry and SEM.Results: Intraoral harvesting by Safescraper (R) provided a simple, clinically effective regenerative procedure with low morbidity for collecting cortical bone chips (0.9-1.7 mm in length, roughly 100 mu m thick). Chips had an oblong or quadrangular shape and contained live osteocytes (mean viability: 45-72%). Bone chip grafting produced newly formed bone tissue suitable for implant insertion. Trabecular bone volume measured on biopsies decreased with time (from 45-55% to 23%). Grafted chips made up 50% or less of the calcified tissue in biopsies. Biopsies presented remodeling activities, new bone formation by apposition and live osteocytes (35% or higher).Discussion and conclusions: In conclusion, Safescraper (R) is capable of collecting adequate amounts of cortical bone chips from different intraoral sites. The procedure is effective for treating alveolar defects for endosseous implant insertion and provides good healing of small bone defects after grafting with bone chips. The study indicates that Safescraper (R) is a very useful device for in-office bone harvesting procedures in routine peri-implant bone regeneration.

2007 - Architettura e funzione del miocardio. Consensi, controversie e incognite [Articolo su rivista]
Zaffe, Davide; Lodi, Renzo
abstract

La disposizione tridimensionale dell’architettura ventricolare del muscolo miocardico, nonostante l’intenso lavoro di ricerca anatomica svolto nel tempo, presenta ancora numerosi aspetti poco chiari e controversi, soprattutto in relazione alla conoscenza dei rapporti tra l’organizzazione dei miocardiociti e le funzioni del cuore. Le ragioni delle incognite sono dovute al fatto che la morfologia strutturale del miocardio non si presta ad una agevole interpretazione, e che la tecnica della dissezione anatomica della massa muscolare ventricolare, cioè il metodo di indagine maggiormente utilizzato, è in gran parte distruttivo per cui non consente ulteriori studi. È da tempo accettato dalla maggior parte degli Anatomisti che le fibre muscolari ventricolari siano organizzate secondo un sistema sinciziale. La natura della struttura e dell’architettura miocardica, nel corso degli anni, è stata variamente interpretata dai Fisiologi, dai Cardiologi e dai Cardiochirurghi, con diverse riserve concettuali circa gli aspetti interrelazionali tra struttura, architettura e funzioni del miocardio ventricolare. Più recentemente è stata ipotizzata una nuova concezione architetturale tridimensionale originale della massa ventricolare cardiaca. Uno studioso spagnolo, Torrent-Guasp, basandosi su un criterio di continuità anatomica, ha avanzato l’ipotesi della esistenza di un’unica banda muscolare ventricolare disposta a spirale (Helical Ventricular Myocardial Band), che potrebbe consentire una migliore interpretazione delle funzioni cardiache. In questa revisione gli Autori focalizzano l’attenzione su una sintesi del lavoro anatomico finora compiuto nell’intento di puntualizzare lo stato delle conoscenze relative ai rapporti tra struttura, architettura e funzioni del miocardio. Queste conoscenze assumono un interesse fondamentale ai fini dell’applicazione di adeguati trattamenti e tecniche chirurgiche correttive delle diverse patologie cardiache e dei risultati che ne conseguono.

2007 - Azione neuroprotettiva dei peptici melanocortinici nell’ictus ischemico sperimentale [Articolo su rivista]
Giuliani, Daniela; Mioni, C.; Bazzani, Carla; Ottani, Alessandra; Galantucci, M.; Zaffe, Davide; Botticelli, A. R.; Lodi, Renzo; Guarini, Salvatore
abstract

L’ictus ischemico è una delle cause principali di disabilità e di morte nei paesi occidentali. Negli ultimi anni abbiamo dimostrato che dosi nanomolari di peptidi melanocortinici, somministrati per via sistemica nel gerbillo e nel ratto, promuovono (verosimilmente in modo definitivo) il recupero funzionale dopo un attacco ischemico cerebrale globale o focale. Infatti, il trattamento con [Nle4, D-Phe7]--MSH (NDP--MSH, agonista sintetico dei recettori melanocortinici MCI, MC3, MC4 e MC5), causa una riduzione della risposta infiammatoria, come indicato dalla diminuzione dell’attività dei fattori regolatori della trascrizione JNKs, p38 ed ERKs, e dei livelli delle citochine proinfiammatorie TNF- (tumour necrosis factor-) e interleukina-6 (IL-6); NDP- -MSH riduce anche l’attività della caspasi-3 (proteina proapoptotica effettrice) e la frammentazione del DNA nelle aree cerebrali danneggiate. Inoltre, NDP--MSH dimostra un’ampia finestra terapeutica, infatti il trattamento è efficace anche quando inizia 12 ore dopo l’insulto ischemico e probabilmente 18 ore sono il tempo limite per la somministrazione del neuropeptide. I meccanismi di neuroprotezione sembrano coinvolgere direttamente I’attivazione dei recettori melanocortinici MC4, Infatti, il blocco farmacologico di questi recettori non solo previene l’effetto neuroprotettivo dell' NDP-a-MSH, ma addirittura peggiora il recupero funzionale. I nostri dati suggeriscono che agonisti melanocortinici, ahmente selettivi per i recettori MC4 e capaci di superare la barriera ematoencefalica, potrebbero rappresentare il mezzo per un approccio più mirato, innovativo e sicuro nell'ictus umano.

2007 - Biocompatibilità di nuovi vetri bioattivi contenenti zinco. [Relazione in Atti di Convegno]
Bertoldi, Carlo; Zaffe, Davide; Lusvardi, Gigliola; Consolo, Ugo; Menabue, Ledi
abstract

Vedi allegato

2007 - Neuroprotection in focal cerebral ischemia owing to delayed treatment with melanocortins. [Articolo su rivista]
Giuliani, Daniela; Ottani, Alessandra; C., Mioni; Bazzani, Carla; M., Galantucci; L., Minutoli; A., Bitto; Zaffe, Davide; A. R., Botticelli; F., Squadrito; Guarini, Salvatore
abstract

In gerbils subjected to transient global cerebral ischemia, melanocortin peptides produce long-lasting protection with a broad time window, and through the activation of central nervous system melanocortin MC(4) receptors. Here we aimed to investigate whether melanocortins are neuroprotective also in a rat model of focal cerebral ischemia induced by intrastriatal microinjection of endothelin-1. The vasoconstrictor agent endothelin-1 caused a significant impairment in spatial learning and memory, as well as in sensory-motor orientation and limb use, associated with severe striatal morphological damage including intense neuronal death and an almost complete myelin degradation. Treatment of ischemic rats with a nanomolar dose (340 mug/kg/day i.p. for 11 days, beginning 3 h or 9 h after endothelin-1 microinjection) of the melanocortin analog [Nle(4), d-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) significantly reduced striatal damage, and improved subsequent functional recovery, with all scheduled NDP-alpha-MSH treatments. Pharmacological blockade of melanocortin MC(4) receptors prevented the protective effect of NDP-alpha-MSH. Our findings give evidence that melanocortins are neuroprotective, with a broad time window, also in a severe model of focal cerebral ischemia, and suggest that melanocortin MC(4) receptor agonists could produce neuroprotection in different experimental models of ischemic stroke.

2007 - Plasma arricchito di piastrine nel rialzo del seno mascellare. Studio preliminare [Articolo su rivista]
Consolo, Ugo; Zaffe, Davide; Bertoldi, Carlo; Ceccherelli, G; Bellini, Pierantonio
abstract

Questo studio preliminare ha inteso valutare il potenziale rigenerativo del platelet-rich plasma (PRP) in un sito peculiare: il seno mascellare.Quattro pazienti consenzienti (3 di sesso femminile e 1 di sesso maschile), con atrofia simmetrica del pavimento sinusale, sono stati sottoposti a sinus lift utilizzando osso autologo (cresta iliaca) da solo in un lato e addizionato a PRP nell’altro. Ortopantomografia, TC e analisi densitometrica e valutazioni cliniche vennero utilizzate per seguire l’.evoluzione dell’innesto. Impianti furono inseriti a 4 mesi dall’intervento di sinus lift, eseguendo anche una biopsia per ciascun sito. I valori densitometrici medi risultavano più elevati nei siti trattati con PRP anche se la valutazione clinica complessiva non forniva risultati statisticamente differenziabili. Le biopsie evidenziavano la presenza di una maggiore quantità ossea e una maggior espressione dell’attività fosfatasica alcalina nei siti trattati con PRP. In conclusione i risultati sembrerebbero indicare che il PRP abbia un’ azione amplificante sull’attività osteogenica dell’osso autologo. Ulteriori studi dovranno essere attuati per verificare gli effetti del PRP nel tempo ed il suo effettivo impatto clinico.

2007 - Platelet-rich plasma activity on maxillary sinus floor augmentation by autologous bone. [Articolo su rivista]
Consolo, Ugo; Zaffe, Davide; Bertoldi, Carlo; Giovanni, Ceccherelli
abstract

OBJECTIVES: This work aims to evaluate the regenerative potential of platelet-rich plasma (PRP) on an implant site of peculiar clinical impact, such as sinus augmentation. MATERIAL AND METHODS: Sixteen consenting patients (11 females and five males), with symmetrical maxillary sinus atrophy, underwent bilateral sinus floor augmentation, using autologous (iliac crest) bone on one side and PRP plus autologous bone contralaterally. Implants were inserted 4, 5, 6 and 7 months after surgery in the patients randomly split into four groups. Orthopantomographies, computed tomography with transverse image digital reconstructions and densitometries were used to monitor the treatment progress. A core biopsy was performed at the site of implant. RESULTS: Clinical performance across both sites showed no statistical significance (P=0.414). Densitometric values were higher at PRP sites (mean Hounsfield units approximately +57\%), even if densitometry converged in the two sites 8 months after surgery. Histology documents enhanced bone activities in sites treated with PRP, 4 months after surgery. Reduced bone activity was observed in both sites 5, 6 and 7 months after surgery. Bone amount, higher in sites treated with PRP (mean trabecular bone volume approximately +37\%), decreased in both sites over time. CONCLUSIONS: Our results seem to indicate a certain regenerative potential of PRP when used with autologous bone. The effect of this enhancement of bone regeneration appeared to be restricted to shorter treatment times. A progressive extinguishment of the PRP effect is recorded after an interval longer than 6-7 months. IDS Number: 143JW PMID: 17348891

2007 - Selective melanocortin MC4 receptor agonists reverse haemorrhagic shock and prevent multiple organ damage [Articolo su rivista]
Giuliani, Daniela; C., Mioni; Bazzani, Carla; Zaffe, Davide; A. R., Botticelli; S., Capolongo; A., Sabba; M., Galantucci; Iannone, Anna; P., Grieco; E., Novellino; G., Colombo; Tomasi, Aldo; A., Catania; Guarini, Salvatore
abstract

Background and purpose: In circulatory shock, melanocortins have life-saving effects likely to be mediated by MC4 receptors. To gain direct insight into the role of melanocortin MC4 receptors in haemorrhagic shock, we investigated the effects of two novel selective MC4 receptor agonists. Experimental approach: Severe haemorrhagic shock was produced in rats under general anaesthesia. Rats were then treated with either the non-selective agonist [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) or with the selective MC4 agonists RO27-3225 and PG-931. Cardiovascular and respiratory functions were continuously monitored for 2 h; survival rate was recorded up to 24 h. Free radicals in blood were measured using electron spin resonance spectrometry; tissue damage was evaluated histologically 25 min or 24 h after treatment. Key results: All shocked rats treated with saline died within 30-35 min. Treatment with NDP-alpha-MSH, RO27-3225 and PG-931 produced a dose-dependent (13-108 nmol kg(-1) i.v.) restoration of cardiovascular and respiratory functions, and improved survival. The three melanocortin agonists also markedly reduced circulating free radicals relative to saline-treated shocked rats. All these effects were prevented by i.p. pretreatment with the selective MC4 receptor antagonist HS024. Moreover, treatment with RO27-3225 prevented morphological and immunocytochemical changes in heart, lung, liver, and kidney, at both early (25 min) and late (24 h) intervals. Conclusions and Implications: Stimulation of MC4 receptors reversed haemorrhagic shock, reduced multiple organ damage and improved survival. Our findings suggest that selective MC4 receptor agonists could have a protective role against multiple organ failure following circulatory shock.

2006 - Bio-oss ed idrossiapatite nella riparazione di difetti ossei: studio preliminare. [Abstract in Rivista]
Bertoldi, Carlo; Zaffe, Davide; Bellini, Pierantonio; Giannetti, Luca; Consolo, Ugo
abstract

Vedi allegato

2006 - Both early and delayed treatment with melanocortin 4 receptor-stimulating melanocortins produces neuroprotection in cerebral ischemia [Articolo su rivista]
Giuliani, Daniela; Mioni, C.; Altavilla, D.; Leone, S.; Bazzani, Carla; Minutoli, L.; Bitto, A.; Cainazzo, M. M.; Marini, H.; Zaffe, Davide; Botticelli, A. R.; Pizzala, R.; Savio, M.; Necchi, D.; Schioth, H. B.; Bertolini, Alfio; Squadrito, F.; Guarini, Salvatore
abstract

Ischemic stroke is one of the main causes of death and disability. We investigated whether melanocortin peptides, which have protective effects in severe hypoxic conditions, also produce neuroprotection in a gerbil model of ischemic stroke. A 10-min period of global cerebral ischemia, induced by occluding both common carotid arteries, caused impairment in spatial learning and memory that was associated with activation of inflammatory and apoptotic pathways, including severe DNA damage and delayed neuronal death, in the hippocampus. Treatment with nanomolar doses of the melanocortin analog [Nle(4), D-Phe(7)] alpha-MSH [which activates the melanocortin receptor subtypes ( MC) mainly expressed in central nervous system, namely MC3 and MC4] modulated the inflammatory and apoptotic cascades and reduced hippocampus injuries even when delayed up to 9 h after ischemia, with consequent dose-dependent improvement in subsequent functional recovery. The selective MC3 receptor agonist gamma(2)-MSH had no protective effects. Pharmacological blockade of MC4 receptors prevented the neuroprotective effects of [Nle(4), D-Phe(7)] alpha-MSH and worsened some ischemia outcomes. Together, our findings suggest that MC4 receptor-stimulating melanocortins might provide potential to develop a class of drugs with a broad treatment window for a novel approach to neuroprotection in ischemic stroke.

2006 - Broad therapeutic treatment window of [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone for long-lasting protection against ischemic stroke, in Mongolian gerbils [Articolo su rivista]
Giuliani, Daniela; Leone, S.; Mioni, C.; Bazzani, Carla; Zaffe, Davide; Botticelli, A. R.; Altavilla, D.; Galantucci, M.; Minutoli, L.; Bitto, A.; Squadrito, F.; Guarini, Salvatore
abstract

Melanocortin peptides have been shown to produce neuroprotection in experimental ischemic stroke. The aim of the present investigation was to identify the therapeutic treatment window of melanocortins, and to determine whether these neuropeptides chronically protect against damage consequent to brain ischemia. A 10-min period of global cerebral ischemia in gerbils, induced by occluding both common carotid arteries, caused impairment in spatial learning and memory (Morris test: four sessions from 4 to 67 days after the ischemic episode), associated with neuronal death in the hippocampus. Treatment with a nanomolar dose (340 mu g/kg i.p., every 12 h for 11 days) of the melanocortin analog [Nle(4), D-Phe(7)]alpha-metanocyte-stimulating hormone (NDP-alpha-MSH), starting 3-18 h after the ischemic episode, reduced hippocampal damage with improvement in subsequent functional recovery. The protective effect was long-lasting (67 days, at least) with all schedules of NDP-alpha-MSH treatment; however, in the latest treated (18 h) gerbils, some spatial memory deficits were detected. Pharmacological blockade of melanocortin MC4 receptors prevented the protective effects of NDP-alpha-MSH. Our findings indicate that, in conditions of brain ischemia, melanocortins can provide strong and longlasting protection with a broad therapeutic treatment window, and with involvement of melanocortin MC4 receptors, 18 h being the approximately time-limit for stroke late treatment to be effective.

2006 - Difetti cistici e trattamento con Fisiograft: studio pilota. [Abstract in Rivista]
Bertoldi, Carlo; Ciacci, L.; Bellini, Pierantonio; Zaffe, Davide; Consolo, Ugo
abstract

Vedi allegato

2006 - Espressione differenziale di BMPs in presenza di PRP: studio pilota. [Abstract in Rivista]
Bertoldi, Carlo; Pinti, Marcello; Cossarizza, Andrea; Zaffe, Davide; Consolo, Ugo
abstract

Vedi allegato

2006 - I neuropeptidi melanocortinici nell’approccio cardioprotettivo contro il danno da ischemia e da riperfusione [Articolo su rivista]
Mioni, C.; Giuliani, Daniela; Bazzani, Carla; Zaffe, Davide; Botticelli, A. R.; Bigiani, Albertino; Lodi, Renzo; Guarini, Salvatore
abstract

In questi ultimi anni abbiamo documentato che dosi nanomolari di melanocortine (neuropeptidi appartenenti al gruppo ACTH/MSH) hanno la capacità di attenuare in modo significativo, nel ratto, il danno conseguente ad ischemia/riperfusione miocardica e ad occlusione coronarica permanente, Dai nostri dati emerge che le melanocortine, previa stimolazione di recettorimelanocortinici MC3 localizzati nel sistema nervoso centrale, durante l’episodio ischemico innescherebbero l'attivazione di una via vagale efferente cardioprotettiva. La tappa finale di tale via cardioprotettiva sembra essere rappresentata dall’attivazione di recettori muscarinici periferici. I nostri dati suggeriscono che le melanocortine potrebbero fornire il potenziale per lo sviluppo di una nuova classe di farmaci per un approccio innovativo alla patologia ischemica cardiaca.

2006 - Impianti postestrattivi nei siti infetti [Articolo su rivista]
Leghissa, G. C; Redaelli, G; Zaffe, Davide; Botticelli, A. R.
abstract

N.D.

2006 - Intermittent loading improves results in mandibular alveolar distraction osteogenesis. [Articolo su rivista]
Consolo, Ugo; Bertoldi, Carlo; Zaffe, Davide
abstract

AIM: To evaluate clinical and morphological effects on distractive callus after application of an original protocol of bone stimulation. MATERIAL AND METHODS: Traditional or mechanically stimulated alveolar-distraction osteogenesis was studied on 16 highly selected subjects subdivided into two groups. Clinical, radiological, densitometric and histological (on biopsies) analyses were performed 6, 8 and 12 weeks after distraction was completed. RESULTS: In subjects undergoing stimulated alveolar-distraction osteogenesis, bone density was higher and at histology, bone with ordered structure was observed after 6 weeks. Moreover, bone trabeculae with oriented architecture and greater amounts of lamellar bone were observed after 8 and 12 weeks in the same subjects. DISCUSSION AND CONCLUSIONS: In conclusion, although osteogenic processes were similar in both groups, they were induced earlier and were better structured in subjects undergoing stimulated alveolar-distraction osteogenesis. These encouraging results can only be achieved and preserved by strict monitoring of distractive vectors. IDS Number: 020ER PMID: 16584414

2006 - La moda del piercing intraorale ed i rischi correlati. [Articolo su rivista]
Rizzo, S; Botticelli, A. R; Zaffe, Davide; Lupi, S. M; Rodriguez, Y. BAENA R.
abstract

Scopo del lavoro: Negli ultimi anni è andata diffondendosi la pratica del piercing anche nel cavo orale. Numerosi studi hanno valutato i possibili effetti collaterali sui tessuti duri e su quelli parodontali. Lo scopo di questa ricerca è valutare la presenza di alterazioni di tipo displastico nella struttura dei tessuti molli del cavo orale in seguito all’inserimento di piercing, per fare chiarezza sull’esistenza di un rischio reattivo iperplastico dovuto all’impianto di tali monili.Materiali e metodi: 14 volontari, portatori in totale di 15 piercing nel cavo orale, sono stati sottoposti al seguente iter diagnostico: 1) anamnesi generale e visita odontostomatologica; 2) fotografia delle sedi interessate; 3) prelievo mediante spatolamento di materiale cellulare attorno alla sede del piercing e deposizione su vetrino; 4) fissazione mediante Citofix; 5) studio citologico al microscopio ottico, previa colorazione di Papanicolau. Risultati: Sono state osservate, al momento della visita: 5 lesioni da decubito, 1 formazione cicatriziale, 1 caso di edema, 2 lesioni cariose, 1 abrasione, 1 affollamento dentario. Dall’esame citologico è emersa la presenza di colonie batteriche e fungine intracitoplasmatiche, granulocitosi, citolisi, paracheratosi dell’epitelio, lamine cornee, calcificazioni e corpi estranei.Conclusioni: L’esame citologico dei preparati mostra una estesa infezione da batteri e funghi, con colonizzazione e danneggiamento delle cellule superficiali. Il riscontro di paracheratosi dell’epitelio linguale starebbe a dimostrare una possibile alterazione della maturazione della porzione superficiale dell’epitelio di rivestimento. I risultati concordano con quelli della maggior parte degli Autori che indicano il rischio di infezione come una delle maggiori complicanze della pratica del piercing.

2006 - Melanocortins protect against myocardial ischemia/reperfusion injury through the activation of an efferent cholinergic pathway [Abstract in Atti di Convegno]
Giuliani, Daniela; Bazzani, Carla; Mioni, Chiara; Zaffe, Davide; Squadrito, F; Guarini, Salvatore
abstract

A vagus nerve-mediated brain cholinergic protective mechanism, is operative in circulatory schock. We investigated, therefore, role and functional mechanism of such vagal efferent pathway (s) in a model of ischemic heart disease. Anesthetized rats were subjected to transient coronary artery occlusion (5 min) followed by reperfusion: occurrence of ventricular tachycardia (VT), ventricular fibrillation (VF), and lethality, were recorded up to the 5th min after reperfusion. Electrical stimulation of efferent vagal fibres (5 V, 2 ms, 1-9 Hz, for the whole period of ischemia/reperfusion) reduced the high incidence of VT , VF and lethality, the increase in free radical blood levels and left ventricle histological alteration. Treatment with same melanocortin peptides (162 nmol/kg i.v. or 16.2 nmol/kgi.c.v.) produced the same protective effects of electrical stimulation, and with the same muscarinic receptor-dependent mechanism, seemingly through brain activation (mediated by melanocortin MC3 receptors) of such efferent vagal pathway. These findings could provide the potential for a novel approach to management of ischemic heart disease.

2006 - Physico-chemical characterization and in vivo evaluation of zinc-glasses biocompatibility [Capitolo/Saggio]
Lusvardi, Gigliola; Malavasi, Gianluca; Menabue, Ledi; Menziani, Maria Cristina; Pedone, Alfonso; Zaffe, Davide
abstract

Study of soda-lime-phosphosilicate glasses based on Bioglass® and modified by zinc. "In vitro"(SBF) bioactivity was investigated through apatite forming ability and through a preliminary "in vivo" study. Zinc improves chemical durability but does not inhibit the apatite formation; a mixed-metal (Ca-Zn) phosphate-based crystalline layer is identified on the surface of HP5Z5. The improvement of the observed chemical durability can also be rationalized by Molecular Dynamics simulations

2006 - Rialzo di cresta con materiale alloplastico [Articolo su rivista]
Leghissa, G. C; Redaelli, G.; Zaffe, Davide; Botticelli, A. R.
abstract

ND

2005 - Activation of an efferent cholinergic pathway produces strong protection against myocardial ischemia/reperfusion injury in rats [Articolo su rivista]
Mioni, C.; Bazzani, Carla; Giuliani, Daniela; Altavilla, D.; Leone, S.; Ferrari, Anna; Minutoli, L.; Bitto, A.; Marini, H.; Zaffe, Davide; Botticelli, Ar; Iannone, Anna; Tomasi, Aldo; Bigiani, Albertino; Bertolini, Alfio; Squadrito, F.; Guarini, Salvatore
abstract

Objective: A vagus nerve-mediated, brain cholinergic protective mechanism activated by melanocortin peptides is operative in conditions of circulatory shock; moreover, there is anatomical evidence of dual vagal-cardiac efferent pathways in rats, which could play different roles in controlling heart function. Therefore, we investigated the role and functional mechanism of such vagal efferent pathway(s) in an experimental model of ischemic heart disease. Design: Randomized experimental study. Setting: Research laboratory. Subjects: Adult Wistar rats of either sex. Interventions: After bilateral cervical vagotomy (with or without pretreatment with atropine), efferent vagal fibers were electrically stimulated in rats subjected to coronary artery occlusion (5 mins) followed by reperfusion (5 mins). Other rats (intact, vagotomized, or pretreated with atropine) were treated with nanomolar doses of melanocortin peptides. Measurements and Main Results: Electrical stimulation of efferent vagal fibers (5 V, 2 msecs,1-9 Hz, for the whole period of ischemia/reperfusion) strongly reduced the high incidence of severe arrhythmias and lethality, reduced the increase in free radical blood levels and left-ventricle histologic alterations, and augmented the extracellular signal-regulated kinase activation. Treatment with the melanocortin peptides adrenocorticotropin and gamma(2)-melanocyte-stimulating hormone (162 nmol/kg intravenously or 16.2 nmol/kg intracerebroventricularly, during coronary occlusion) produced the same protective effects of electrical stimulation and with the same muscarinic acetylcholine receptor-dependent mechanism, seemingly through brain activation (mediated by melanocortin MC3 receptors, as previously described) of such efferent vagal pathway. Conclusions: The present results give evidence for the identification of a protective, melanocortin-activated, efferent vagal cholinergic pathway, operative in conditions of myocardial ischemia/reperfusion. These data suggest that melanocortins and pertinent compounds able to activate such a pathway could provide the potential for development of a new class of drugs for a novel approach to management of ischemic heart disease.

2005 - Analisi comparativa della riparazione di difetti ossei con Fisiograft®. [Abstract in Rivista]
Ciacci, L.; Bellini, Pierantonio; Bertoldi, Carlo; Zaffe, Davide; Consolo, Ugo
abstract

Vedi allegato

2005 - Carcinoma e cheratosi orale [Monografia/Trattato scientifico]
A. R., Botticelli; G. C., Leghissa; M. C., Vitale; L., Botticelli; Zaffe, Davide
abstract

Monografia con lo scopo di formare studenti e laureati in Medicina e Chirurgia, Odontoiatria, specialisti di Odontostomatologia e di Anatomia patologica, all'attuazione di una diagnosi di lesione precancerosa e di una diagnosi precoce di carcinoma orale

2005 - Distrazione alveolare e stimolazione meccanica. [Abstract in Rivista]
Consolo, Ugo; Bertoldi, Carlo; Bellini, Pierantonio; Ciacci, L.; Zaffe, Davide
abstract

Vedi allegato

2005 - Grafting Autologous Cortical Bone in Regenerative Therapy: Preliminary Histological Evidence. [Articolo su rivista]
Consolo, Ugo; Ferri, V.; D’Avenia, F.; Zaffe, Davide
abstract

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2005 - Histological study on sinus lift grafting by Fisiograft and Bio-Oss [Articolo su rivista]
Zaffe, Davide; Leghissa, Gc; Pradelli, J.; Botticelli, Ar
abstract

The work aims to provide a histological investigation of Fisiograft(R) a PLA/PGA copolymer, used as filler for bone defects in humans. The study was performed on biopsies of sinus lifts where Bio-Oss(R) and Fisiograft(R) gel were applied as graft material. Bone regeneration was satisfactory in all sinus lifts, even when Fisiograft(R) was applied alone. Due to remarkable osteoclast activity, Bio-Oss(R) granules were cleared from the majority of biopsy cores. At histology, Fisiograft(R) gel appeared as globes enveloped by fibroblasts, displaying an epithelial-like cell appearance. Due to its solubility in solvents, undegraded Fisiograft(R) (recorded for 7 months or more) did not stain whereas degraded Fisiograft(R) stained positive. The loose connective tissue, that surrounded Fisiograft(R), and bone contained isolated mastocytes. Bone grew inside the loose connective and often reached the surface of Fisiograft(R) by intervening cells. The results seem to indicate that Fisiograft(R) may be considered both a polymer useful for fastening bone substitutes inside a defect and in addition a material capable of prompting bone regeneration, with or without the use of a bone substitute. In addition to space-former and space-maintainer functions, Fisiograft(R) shows potential bone stimulation function, which may be labelled as osteopromotive capability.

2005 - Innesti di corticale autologa da prelievi intraorali in terapia rigenerativa [Abstract in Rivista]
Consolo, Ugo; Ferri, V.; D’Avenia, F.; Zaffe, Davide; Bellini, Pierantonio
abstract

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2005 - Release of elements from retrieved maxillofacial plates and screws. [Articolo su rivista]
Bertoldi, Carlo; J. M., Pradelli; Consolo, Ugo; Zaffe, Davide
abstract

Vitallium appliances and surrounding tissues were investigated to evaluate the release and accumulation of elements.Four microplates, sixteen remaining screws and surrounding tissues were removed from three patients presenting inflammation 4 to 6 years after surgery for bone graft or fracture fixation and were submitted to SEM and X-ray microprobe analysis. Histology was performed on paraffin or PMMA sections of tissues.A continuous release of elements from metallic appliances into soft tissues was observed. Cobalt, chromium, and nickel were detected in soft and boney tissues in close proximity to the appliance. Aluminium, as a component of screw coatings, accumulated in soft tissues, and a remarkable amount of aluminium was detected in the dense lamella of lamellar bone.The results suggest that coatings containing aluminium should be avoided and the time these appliances are allowed to remain in patients should be shortened. Further studies on element release and the fate of aluminium in bone are warranted. IDS Number: 961PB PMID: 16167115

2005 - Some considerations on biomaterials and bone [Articolo su rivista]
Zaffe, Davide
abstract

Osteoinduction is a property not traditionally attributed to Calcium Phosphate ceramics. Histologic, SEM and X-ray microanalyses of a biopsy of pulmonary alveolar microlithiasis allow to discredit this opinion. Bone, even lamellar type, was ectopically formed on microliths undergoing osteoclastic erosion. The SEM and X-ray microanalyses of coral granules implanted in humans indicate an osteoconductive property for both Calcium and Phosphorus. Analysis of in vitro allows to propose an enhancement of the osteocapability of coral. Lamellar bone formation in the near absence of loads undermines the opinion which sees a correlation between lamellar bone and mechanical loads. Analysis of the bone surrounding an uncemented titanium hip prosthesis highlights that both remodeled and newly formed bone have lamellae oriented parallel to prosthesis surfaces, i.e. orthogonal to loads, as opposed to that of lamellar bone of osteons which are oriented parallel to loads. Analysis of longitudinal sections of cortical bone under polarized light points out that lamellae are displaced parallel to the cement line surface both in the conic end of osteons and in Volkman´s canals with thick wall, i.e. undergoing sloped load directions. In conclusion, there may be a relationship between lamellae formation and gravity.

2004 - Accumulation of aluminium in lamellar bone after implantation of titanium plates, Ti-6Al-4V screws, hydroxyapatite granules. [Articolo su rivista]
Zaffe, Davide; Bertoldi, Carlo; Consolo, Ugo
abstract

Titanium plates, Ti6Al4V screws and surrounding tissues, and biopsies of hydroxyapatite (Osprovit) grafts of maxillary sinus lifting were investigated to evaluate the release and accumulation of ions. Optical microscopy, SEM and X-ray microanalysis were carried out to evaluate the plates and screws removed from patients presenting inflammation and biopsies. Ions release from metallic appliances or leaching from granules towards soft tissues was observed. An accumulation of aluminium but not titanium was found in soft tissues. A peculiar accumulation of aluminium in the dense lamella of newly formed bone was recorded. The results seem to indicate that biological perturbations may be related to aluminium release from the tested biomaterials. The aluminium content of these biomaterials, its diffusion and accumulation are discussed. Further studies on ion release from biomaterials and aluminium fate in skeletal tissues are suggested. IDS Number: 808GS PMID: 15020159

2004 - Analisi degli effetti dello sbiancamento dentale con sorgenti a diodo [Articolo su rivista]
Bruzzesi, G.; P, DI MICHELE .; Grandini, S.; Guadagni, C.; Liviero, M.; Maggioni, M.; Zaffe, Davide
abstract

RIASSUNTO Scopo del lavoro. La richiesta di estetica odontoiatrica nei nostri studi è aumentata, negli ultimi anni, in modo esponenziale. Questo ha portato il lavoro del dentista a un cambiamento di rotta, con l’adozione di materiali e tecnologie decisamente innovativi, e a considerare l’eventualità di modificare in senso prettamente estetico l’aspetto del sorriso. L’industria ha messo prontamente a disposizione numerosi prodotti. I gel ossidanti attivati con luce laser a diodo fanno parte di questa categoria. In qualità di odontoiatri ci siamo chiesti come e quanto i trattamenti di sbiancamento laser assistiti potessero alterare l’equilibrio orale e, più specificamente, se il dente potesse subire un insulto chimico o termico in conseguenza di tali trattamenti. Materiali e metodi. Per la ricerca sono stati utilizzati14 elementi dentari umani, di cui 11 estratti e depulpati e 3 in cavità orale, perfettamente integri, successivamente estratti per motivi ortodontici. Risultati e conclusioni. I dati raccolti, per quanto esigui come quantità, possono suggerire alcune possibili deduzioni. Sarà necessario ampliare la casistica per ottenere un protocollo di ricerca valido e per fornire agli operatori dati certi per l’utilizzo in sicurezza di questa tecnica. ABSTRACT Aim of the work. Requests of dental aesthetic treatment are continuously increasing, thus changing many dental procedures with the use of new materials and techniques, but also the approach, in a more aesthetic view, to dentition. Diode laser activated peroxyde gels belong to this new category. The aim of this study is the analysis of the effects of laser assisted dental bleaching on dental surfaces. Materials and methods. Morphological changes of treated enamel and temperature variations during treatment were analysed. For the study 14 human teeth were used: 11 of them were extracted and deprived of the pulp and 3 were healthy teeth still in place, subsequently extracted for orthodontic reasons. Results and conclusions. Results are not quantitatively enough in order to fix an adequate research protocol and to assess reliable data for a safe use of this technique. Nonetheless some inferences are possible.

2004 - Endotendinous ossification and static osteogenesis: analogies and differences. [Abstract in Rivista]
Palazzini, S.; Palumbo, Carla; Ferretti, Marzia; Zaffe, Davide; Marotti, Gastone
abstract

In endotendinous ossification and in the early phase (SO) of intramembranous ossification the first trabecular framework fiorms in a different manner.

2004 - Laser and Paediatric Dentistry [Relazione in Atti di Convegno]
Vitale, M. C.; Caprioglio, C.; Scarpelli, F.; Botticelli, A. R.; Zaffe, Davide
abstract

Laser technology has different applications in dentistry, and, in particularly, in Paediatric Dentistry. Depending on wavelength of laser and physical properties of tissutal target, it could be possible obtain different results in three main dental fields : Diagnosis, Prevention and Operative Therapy. Conventional treatments can be replaced and better results obtained. Laser has proven to offer new treatment opportunities that were not available in the dental field in the past This article aims at illustrating clinical protocols and possible applications of different laser systems in paediatric dentistry.

2004 - L'innesto di osso corticale autologo in terapia rigenerativa: evidenze istologiche preliminari [Abstract in Rivista]
Consolo, Ugo; Ferri, V.; D'Avenia, F.; Zaffe, Davide
abstract

vedasi l'allegato

2004 - Morfologia del Fisiograft e Bio-Oss nel rialzo del seno mascellare. [Abstract in Rivista]
Leghissa, G. C.; Bertoldi, Carlo; Botticelli, A. R.; Zaffe, Davide
abstract

Il Fisiograft, copolimero PLA/PGA riassorbibile per difetti ossei, è stato utilizzato con Bio-Oss o da solo nel grande rialzo del seno mascellare. Sono stati scelti 15 pazienti tra i 30 ed i 68 anni, non fumatori e sistemicamente sani con atrofia mascellare posteriore di tipo 5 secondo la classificazione di Cawood & Howell. Dai 4 agli 8 mesi dall’intervento, nei siti di innesto, a livello dell’opercolo zigomatico, sono state compiute biopsie, che sono state valutate mediante colorazioni specifiche per i connettivi, per l’osso, per le mucoproteine ed i proteoglicani e con microradiografie. Il Bio-Oss ha dimostrato un livello di riassorbimento assai variabile ed incostante presentando quadri istologici in cui non veniva praticamente sostituito (a 8 mesi) accanto ad altri in cui era in atto una potente erosione osteoclastica. Nel compesso questo materiale presenta il comportamento tipicamente descritto nell’osteoconduzione. Il Fisiograft, invece, non viene praticamente mai a contatto con cellularità ossee specifiche anche se, al lato pratico, si dimostra in grado, anche quando usato da solo, di indurre tessuto osseo nei sinus lift. Il suo comportamento, quindi, non può essere definito osteoconduttivo ma neppure propriamente osteoinduttivo od osteogenetico; è sicuramente in grado, però, di indurre un’”osteopromozione” a livello delle sedi studiate.

2004 - Morphological, histochemical and immunocytochemical study of CO2 and Er:YAG laser effect on oral soft tissues. (Photomed. Laser Surg. formerly J. Clin. Laser Med. & Surg.) [Articolo su rivista]
Zaffe, Davide; Vitale, M. C; Martignone, A; Scarpelli, F; Botticelli, A. R.
abstract

Objective: The purpose of this study was to investigate the morphological, histochemical, and immunocytochemical changes of the oral mucosa after CO2 or Er:YAG laser irradiation. Background Data: There have been no comparative reports on CO2 and Er:YAG laser effects on human oral soft tissues. Materials and Methods: Tissue preservation was studied in 40 oral biopsies of young patients obtained by CO2 and Er:YAG laser surgery. Hematoxylin-eosin and Giemsa stains, PAS/diastase treatment, AE1 and AE2 cytokeratins, MiBI/Ki67, and bcl-2 immunoreactions were performed on the laser cut edges on formalin fixed, paraffin embedded biopsies. Results: CO2 laser biopsies show blisters, clefts and erosions of the epithelium. Intracellular edema and lengthened nuclei were also seen. The glycogen content results decreased in CO2 laser biopsies. Good expression for cytokeratins and cell-cycle proliferation markers were found in Er:YAG biopsies, on the contrary the apoptosis marker was better expressed in CO2 laser biopsies. Conclusion: The results suggest that Er:YAG laser may be routinely used in surgery, because of its minimal damage of the epithelial tissue, its low inflammatory reaction, its quicker healing process and its lower risk of scarring.

2004 - Prefabbricazione su misura di un innesto osseo neovascolarizzato con camera cilindrica in idrossiapatite: studio sperimentale [Articolo su rivista]
Tarallo, Luigi; Adani, R.; Marcoccio, Ignazio Mario; Celli, A.; Zaffe, Davide
abstract

Il concetto di prefabbricazione dei tessuti è divenuto in questi ultimi anni una realtà della chirurgia ricostruttiva. In un lavoro precedentemente svolto si è valutata la possibilitàdi creare un innesto osseo neovascolarizzato; il nuovo studio rappresenta l’evoluzione del precedente. Lo scopo è stato quello di creare un innesto osseo prefabbricato neovascolarizzato avvalendosi però, in questo caso di biomateriali come l’idrossiapatite per definirne forma e dimensioni prestabilite. Lo studio è stato condotto su conigli New Zealand suddivisi in tre gruppi. Nel gruppo A (5 animali) si è eseguito un prelievo di tessuto spongioso dalla cresta iliaca poi inserito in una camera di idrossiapatite di 15 mm di diametro richiudibile con due dischi, uno dei quali con un foro di 8 mm di diametro per consentire il passaggio del peduncolo vascolare. La spongiosa è stata miscelata con microparticelle di forma sferica di idrossiapatite. Il tutto è stato “neovascolarizzato” con l’arteria e la vena femorale superficiale delconiglio. Nel gruppo B (5 animali) sono state utilizzate, a differenza del precedente, solamente le microparticelle di idrossiapatite all’interno della camera. Infine nel gruppo C, di controllo, (3 animali) si è impiegata l’associazione di spongiosa e microparticelle di idrossiapatite senza però ricorrere all’impianto del peduncolovascolare. Le camere di idrossiapatite, avvolte da un foglietto di silicone sono state posizionate in una “tasca” tra i muscoli della faccia mediale della coscia di ciascun animale. Gli animali sono stati sacrificati a distanza di 3 mesi dall’intervento chirurgicoe i frammenti ossei sono stati fissati in paraformaldeide e poi in poli-metil-metacrilato a 4°C. Sezioni spesse e sottili di segmenti ossei sono state utilizzate per lo studio su microradiografie ed istologico al microscopio ottico, a luce ordinaria, polarizzata e fluorescente. Sono stati inoltre eseguiti studi e valutazioni al microscopio elettronico a scansione. Nel primo gruppo l’analisi delle sezioni istologiche ha evidenziato la neoformazione di un tessuto fibroso avvolgente sia l’idrossiapatite che l’osso, la presenza di osteociti vivi e di numerosi vasi neoformati. Nel secondo gruppol’idrossiapatite è risultata avvolta da un tessuto connettivo con presenza di vasi neoformati nei pressi del peduncolo vascolare. Il terzo gruppo è stato caratterizzato da una completa assenza di tessuti neoformati. In conclusione l’involucro utilizzato permette di conferire all’impianto una forma prestabilita; i risultati dimostrano una volta di più la capacità dell’impianto vascolare di indurre la neovascolarizzazione e confermano le caratteristiche di osteoconduzione dell’idrossiapatite. Le camere di idrossiapatite si dimostrano un valido supporto nel tentativo di conferire all’impiantouna forma “su misura”.

2004 - Preparazioni endocanalari con Er:YAG laser e fibroscopio. [Articolo su rivista]
Vitale, M. C; Scarpelli, F; Leghissa, G. C; Zaffe, Davide; Botticelli, A. R.
abstract

50 molari permanenti sono stati trattati endodonticamente in vivo sia con metodi convenzionali sia con il laser Er:YAG. Con un sistema ottico Flexiscope, è stata valutata l'efficacia nella rimozione dei detriti canalari prima e dopo i trattamenti. 40 denti permanenti, estratti a scopo ortodontico o per affezioni parodontali, sono stati trattati in vitro con la stessa tecnica e strumentazione e quindiesaminati al SEM. I risultati evidenziano una elevata detersione della superficie del canale pulpale con la asportazione di tutti i residui pulpari e dello smear layer dopo irradiazione con il laser.I risultati evidenziano che laser e verifica con sistema ottico possono essere particolarmente efficaci ed estremamente utilinell'applicazione clinica.

2004 - Sinus lift, commercia hydroxyapatites and uncommon bone. [Abstract in Rivista]
Zaffe, Davide; Bertoldi, Carlo; Consolo, Ugo
abstract

L’idrossiapatie (HA) è uno dei biomateriali alloplastici più estesamente impiegati in chirurgia rigenerativa orale. Lo studio è stato compiuto su 6 soggetti necessitanti di procedura chirurgica di sinus lift (rialzo maggiore di seno mascellare) per ptosi del pavimento sinusale ma diversamente in buona condizione di salute sistemica e locale. Al fine di stabilizzare il guadagno di spazio implantare ottenuto limitando il riassorbimento dell’osso autologo innestato, a quest’ultimo è stata aggiunta l’HA Osprovit in misura del 50% volumetrico. Il volume corrispondente al guadagno spaziale ottenuto con la procedura di sinu lift era, quindi, costituito nel 50% da osso autologo e nel restante 50% da Osprovit in tutti e 6 i casi clinici. In corrispondenza dell’allocazione impiantare, 6 mesi dopo l’innesto, sono state eseguiti prelievi bioptici in senso vestibolo-linguale in corrispondenza dell’opercolatura laterale. Si è notato un difetto di formazione ossea in rapporto ai granuli di HA con, viceversa una forte attività fosfatasica acida tartrato resistente (TRAP) indicativa di osteoclasia. Non si aveva, poi, nelle stesse zone esperessione della fosfatasi alcalina (TALP). Lontano dai granuli di Osprovit, invece, si riscontava osso neodeposto ed una buona attività TALP che è rapportabile all’azione osteoblastica. Il biomateriale, quindi, aveva successo nel non essere precocemente riassorbito ma in rapporto ad esso non si potevano dimostrare effetti osteogenetici né osteoconduttivi ma solo un dominante stato di osteoclasia. Successive valutazioni eseguite mediante microscopia elettronica a scansione (SEM) e sonda a raggi X per microanalisi (EDS system) rivelarono la presenza di alluminio nell’osso neoformato ed in particolare rapporto alle lamelle dense acellulari dell’osso lamellare.. Non ostante non fosse dichiarato nella composizione del prodotto, l’alluminio venne riscontrato nell’ Osprovit ed anche nel Biolox che è un prodotto nuovo che ha sostituito l’ Osprovit. L’utilizzo, quindi, di biomateriali al fine di diminuire la morbilità degli interventi e di contrarre il riassorbimento osseo è sicuramente una strategia clinica foriera di sviluppi. Non bisogna, però, dimenticare che le procedure di produzione di alcuni biomaterali possono comportare la formazione o la permanenza di alcuni costituenti che, pur garantendo migliori proprietà meccaniche al biomateriale stesso, potrebbero inficiarne gravemente gli effetti biologici.

2004 - Stimolazione meccanica nella distrazione alveolare mandibolare: valutazioni cliniche e morfofunzionali. [Articolo su rivista]
Consolo, Ugo; Bertoldi, Carlo; Zaffe, Davide
abstract

La distrazione osteogenetica alveolare (DOA), tradizionale (T) o meccanica-mente stimolata (S) è stata studiata in 16 soggetti altamente selezionati, sud- divisi in due gruppi. Valutazioni cliniche, radiografiche, densitometriche e istologiche su biopsie sono state effettuate a 6, 8 e 12 settimane dalla fine della distrazione. I risultati evidenziano una densità ossea densitometrica maggiore nei soggetti sottoposti a DOA-S. Negli stessi soggetti l’istologia dimostra la presenza di osso ordinato già dopo 6 settimane, disposizione architetturale orientata delle trabecole e presenza di osso lamellare in grande quantità a 8 e 12 settimane. In conclusione i risultati evidenziano una simili- tudine degli eventi osteogenetici, ma fortemente anticipati e meglio strutturati nei soggetti sottoposti a DOA-S rispetto a quelli sottoposti a DOA-T.

2004 - Studio comparativo di innesti autologhi da siti di prelievo diversi. [Abstract in Rivista]
Bertoldi, Carlo; Consolo, Ugo; Zaffe, Davide; Cossarizza, Andrea; Ceccherelli, G.
abstract

Scopo dello studio prospettico era la valutazione dello stato anatomo-funzionale e del comportamento degli innesti ossei prelevati da metafisi tibiale, cresta iliaca, sinfisi mentoniera e calvaria in rapporto alla tipologia degli interventi sui mascellari nell’ambito della chirurgia pre-protesica. Si sono scelte, a questo scopo, 2 tipologie di innesto: ad “onlay “ sul mascellare superiore e “particolato” per sinus lift. Al fine di inquadrare correttamente l’età ossea di riferimento per lo studio si è compiuta una valutazione preliminare su ossa di cadaveri utilizzando gli archivi del Dipartimento di Anatomia dell’Università di Modena e Reggio Emilia. Da tale studio si è evidenziata una grossa differenza nella strutturazione ossea tra l’individuo giovane e l’anziano (tranne che per la cresta iliaca in soggetti sani) per cui si è stabilito di restringere lo studio su soggetti sani in una fasca di età compresa tra i 20 ed i 65 anni. Valutazioni cliniche, radiologiche, istologiche e mediante tecniche biomolecolari (individuazione dei mRNA per le BMP-2 e BMP-7 mediante Real Time PCR) sono state compiute sugli innesti subito dopo il prelievo ed in fase di riapertura a scopo implantologico (circa 4 mesi dopo). Per quanto riguarda gli innesti ad “onlay” dal punto di vista istologico, istomorfometrico e biomolecolare pare regnare una situazione di rimodellamento osseo assai ridotta in tutti i casi e la produzione delle BMPs esaminate non pare essere significatamene differente tra i campioni neppure con stimolo mediante PRP. Dal punto di vista del Trabecular Bone Volume (TBV), invece, si distingue dagli altri l’innesto di origine mentoniera che appare significativamente più denso. I migliori risultati clinici che, secondo diversi studi, sono propri della calvaria in rapporto ad un suo migliore rimodellamento non possono essare ascritti a situazioni anatomiche di partenza né a differente attività di rimodellamento (quantitativamente parlando) o a una diversa situazione biomolecolare in rapporto alle BMP-2 & BMP-7.

2004 - Vetri bioattivi contenenti zinco: comportamento in viotro ed in vivo [Relazione in Atti di Convegno]
Lusvardi, Gigliola; Zaffe, Davide; Bertoldi, Carlo; Malavasi, Gianluca; Menabue, Ledi; Menziani, Maria Cristina; Pedone, Alfonso
abstract

Vedi allegato

2003 - Behavior of the bone-titanium interface after push-in testing: A morphological study [Articolo su rivista]
Zaffe, Davide; R. Rodriguez y., Baena; S., Rizzo; C., Brusotti; M., Soncini; R., Pietrabissa; Cavani, Francesco; V., Quaglini
abstract

Fourteen titanium dental implants (Tioblast(TM)) were implanted singly in the proximal tibia of New Zealand rabbits for 120 days. A bone defect was surgically produced and filled with Bio-Oss(R) around six of these implants. After the animals were sacrificed and their organs harvested, bone segments were fixed and methacrylate embedded after the push-in test had been performed. Microradiography was performed on longitudinal sections of the implants, whereas scanning electron microscope analysis was performed on the remaining embedded half-implants using secondary electrons only. The results showed that the implants were apically and coronally surrounded by bone, whether Bio-Oss(R) was used or not. Fractures were evident through the newly formed bone and between the pre-existing and newly formed bone. Some fracture lines propagated through the bone and stopped at the implant surface without continuing along the bone-titanium interface. Detachment between the implant and the bone occurred at the coronal extremity of the implants and along its cervical region. These results highlight the fact that the bone-titanium interface has a high resistance to loading. It exhibited greater resistance than the newly formed bone and seems to behave in a manner similar to the cement lines of osteons.

2003 - Biomatherials, ion release and bone behaviour. [Abstract in Atti di Convegno]
Zaffe, Davide; Bertoldi, Carlo; Consolo, Ugo
abstract

Il rilascio di costituenti dai materiali impiegati in rapporto con il tessuto osseo in ambito odontoiatrico e chirurgico maxillo-facciale è oggetto di studio sempre più approfondito con il progredire delle disponibilità tecnologiche nell’ambito dei biomateriali. Come si sa anche da precedenti studi degli autori, il meccanismo del rilascio di costituenti riveste una grande importanza nel definire le capacità integrative di un biomateriali. Gli autori intendono studiare il rilascio di costituenti da dispositivi in Titanio, Ti6Al4V, Vitallium e dall’Idrossiapatite. Valutazioni cliniche e radiologiche, ma anche con microscopia elettronica a scansione (SEM) sono state compiute. In rapporto al Vitallium ed alla lega Ti6Al4V si registravano i maggiori reperti clinici di flogosi. Tutti i costituenti, tuttavia, si dimostravano in grado di diffondere nell’ambito dell’organismo. Peculiari erano, a questo proposito, le mappe di diffusione del Titanio, limitatamente al tessuto fibroso, e dell’Alluminio, in rapporto alla lamella densa acellulare. Codice: IT\ICCU\USM\1644556

2003 - Effect of gamma-hydroxybutyrate in two rat models of focal cerebral damage [Articolo su rivista]
Ottani, Alessandra; Saltini, S.; Bartiromo, M.; Zaffe, Davide; Botticelli, A. R.; Ferrari, Anna; Bertolini, Alfio; Genedani, Susanna
abstract

Gamma-Hydroxybutyrate (GHB) and its lactone, gamma-butyrolactone (GBL) have been previously shown to produce a protective effect in animal models of cerebral ischaemia/hypoxia, as well as in human conditions of head injury-induced coma. The aim of the present research was to study the effect of GHB in experimental conditions of focal cerebral damage, either induced by ischaemia or excitotoxicity. Under general anaesthesia, rats were injected into the right striatum with either endothelin-1 (ET-1, 0.43 nmol) or kainic acid (7.5 nmol) in a volume of 1 mul. Sham-lesioned rats received 1 mul of the solvent. Both ET-1- and kainic acid-lesioned rats were randomly assigned to one of the following intraperitoneal (i.p.) treatments: (i) and (ii) GHB, 100 or 300 mg kg(-1) 2 h after the lesion, followed by 50 or 100 mg kg(-1), respectively, every 12 h; (iii) saline, 2 ml kg(-1), same schedule. Sham animals were treated with saline, 2 ml kg(-1), same schedule. Treatments lasted for 10 days. The higher dose of GHB produced a significant protection against the ET-1-induced impairments in sensory-motor orientation and coordinated limb use (evaluated 24 and 42 days after the lesion) and in place learning and memory (Morris test, performed 19 and 39 days after the lesion). The same dose regimen reduced the circling behaviour induced by apomorphine in kainate-lesioned rats (10 days after the lesion), and limited or prevented at all the histological damage produced either by ET-1 or by kainic acid (evaluated 43 or 10 days after the lesion, respectively). These results show that GHB limits both histological and functional consequences of a focal ischaemic or excitotoxic insult of the brain, in rats, even if the treatment is started 2 h after the lesion.

2003 - Effetto della rimozione precoce delle membrane per una rigenerazione ossea soddisfacente [Articolo su rivista]
Leghissa, G. C.; Botticelli, A. R.; Zaffe, Davide
abstract

L’effetto sulla rigenerazione ossea della rimozione precoce, dopo 4 settimane, di membrane in PTFE nella GBR (Bio-Oss® + Fisiograft®) di 8 pazienti, è stato valutato istomorfometricamente (TBV) su biopsie effettuate 4/5 mesi dopo l’inserzione degli impianti. L’istologia ha evidenziato una buona rigenerazione ossea senza segni infiammatori, L’ammontare medio di osso rigenerato era 81,3%, statisticamente non diverso (test di Mann-Whitney) da quello (P<0,24) rilevato in un precedente lavoro (con rimozione della membrana dopo 5 mesi), mentre il TBV era statisticamente inferiore (P<0,01). La rimozione precoce delle membrane sembra pertanto produrre soddisfacenti risultati nella riparazione di difetti ossei, anche se conferme su casistiche più ampie sono necessarie.

2003 - Element release from titanium devices used in oral and maxillofacial surgery [Articolo su rivista]
Zaffe, Davide; Bertoldi, Carlo; Consolo, Ugo
abstract

Optical microscopy, scanning electron microscopy and X-ray microanalysis (EDS system) were used on c.p. titanium devices (21 grids and 10 plates) removed from 28 patients without signs of inflammation 6-24 months after surgery. Plates, grids and surrounding tissue were investigated to evaluate the titanium release and accumulation. Titanium was only present in the interfacial bone, probably due to fretting, and in all fibrous tissue surrounding the devices. Titanium content followed a decreasing gradient extending from the device surface and was not detected at a distance greater than I mm. High titanium levels were found in blood cells in the connective tissue. In conclusion, titanium release from the devices stops only after bone is laid down on the titanium surfaces. Titanium release does not seem to interfere with the osteogenic process but perhaps may interact with it. (C) 2002 Elsevier Science Ltd. All rights reserved. IDS Number: 636KE PMID: 12504532

2003 - PLGA microspheres for oral osteopenia treatment: preliminary in vitro in vivo evaluation [Articolo su rivista]
Perugini, P; Genta, I; Conti, B; Modena, T; Cocchi, D; Zaffe, Davide; Pavanetto, E.
abstract

The aim of this work was to prepare and to evaluate in vitro/in vivo microspheres based on poly(D,L-lactide-co-glycolide) copolymers containing ipriflavone, for the local treatment of oral bone loss. The first objective was the preparation and in vitro characterization of ipriflavone loaded microspheres, by emulsion/solvent evaporation method. Process parameters such as drug:polymer weight ratio, and molecular weight of copolymers, were also investigated. The second objective was to elaborate a suitable animal model of mandibular osteoporosis, to evaluate the efficacy of these microparticulate drug delivery systems. In vivo experiments were carried out on female rats, in which oral osteopenia was induced by gonadectomy and molar avulsion. Morphometric analysis of mandibular segment were carried out to quantify the development of oral osteopenia and the efficacy of drug loaded microspheres. Results showed that ipriflavone loaded PLGA microspheres can be successfully obtained with good in vitro characteristics, utilizing the emulsification/solvent evaporation method. In vivo experiments revealed that local administration of microspheres produced only mild inflammation on the injection site. Morphometric analyses showed, at the level of the third molar, a slight increase in spongy and total bone mass on rat jaw treated with microspheres with respect to control. Control animals exhibited a scarce degree of osteopenia demonstrating that this animal model is not suitable for this purpose. (C) 2003 Elsevier Science B.V. All rights reserved.

2003 - Sinus lift, biomateriali e rilascio ionico. [Abstract in Rivista]
Bertoldi, Carlo; Bellini, Pierantonio; Consolo, Ugo; Zaffe, Davide
abstract

Al fine di limitare la subsidenza del rialzo nelle procedure di sinus lift, osservabile con l’innesto formato da solo osso autologo, idrossiapatite non riassorbibile (Osprovit®) è stata mescolata all’osso autologo in percentuale volumetrica del 50% in 6 pazienti. I deludenti risultati radiografici e clinico/terapeutici trovavano un riscontro nelle biopsie a 6 mesi che evidenziavano una riduzione del numero e della massa dei granuli di Osprovit® ed una forte riduzione ossea. A 3 mesi i granuli di idrossiapatite risultavano in via di disgregazione, circondati da cellule TRAP (fosfatasi acida tartrato-resistente) positive che li aggredivano e da un tessuto connettivo privo di attività TALP (fosfatasi alcalina). Attività osteogenetica elevata, valutata in termini di TALP, e neodeposizione ossea si riscontravano, invece, sull’osso innestato lontano dai granuli. Le analisi radiologiche densitometriche attuate sui siti di innesto davano risultati uniformi, compatibili con valori di osso mascellare, sui seni mascellari sottoposti a sinus lift con solo osso autologo ed utilizzati come controllo. I valori, invece, sui seni trattati con innesto autologo ed Osprovit® era diversificato. Si evidenziavano, infatti, due picchi gaussiani, uno attestato in un intorno di 1700 HU, congruente per l’idrossiapatite e l’altro mediamente inferiore a quello riscontrato nei seni con solo innesto osseo. Queste evidenze, nel complesso, rendono ragione di uno stato di sofferenza dell’innesto nei siti trattati anche con l’idrossiapate ma non ne chiariscono, tuttavia, l’etiopatogenesi. Indagini successive al SEM (microscopio elettronico a scansione) e con microsonda a raggi X evidenziano nel connettivo dei seni trattati anche con idrossiapatite la presenza di calcio, fosforo ma anche alluminio. Questo ultimo elemento è, in particolare, accumulato nel tessuto circostante i granuli. L’alluminio è, ancora, presente nell’osso neoformato, posto anche a distanza dai granuli,, con localizzazioni peculiari in rapporto alle lamelle dense acellulari. Tale elemento risulta nella composizione dell’Osprovit®, ma anche dell’attuale prodotto commerciale Biolox Osprovit® che lo ha sostituito. I risultati, nell’avvalorare un possibile rapporto tra la natura biochimica del biomateriale e i risultati clinici negativi ottenuti, ingenerano, inoltre, perplessità in considerazione della pericolosità dell’alluminio, in particolare sul sistema nervoso

2002 - Efficacia del PRP nella riparazione dei difetti ossei. [Abstract in Rivista]
Consolo, Ugo; Bertoldi, Carlo; Ceccherelli, G.; Cossarizza, Andrea; Zaffe, Davide
abstract

L’attivita del platelet-rich plasma (PRP) sulla rigenerazione ossea è stata valutata su colture cellulari “in vitro” ed “in vivo”. Una volta compiuto un espianto osseo, parte di questo materiale, con il preventivo consenso informato del paziente, era posto in coltura cellulare con 2 modalità: coltivando l’intero trabecolato, senza estrarne la cellularità e coltivando la cellularità, estratta con metodi fisici dall’osso raccolto. In entrambi i casi si sviluppavano colture in terreni arricchiti o meno con PRP. Su tali espianti si eseguono valutazioni morfologiche, micromorfologiche, antigeniche, per mezzo della citofluorimetria, e biomolecolari, andando ad analizzare la produzione di mRNA per le BMP2 e 7 tramite la REAL TIME PCR. In vivo, il PRP era appilicato su una popolazione di 30 difetti cistici odontogeni apicali (resistenti alla terapia endodontica e di diametro * di 2cm) e di 12 siti atrofici mascellari bilaterali (grado IV-VI secondo Cawood e Howell) sovrapponibili. In alcuni difetti cistici il PRP è testato da solo come gel di riempimento, , addizionato ad osso autologo in altri difetti cistici ed in uno dei due seni mascellari. Tali interventi vengono confrontati tra loro ed in rapporto al solo osso autologo, rispettivamente, impiegato come riempitivo in altri difetti cistici e nei sinus lift nel seno mascellare controlaterale a quello in cui l’osso era utilizzato con PRP. I confronti, in questo campo, avvengono su base clinica, radiologica (completa di analisi densitometrica) ed istologica Le colture presentano risultati morfologici contrastanti nei due diversi casi in cui nelle fiasche si coltivi l’intero trabecolato o le sole cellule estratte dall’espianto osseo. Nel primo caso il PRP parrebbe favorire la formazione di tessuto calcifico; non così nel secondo caso in cui le colture hanno un aspetto del tutto sovrapponibile. I risultari micromorfologici ed antigenici citofluorimentrici parrebbero indicare la presenza di una popolazione cellulare attivata pro-osteogenetica nelle colture trattate con PRP. I risultati derivanti dalla REAL TIME PCR rilevano capacità di induzione delle BMPs studiate, da parte del PRP, presente ma non eclatante. I risultati “in vivo” sembrerebbero confermare la capacità del PRP di causare una accelerazione dei processi di guarigione e di osteogenesi nel caso in cui l’ambiente sia “condizionato” dalla presenza di tessuto osseo. I limiti temporali, tuttavia parrebbero essere molto importanti e l’azione del PRP sembrerebbe vantaggiosa fino a non oltre i 4/5 mesi dall’intervento di innesto. Tali risultati, che potrebbero essere contigui a quelli ottenuti “in vitro”, necessitano tuttavia di ulteriori studi e conferme.

2002 - Experimental procedure for the evaluation of the mechanical properties of the bone surrounding dental implants [Articolo su rivista]
M., Soncini; Rr, Baena; R., Pietrabissa; V., Quaglini; S., Rizzo; Zaffe, Davide
abstract

The mechanical stability of the fixture in bone is one of the most important factors for the long-term reliability of dental implants. This paper focuses on an experimental procedure to evaluate the mechanical properties of the bone surrounding dental implants. The procedure is based on a surgical animal model followed by mechanical tests. The experimental mechanical testing has been used for preliminary investigations on the role played by different parameters such as the healing time and the surgical technique (standard or with regenerative material). The procedure has been evaluated in some preliminary tests on a few specimens. Microradiographic analyses have been performed on the bone surrounding the implants in order to give an interpretation of the bone properties on the basis of the bone morphology and to distinguish the newly formed bone from the pre-existing bone. The preliminary results relevant to 10 threaded titanium implants are presented and discussed. Our findings show that the mechanical properties of the bone surrounding the implant improve with the increase in the healing time from 24 to 45 days. The ultimate loads recorded during mechanical tests arise from 395 N to 2665 N in case of coronal defects filled with bone regenerative and from 2200 N to 5700 N in case of standard technique. (C) 2001 Elsevier Science Ltd. All rights reserved.

2002 - In vivo effects of low-frequency low energy pulsing electromagnetic fields (PEMFs) on gene expression during the inflammation phase of bone repair [Articolo su rivista]
Zucchini, P; Zaffe, Davide; Botti, P; Grande, Alexis; Cavani, Francesco; Cadossi, M; Ferrari, Sergio; Cadossi, Ruggero; Fini, M; Canè, Valerio
abstract

It has been widely demonstrated that pulsed low-frequency electromagnetic fields (PEMFs) positively affect bone repair. The aim of this study is to highlight if PEMFs influence cell metabolic activity during the replacement of the blood clot with granulation tissue in the inflammation phase of bone repair. Four equal transcortical holes were made, at the same diaphyseal level, in both metacarpals (McIII) of five mate adult horses. The left McIII were exposed to PEMFs 24 hr/day; the right untreated McIII were used as controls. Eight days after surgery, the horses were sacrificed. We investigated the effect of PEMFs on 1) histological aspects of the lesion, 2) histochemical detection of the bone marker alkaline phosphatase, and 3) molecular markers as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and transforming growth factor-beta1 (TGF-beta) by reverse transcriptase-polymerase chain reaction amplification (RT-PCR). The histological analysis indicates that the blood clot, in both PEMF treated and control holes, is being replaced by granulation tissue extending from the endosteal towards the periosteal side of the lesion. TALP positive areas do not exactly correspond to the areas where fibroblasts are present, these being wider than the former. The study of the expression of the mRNA of TGF-beta1 shows no differences between treated holes and control ones. The expression of TNF-alpha and IL-6 however, is not univocal, being sometimes more expressed, sometimes less in treated or control holes. These data show that PEMFs exposure affects the expression of inflammatory cytokines (TNF-alpha and IL-6) during the very early stages of bone repair. On the contrary TFG beta expression and histological findings are not modified by PEMF exposure at least in this experimental condition.

2002 - Morphofunctional and clinical study on mandibular alveolar distraction osteogenesis [Articolo su rivista]
Zaffe, Davide; Bertoldi, Carlo; Palumbo, Carla; Consolo, Ugo
abstract

Alveolar Distraction Osteogenesis (ADO) is a process which forms new alveolar bone to correct alveolar deformities in ridge height and width. This work aims (a) to verify the predictability of the augmentation of height of atrophic alveolar ridges using an extra-alveolar distraction device and (b) to study the bone processes in order to optimize implantoprosthetic rehabilitation. ADO was performed on 10 patients with ridge deformities to obtain the required ridge augmentation. Clinical and radiological (OPT and CT with densitometric assay) evaluations were carried out during the following 12 weeks, before implant insertion. Biopsies at 40, 60 and 88 days were studied after general, specific and histochemical staining of slides; microradiographs were analyzed to evaluate the Trabecular Bone Volume. Forty days after the end of distraction, soft callus indicated the start of ossification. Sixty days after the end of distraction, the soft callus was largely converted into a network of trabecular woven bone; osteogenic activity was high and TBV was about 50%. Eighty-eight days after the end of distraction, the amount of bone appeared reduced, with a more ordered structure; bone formation activity and TBV also diminished, whereas osteoclast erosion was active. The densitometric assay shows values increasing from the end of distraction, particularly after implant insertion. Histological results show a regression in bone deposition processes 88 days after the end of distraction culminating in a virtual steady-state after a certain time. The results suggest that early implant insertion may be desirable to avoid bone loss due to mechanical unloading. IDS Number: 625CN PMID: 12453134

2001 - Alveolar distraction osteogenesis: is the process improvable? [Relazione in Atti di Convegno]
Consolo, Ugo; Bertoldi, Carlo; Bellini, Pierantonio; Zaffe, Davide
abstract

Bone processes of Alveolar Distraction Osteogenesis (ADO) were studied to optimize the implanto-prosthetic rehabilitation. ADO was applied on 11 patients with ridge deformities. Clinical and radiological evaluations, and morphological (histology, histochemistry, microradiography) studies were performed during the following 12 weeks. Ossification starts at 40 days after the end of distraction. Sixty days after the end of distraction, soft callus was widely converted into a network of trabecular woven bone and high osteogenic activity (TBV about 50%). Osteoclast resorption reduces the bone amount (TBV about 37%) though there was a more ordered bone structure 88 days. Densitometric assay shows increasing values since the end of the distraction. The results suggest the possibility of avoiding bone loss due to mechanical unloading through an early implant insertion ISI WOS:000172402500019 IDS Number: BT24C

2001 - An HA-chamber for biomaterial evaluations: first results [Relazione in Atti di Convegno]
Zaffe, Davide; R., Adani; A., Ravaglioli; A., Kraiewski; M., Mazzocchi
abstract

An hydroxyapatite (HA) cylindrical chamber, containing a vessel pedicle surrounded by autologous bone and/or HA spherules, was placed in each medial right thigh of 15 New Zealand male rabbits for 3 months. Results show the displacement of chambers from the original position, several new formed blood vessels, erosion of the bone graft, with living osteocytes inside, and a little osteoclast aggression of HA spherules. New bone has formed both on bone graft and HA spherules, whereas no bone formation was detected when HA spherules were the only graft used. In conclusion, the results confirm the osteoconductive features of the used HA, highlight the effectiveness of the HA chamber and some critical aspects which can be improved to obtain the best effects.

2001 - Cessione di elementi da dispositivi per fissazione interna rigida in vitallium. [Articolo su rivista]
Zaffe, Davide; Bertoldi, Carlo; Consolo, Ugo
abstract

Gli autori analizzano il comportamento di diversi dispositivi in vitallim utilizzati, prevalentemente in passato, in ambito oro-maxillo-facciale per esigenze di stabilizzazione rigida dei frammenti ossei. Ad un soggetto, latore di una forma di grado elevato di flogosi locale in rapporto al mezzo osteosintetico, tali dispositivi sono stati necessariamente espiantati ed analizzati assieme ai tessuti circostanti. L’analisi, condotta tramite le usuali tecniche istologiche ma anche per mezzo di scansioni elettroniche e microsonda a raggi X, ha inequivocabilmente dimostrato la diffusione dai mezzi osteosintetici di frazioni di cromo, cobalto, wolframio e nickel. I rapporti tra tale diffusione dei suddetti costituenti metallici, il corrispondente loro accumulo ionico ed la contemporanea presenza di flogosi in rapporto a materiali noti per avere la capacità di generare risposte patologiche da parte dell’organismo, suggeriscono un maggior controllo nell’impiego di materiali meccanicamente dotati da qualità elevate ma perfettamente in grado, dal punto di vista biologico, di generare patologia.

2001 - Combination of an optic system and Er:YAG laser in root canal preparation: study in vivo and in vitro [Relazione in Atti di Convegno]
Vitale, M. C.; Botticelli, A. R.; Zaffe, Davide; Cisternino, A.; Scarpelli, F.
abstract

The effect of Er:YAG laser in debris removing after conventional root preparation was tested by optical system in vivo and scanning electron microscope in vitro.The root canal of fifty permanent molars was cleaned in vivo and Er:yag laser treated. Flexiscope system was used to evaluate the efficacy of laser cleansing at the different stages of endodontic therapy. Forty permanent teeth, extracted for orthodontic or periodontal purposes, were treated in vitro using the same technique and instruments. The in vitro treated teeth were also examined under the SEM.The results of our investigation show an effective improvement of the cleansing of the endodontic surface from pulpal remaining and a smear layer after laser irradiation in vivo and in vitro. The use of Er:YAG laser in organic debris removing and the consequent optical system analysis of the quality of root preparation in vivo seem to be a reliable technique particularly useful in clinical application.

2001 - CO2-laser biopsies of oral mucosa: an immunocytological and histological comparative study [Relazione in Atti di Convegno]
Vitale, M. C.; Botticelli, A. R.; Zaffe, Davide; Martignone, A.; Cisternino, A.; Vezzoni, F.; Scarpelli, F.
abstract

The relationship between bioptic technique and tissue preservation has been studied in 18 oral biopsies of young patients obtained by electrosurgery or CO2 laser surgery. Biopsies were formalin fixed, paraffin embedded and histologically, histochemically and immunocytochemically (SBS-DAB method) treated. All the biopsies show inflammatory cell infiltration, epithelial spongiosis, trichocariosis, suprabasal small blisters, and epithelial clefts with lamina detaching from the corium. Histochemistry shows both the presence of edema and acid mucopolysaccharides inside the corium, and variable glycogen content in epithelial cells. Trichocariotic cells show a positive MiB1/Ki67 expression, when they are present. Nevertheless, laser biopsies show a lower amount of basophilic fibrous tissue and of bcl2 bodies detection, connected with a higher amount of glycogen, Cytokeratin and MiB1/Ki67 expression in epithelial cells, compared to bovie biopsies. The results show a higher degree of damages in particular at the epithelial level, in electrosurgery biopsies rather than laser biopsies. The best epithelial and corium preservation showed by laser biopsies suggest a chance of reversible condition, which can lead to a complete recovery due to its higher capability of restoring tissues.

2001 - Dispersione nei tessuti limitrofi di elementi metallici provenienti da sistemi di fissazione rigida. [Relazione in Atti di Convegno]
Consolo, Ugo; Bellini, Pierantonio; Bertoldi, Carlo; Zaffe, Davide
abstract

La diffusione di costituenti metallici corpuscolari o ionici da mezzi protesici o meno innestati in ambito biologico è accertato che possa condurre ad importanti effetti collaterali che si sviluppano in fenomeni flogistici, allergici o in altre patologie sistemiche anche croniche (es.: intossicazioni, patologie da accumulo, forme parkinsoniane, demenze pre-senili). Scopo della presente ricerca è di rilevare la diffusione di costituenti metallici da viti e placche impiegate per fissazione interna rigida rapportandola ad un indice di flogosi locale. La ricerca è stata condotta su 18 pazienti mediante monitorizzazioni cliniche, radiologiche, istologiche e di scansione elettronica con sonda per microanalisi. In questo studio è sempre stato documentato un certo grado di “aggressione” dei dispositivi metallici da parte dell’organismo. Nei soggetti con gradi più elevati di flogosi, si evidenziava una maggior dispersione tissutale di costituenti. In gran parte questi ultimi casi erano in rapporto a placche in vitallium piuttosto che di titanio. Anche quest’ultimo elemento, tuttavia, si dimostra in grado di diffondere nei tessuti. Non ostante al riguardo del titanio non siano, per ora, documentabili effetti flogistici o tossici sovrapponibili ad altri costituenti metallici (es.: nickel o alluminio), occorre dire che molti studi circostanziali non sono stati ancora condotti sull’argomento. Saranno, perciò, opportune altre ricerche inerenti sia gli schemi di dispersione tissutale dei microcostituenti che la loro eventuale pericolosità.

2001 - Elementi metallici nei tessuti circondanti dispositivi per fissazione interna rigida FIR [Articolo su rivista]
Bertoldi, Carlo; Consolo, Ugo; Bellini, Pierantonio; Zaffe, Davide
abstract

Obiettivo. Placche e altri dispositivi in lega metallica sono stati introdotti per ottenere la stabilizzazione di frammenti ossei fratturati. Gli elementi che costituiscono le leghe sono stati riscontrati soprattutto in diversi organi, ma anche localmente nei tessuti circondanti i dispositivi. Scopo del presente studio è l’analisi dei tessuti circondanti dispositivi per FIR al fine di evidenziare la diffusione di elementi, analizzando la morfologia delle particelle liberate e studiando il comportamento dei tessuti.Metodi.Il materiale bioptico fu ottenuto da 18 pazienti (20÷76 anni di età), portatori di placche, viti e griglie per FIR da 4 mesi a 9 anni. I pazienti furono suddivisi in 5 gruppi in rapporto al grado flogistico locale. Microscopio ottico, elettronico a scansione e microanalisi a raggi X (EDS system) furono utilizzati nello studio morfologico e nell’identificazione delle particelle metalliche e degli elementi.Risultati. Particelle metalliche o elementi mobilizzati da placche, viti o griglie possono generare diffusione tissutale e uptake cellulare. Non solo Cromo, Ferro o Alluminio ma anche Titanio può facilmente essere rilasciato dai dispositivi e accumularsi nei tessuti. La diffusione del Titanio è particolarmente evidenziabile nel tessuto fibroso circondante i dispositivi per FIR. L’Alluminio non solo mostra una maggiore persistenza nel tessuto fibroso, ma esibisce un particolare comportamento di accumulo nell’osso lamellare. Conclusioni. Il grado flogistico locale sembra essere strettamente correlato alla metallosi. Non solo Cromo, Ferro, Alluminio ma anche Titanio, anche se con un diverso grado, possono originare effetti flogistici. La metallosi e la flogosi danno origine probabilmente a un processo a cascata nel quale possono essere sia causa che effetto allo stesso tempo. Il deciso rilascio di Titanio, che normalmente non produce effetti clinici flogistici come per esempio quelli prodotti dall’Alluminio, necessiterebbe ulteriori approfondimenti sui suoi effetti sulle cellule. PMID: 11420563

2001 - Melanocortin peptides prevent the ischemia and reperfusion-induced myocardial damage. [Abstract in Rivista]
Cainazzo, Maria Michela; Bazzani, Carla; Botticelli, A.; Zaffe, Davide; Tomasi, Aldo; Bini, Anna; Ferrazza, G.; Mioni, Chiara; Bertolini, Alfio; Guarini, Salvatore
abstract

Melanocortin peptides prevent the ischemia and reperfusion-induced myocardial damage.

2001 - Osteocyte-osteoclast morphological relationships and the putative role of osteocyte in bone remodeling [Articolo su rivista]
Palumbo, Carla; Ferretti, Marzia; A., Ardizzoni; Zaffe, Davide; Marotti, Gastone
abstract

An osteocyte lacunae differential count under the light microscope (LM) (1-lacunae with live osteocytes, 2-empty lacunae and lacunae with degenerating osteocytes) was carried out outside the reversal lines of osteonic lamellar bone from various mammals and man to evaluate the possibility of osteocyte survival where osteoclast resorption had occurred. The polarized light microscope (PLM) was used to establish the curvature of bony lamellae outside the convexity of reversal lines: concave lamellae indicate osteocytes reabsorbed on their vascular side where they radiate long vascular dendrites; convex lamellae indicate bone resorption on the osteocyte mineral side, radiating short dendrites. In all samples it was found that: a) about 60% of osteocytes outside the reversal lines were live; b) the percentage of alive osteocytes close to reversal lines is higher when they are attacked on their mineral side. The present data support our view that surviving osteocytes, particularly those attacked from their mineral side, might intervene in the final phase of bone resorption (osteoclast inhibition?). The fact that under the transmission electron microscope (TEM) intercellular contacts were never observed between osteocytes and osteoclasts indicates that if a modulation should occur between these two cellular types it could take place by a paracrine route only. The putative role of the cells of the osteogenic system, particularly osteocytes, in the bone remodeling cycle is also discussed.

2001 - Osteocyte-osteoclast morphological relationships and the putative role of osteocytes in bone remodeling. [Articolo su rivista]
Palumbo, Carla; Ferretti, Marzia; Ardizzoni, Andrea; Zaffe, Davide; Marotti, Gastone
abstract

An osteocyte lacunae differential count under the light microscope (LM) (1-lacunae with live osteocytes, 2-empty lacunae and lacunae with degenerating osteocytes) was carried out outside the reversal lines of osteonic lamellar bone from various mammals and man to evaluate the possibility of osteocyte survival where osteoclast resorption had occurred. The polarized light microscope (PLM) was used to establish the curvature of bony lamellae outside the convexity of reversal lines: concave lamellae indicate osteocytes reabsorbed on their vascular side where they radiate long vascular dendrites; convex lamellae indicate bone resorption on the osteocyte mineral side, radiating short dendrites. In all samples it was found that: a) about 60\% of osteocytes outside the reversal lines were live; b) the percentage of alive osteocytes close to reversal lines is higher when they are attacked on their mineral side. The present data support our view that surviving osteocytes, particularly those attacked from their mineral side, might intervene in the final phase of bone resorption (osteoclast inhibition?). The fact that under the transmission electron microscope (TEM) intercellular contacts were never observed between osteocytes and osteoclasts indicates that if a modulation should occur between these two cellular types it could take place by a paracrine route only. The putative role of the cells of the osteogenic system, particularly osteocytes, in the bone remodeling cycle is also discussed.

2001 - Platelet-rich plasma in sinus lifting and bone defects. [Abstract in Rivista]
Consolo, Ugo; Bodin, C.; Bertoldi, Carlo; Pregarz, M.; Zaffe, Davide; Sgroi, S.
abstract

Vedi allegato (in inglese) Abstract in Italiano: Gli autori vogliono studiare le capacità osteogenetiche mediate dal platelet-rich plasma (PRP) in rapporto a modelli di riabilitazione protesica su impianti. Vengono studiati i comportamenti inerenti la rigenerazione ossea in difetti intraossei ed, inoltre, sono studiati 8 pazienti sottoposti a procedura bilaterale di sinus lift, accuratamente studiati per condizioni generali e per presentare, bilateralmente, lo stesso grado di atrofia in rapporto alla ptosi sinusale. I risultati delle valutazioni cliniche, radiologiche ed istologiche consentono di ritenere che l’utilizzo del PRP, per tempistiche precise dall’intervento, può indurre benefici in termini di volumetria e di “vitalità” ossea.

2001 - Protective effect of melanocortin peptides in rat myocardial ischemia [Articolo su rivista]
Bazzani, Carla; Guarini, Salvatore; Botticelli, A. R.; Zaffe, Davide; Tomasi, Aldo; Bini, Anna; Cainazzo, M. M.; Ferrazza, G.; Mioni, C.; Bertolini, Alfio
abstract

The influence of the melanocortin peptide ACTH-(1-24) (adrenocorticotropin) on the consequences of short-term coronary ischemia (5 min) followed by reperfusion, and the effect of the long-acting melanocortin [Nle(4),D-Phe(7)]alpha -melanocyte-stimulating hormone (NDP-MSH) on the damage induced by a permanent coronary occlusion, were investigated in anesthetized rats. Ischemia was produced by ligature of the left anterior descending coronary artery. Reperfusion-induced arrhythmias [ventricular tachycardia (VT), ventricular fibrillation (VF)] and survival rate within the 5 min following reperfusion, blood levels of free radicals detected 2 min after reperfusion by electron spin resonance spectrometry, and amount of healthy myocardial tissue, measured 72 h after permanent coronary occlusion on immunohistologically stained serial sections, were evaluated. Postischemic reperfusion induced VT in all saline-treated rats, and VF and death in a high percentage of animals (87%). In rats treated i.v. (2.5 min after coronary occlusion) with ACTH-(1-24) (0.16-0.48 mg/kg) there was a significantly dose-dependent reduction in the incidence of arrhythmias and lethality. Ischemia/reperfusion caused a large increase in free radical blood levels; treatment with ACTH-(1-24) (0.48 mg/kg i.v.) almost completely prevented this increase. In rats subjected to permanent coronary occlusion, the amount of healthy myocardial tissue was much reduced in saline-treated rats, while in rats treated s.c. with NDP-MSH (0.27 mg/kg every 12 h) it was significantly higher. The present data demonstrate, for the first time, an unforeseen property of melanocortin peptides, i.e., their ability to significantly reduce both heart ischemia/reperfusion injury and size of the ischemic area induced by permanent coronary occlusion.

2001 - PROTESIS IMPLANTOSOPORTADA. Báses Biológicas, biomecánica y aplicaciones clínicas [Monografia/Trattato scientifico]
A. E., Bianchi; F., Sanfilippo; Zaffe, Davide
abstract

CONTENIDO * Bases biológicas - Histofisiopatología del tejido óseo. Histogénesis causal del tejido óseo. Formación ósea intramembranosa. Formación ósea endocondrial. Crecimiento de la longitud de los huesos. Crecimiento diametral de los huesos. Reorganización interna del hueso. Niveles organizativos del tejido óseo. Matriz ósea. Matriz inorgánica. Matriz orgánica: la componente fibrilar. Matriz orgánica: la componente no fibrilar. Células óseas * Aspectos biomecánicos - Aspectos morfoestructurales del hueso peri-implantar. Los biomateriales. Interfaz hueso-titanio. Toma de muestras biópticas humanas. Organización de la arquitectura y del tejido óseo peri-implantar. Morfología de la superficie ósea en la interfaz. Competencia biomecánica del sustrato de sostén y estabilidad tisular. Propagación de las cargas del implante al sustrato. Adaptación morfoestructural en el caso de tipos morfológicos implantes peculiares * Aplicaciones clínicas - Cirugía implantológica especial. Evolución de los huesos maxilares después del edentulismo. Región interforamen. Región periforamen. Región posterior. Región frontal. Osteoporosis * Tratamiento protésico con implantes. Prótesis provisional: aspectos biomecánicos. Prótesis provisional: funcionalidad gradual. Prótesis provisional: aspectos estéticos. Sistema biomecánico y carga funcional. * Regeneración ósea guiada. Promoción ósea. Clasificación de los defectos óseos peri-implantares. Membranas no reabsorbibles. Membranas reabsorbibles. Líneas guía con membrana en e-PTFE. * Injertos óseos autólogos. Integración al injerto. Indicación de los injertos óseos. Osteoconducción. Osteoconducción sin utilización de membranas. Osteoconducción con membranas reabsorbibles. * Tratamiento integrado ortodóntico implantar. Anclaje ortodóntico. Consideraciones sobre el plan de tratamiento integrado otodoncia-implante. Agenesias. Agenesias dentarias múltiples. * Resultados de labio-palato-esquisis. Clasificación de los resultados de LPS. Ubicación inadecuada de los implantes en LPS. Injertos de hueso autólogo en los casos de LPS. * Complicaciones. Complicaciones quirúrgicas inmediatas. Complicaciones post-quirúrgicas precoces.Complicaciones post-quirúrgicas tardías. Complicaciones protésicas * Alteraciones patológicas de los tejidos peri-implantares. Teoría plaquetaria. Teoría sobre carga. Diagnóstico de las alteraciones patológicas de los tejidos peri-implantares.La presente obra se ha impuesto el objetivo de integrar la separación, a menudo existente, entre la pura investigación de histofisiopatología del tejido óseo y la realidad clínica de la cirugía reconstructiva e implantar. Con el fin de hacer más simple el recorrido didáctico, el desarrollo ha previsto una amplia utilización de esquemas y de imágenes, macrofotografías y radiografías, imágenes en el microscopio óptico con análisis de las preparaciones con múltiples metodologías comparables, microrradiografías, observaciones estructurales con el microscopio electrónico de barrido y ultraestructurales en microscopía electrónica de trasmisión; esto ha permitido documentar, en la forma más exhaustiva posible, no sólo la descripción de células y tejidos, sino también, las condiciones fisiológicas y patológicas del substrato mineralizado que forma parte del sostén de los implantes.La difusión de la metodología y su posterior aplicación rutinaria, han conducido a un afinamiento de las técnicas y al perfeccionamiento de los protocolos, que en los últimos años han determinado la transformación del abordaje implantológico.DE INTERÉS PARA: * Cirugía y Prótesis Reconstructiva Implantar * Prótesis Fijas y Removibles

2001 - PRP nel sinus lifting e nel trattamento dei difetti cistici. [Abstract in Atti di Convegno]
Consolo, Ugo; Bertoldi, Carlo; Ceccherelli, G.; Cossarizza, Andrea; Zaffe, Davide
abstract

Gli autori hanno studiato una popolazione di pazienti che sarebbero stati sottoposti a procedura di enucleazione cistica (cisti odontogene di tipo flogistico apicale, con diametro *2cm e resistenti alla sola terapia endodontica) ed una popolazione selezionata di soggetti che avrebbero dovuto sottoporsi a sinus lift bilaterale per sanare situazioni bilateralmente sovrapponibili di atrofia di 4-6 grado secondo Cawood e Howell. Una tipologia di sperimentazione avveniva in un ambito favorevole alla genesi ossea (lesione cistica) mentre l’altra tipologia di intervento veniva eseguita in una posizione sfavorevole. Nello stesso tempo la bilateralità dell’intervento di quest’ultima serie (sinus lift) dava la possibilità di confrontare sullo stesso soggetto, quindi con una forte epicriticità di osservazione, le differenze indotte dal Platelet-rich Plasma (PRP). Infatti la procedura di sinus lift sarebbe stata eseguita da un lato con solo innesto osseo autologo mentre, nel controlaterale, l’innesto osseo sarebbe stato addizionato con PRP. Scopo del presente lavoro era analizzare la capacità del PRP di indurre tessuto osseo e di stabilizzarlo in sede. I nostri risultati, sebbene preliminari, sembrerebbero indicare un’accelerazione, indotta dal PRP, dei processi di rigenerazione tissutale. Tale costituente sarebbe in grado di agire in modo generalizzato su tutti i tessuti di tipo connettivale, almeno, stimolandone la crescita. Codice: IT\ICCU\BVE\0248681

2001 - Sinus lifting and cystic bone defects treated with platelet-rich plasma. [Abstract in Rivista]
Consolo, Ugo; Bertoldi, Carlo; Zaffe, Davide; Cossarizza, Andrea; Ceccherelli, G.; Bellini, Pierantonio
abstract

Vedi allegato (in Inglese) Riassunto italiano: Da una popolazione di pazienti che si sottopone a procedure di innesto osseo, previo consenso informato, vengono prelevati alcuni cc aggiuntivi di osso. Tali campioni vengono ad essere coltivati in vitro in presenza o, rispettivamente, in assenza di Platelet-rich Plasma. La cellularità ossea, tuttavia, non veniva separata dalle rispettive trabecole con cui, invece, veniva incubata. Le diverse colture, una volta giunte a confluenza, vengono ad essere analizzate e, quindi, distaccate dalle fiasche di coltura. La cellularità ottenuta è, quindi, marcata con appositi anticorpi ed è analizzata al citofluorimetro per ottenerne dati micromorfologici ed immunoistochimici. Dal punto di vista clinico, il PRP viene testato in rapporto a difetti cistici odontogeni apicali (resistenti alla terapia endodontica e di diametro * di 2cm) e di siti atrofici mascellari bilaterali (grado IV-VI secondo Cawood e Howell) sovrapponibili. Il PRP è testato da solo come gel di riempimento, in alcuni difetti cistici, addizionato ad osso autologo, in altri difetti cistici ed in uno dei due seni mascellari. Tali interventi vengono confrontati tra loro ed in rapporto al solo osso autologo, rispettivamente, impiegato come riempitivo in altri difetti cistici e nei sinus lift nel seno mascellare controlaterale a quello in cui l’osso era utilizzato con PRP. Scopo del lavoro era precisare gli effetti del PRP in rapporto alla rigenerazione ossea. I risultati ottenuti dimostrano la capacità, in vitro, del PRP di generare colture complete di tessuto calcifico ove, diversamente, si ottengono quasi esclusivamente fibroblasti. Micromorfologicamente, la cellularità coltivata con PRP presenta una volumetria ed una densità cellulare comparabile a quella osteoblastica ed anche il mosaico antigenico rilevato, ed in particolare la glicoproteina CD38, fanno pensare ad un’attivazione cellulare probabilmente in tal senso. I rilievi clinico/radiologici (anche densitometrici) ed istologici fanno pensare che il PRP possa supportare, prevalentemente processi di accelerazione della neorigenerazione tissutale. Codici: ISSN: 0177-3348 (Print) - 0177-3348 (Linking) – Altre ID: (DNLM)SR0058226(s) - (OCoLC)28226223 NLM ID: 9426456 [Serial]

2001 - Studio preliminare dell’efficacia del PRP in chirurgia rigenerativa [Relazione in Atti di Convegno]
Consolo, Ugo; Bellini, Pierantonio; Bertoldi, Carlo; Zaffe, Davide
abstract

La stadiazione della capacità rigenerativa ossea mediata dal Platelet-rich Plasma (PRP) è l’obbiettivo di questo studio condotto su 18 pazienti affetti da cisti odontogena flogistica apicale (resistente alla terapia endodontica e di diametro * 2cm) e 8 pazienti necessitanti di sinus lift. Questi soggetti selezionati per essere rigorosamente omogenei tra loro e nell’ambito della stessa patologia, venivano divisi in sottogruppi a seconda del tipo di trattamento cui sarebbero stati sottoposti. I soggetti affetti da cisti, quindi, erano suddivisi in 3 sottogruppi: un primo sarebbe stato sottoposto ad exeresi cistica e ad innesto osseo autologo, un secondo ad exeresi cistica ed a innesto di osso autologo addizionato a PRP ed un 3° sottogruppo, ad innesto di solo GEL di PRP dopo l’exeresi cistica. Degli 8 soggetti sottoposti a procedura di sinus lift, 3 erano di 4° grado, 4 di 5° grado ed 1 di 6° grado di atrofia maxillo-sinusale secondo Cawood e Howell. Ognuno di tali soggetti doveva presentare bilateralmente le stesse caratteristiche atrofiche al fine di poter confrontare un tipo di intervento con l’altro e disporre così di un’accurato sistema per cogliere differenze. Così, in modo assolutamente randomizzato, in un seno mascellare il sinus lift è stato compiuto con solo innesto di osso autologo (secondo una procedura chirurgica ormai consolidata) e nel controlaterale il rialzo è stato compiuto trattando l’innesto (uguale volumetricamente) con PRP. Nei sottogruppi cistici, monitorizzazioni cliniche e radiologiche sono state compiute nel pre-intervento e a 2, 3, 4, 5 e 6 mesi dall’intervento. Nel caso delle procedure di sinus lift, tali monitorizzazioni avevano una tempistica simile alla precedentemente descritta se non perché, nel post-intervento, cominciavano ad essere eseguite a 3 mesi (e non 2) dall’intervento poiché si era fatto in modo che potessero coincidere con l’innesto implantare. Nelle diverse fasi del post-intervento sono state ricavate anche delle biopsie tramite fresa trephine. IL PRP si dimostra sicuramente un mezzo in grado di agevolare alcune procedure chirurgiche di compattamento degli innesti, un buon sistema per il controllo emorragico (come già facevano altri gel come quelli a base di fibrina) ed in grado di sortire buoni effetti nel controllo delle reazioni flogistiche post-chirurgiche. La sua capacità osteorigenerativa, invece, appare limitata dalle influenze ambientali biologiche e pare degradare nel tempo non rendendo stabili i guadagni ossei ottenuti quando questi si trovino in situazioni biologicamente sfavorevoli (es.: innesti per sinus lift).

2001 - Tavole di Istopatologia del cavo orale: III - Tipologia dei connettivi. Seconda parte – Le fibre e la sostanza intercellulare amorfa. [Articolo su rivista]
Zaffe, Davide; Botticelli, A. R.
abstract

N.D.

2001 - Tavole di Istopatologia del cavo orale: III - Tipologia dei connettivi. Terza parte - Tessuto adiposo e midollo osseo. [Articolo su rivista]
Zaffe, Davide; Botticelli, A. R.
abstract

N.D.

2000 - Camera riassorbibile per la rigenerazione guidata nel trattamento delle ampie perdite di sostanza diafisarie: studio sperimentale nel coniglio [Capitolo/Saggio]
R., Giardino; N., Nicoli Aldini; G., Giavaresi; M., Fini; P., Di Denia; L., Martini; Canè, Valerio; Zaffe, Davide
abstract

Volume con contributi di studi su biomateriali

2000 - Clinical evaluation, radiologic and histologic analysis in mandibular alveolar distraction procedures. Preliminary study Valutazioni cliniche, analisi radiologiche ed istologiche nelle procedure di distrazione alveolare mandibolare. Studio preliminare. [Articolo su rivista]
Consolo, Ugo; Bertoldi, Carlo; Urbani, G; Zaffe, Davide
abstract

Obiettivo: La distrazione osteogenetica alveolare (DOA) è quel processo che conduce a formazione di nuovo osso alveolare, rimediando così a dismorfismi crestali in altezza e in larghezza. Scopo di questo lavoro è lo studio sui processi ossei al fine di ottimizzare i tempi di riabilitazione protesica implantare.Metodi: Sette soggetti con insufficienza crestale sono stati trattati con DOA per ottenere l’incremento crestale desiderato. Valutazioni cliniche ed esami radiologici erano eseguiti per le successive 12 settimane prima dell’inserzione degli impianti. Biopsie a 40, 60 e 88 giorni venivano studiate con metodi di colorazione generali, specifici per l’osso, istochimici e su microradiografie, analizzate per il Trabecular Bone Volume.Risultati: Dopo 40 giorni il callo fibroso mostra la presenza dell’inizio della ossificazione. A 60 giorni il trabecolato è formato da osso a fibre intrecciate con attività osteogenetiche basse, occupante metà della biopsia. A 88 giorni la quantità di osso presente appare più ridotta, la struttura corrisponde a tessuti più ordinati, le attività di osteoformazione sono ulteriormente ridotte mentre l’erosione osteoclastica risulta attiva.Conclusioni: I risultati evidenziano uno steady-state delle biopsie a 60 giorni dalla fine della distrazione e una loro regressione con tempi successivi. I risultati, pertanto, sembrano suggerire una inserzione anticipata degli impianti al fine di evitare la perdita di osso a causa dell’assenza di sollecitazioni meccaniche. PMID: 11268936

2000 - Comportamento dell’osso adiacente impianti Tioblast dopo test push-in [Capitolo/Saggio]
Zaffe, Davide; R. Rodriguez y., Baena; S., Rizzo; C., Brusotti
abstract

Volume con contributi di studi su biomateriali

2000 - Distrazione osteogenetica alveolare della mandibola: Valutazioni cliniche, radiologiche e istologiche. [Relazione in Atti di Convegno]
Consolo, Ugo; Bertoldi, Carlo; Zaffe, Davide
abstract

La distrazione osteogenetica alveolare (ADO) è quel processo che conduce a formazione di nuovo osso alveolare, rimediando così a dismorfismi crestali in altezza e in larghezza. Scopo di questo lavoro è lo studio sui processi ossei al fine di ottimizzare i tempi di riabilitazione protesica implantare. Sette soggetti con insufficienza crestale sono stati trattati con ADO, mediante distrattori intraorali extra-alveolari, per ottenere l’incremento crestale desiderato. Valutazioni cliniche ed esami radiologici erano eseguiti per le successive 12 settimane prima dell’inserzione degli impianti. Biopsie a 40, 60, 88 e 200 giorni venivano studiate con metodi di colorazione generali, specifici per l’osso, istochimici e su microradiografie, analizzate per il Trabecular Bone Volume (TBV). Dopo 40 giorni il callo fibroso mostra la presenza dell’inizio della ossificazione. A 60 giorni il tessuto fibroso è completamente convertito in un trabecolato osseo formato tessuto a fibre intrecciate nel quale le attività osteogenetiche risultano limitate, con TBV di circa il 50%. A 88 giorni il tessuto osseo mostra porzioni a struttura più ordinata (osso a fibre parallele ed osso lamellare). Le attività osteoformative più ridotte e la maggior erosione osteoclastica portano ad una riduzione del 25% della massa scheletrica non evidenziabile con la CT-dental scan. Le analisi densitometriche, tuttavia, indicano un costante incremento della densità minerale ossea dopo l'inserimento degli impianti. In conclusione, i risultati evidenziano uno steady-state delle biopsie a 60 giorni dalla fine della distrazione e una loro regressione con tempi maggiori. Normalmente la natura "parte" ponendo a disposizione una più abbondante massa di tessuto non molto maturo nè organizzato riservandosi, poi, sulla base di precise esigenze funzionali, di eliminare il tessuto superfluo e di organizzare il restante. E' quello cui abbiamo assistito nel callo osseo esaminato, fuorchè non siamo affatto certi che il modello di carico corrispondente al segmento edentulo nel cui ambito il callo è maturato sia simile a quello che lo stesso segmento dovrà avere dopo che gli impianti e la bonifica protesica saranno stati, rispettivamente, inseriti e completata. I risultati, pertanto, sembrano suggerire la possibilità di una inserzione anticipata degli impianti al fine di evitare la perdita di osso e "deviazioni" maturative a causa della presenza di inadeguati stimoli meccanici.

2000 - Do osteocytes intervene in regulating osteoclast activity?. [Abstract in Rivista]
Palumbo, Carla; Ferretti, Marzia; Zaffe, Davide; Marotti, Gastone
abstract

Osteocyte could intervene in the process of bone resorption.

2000 - DOA mandibolare: studio clinico, radiologico e istologico. [Abstract in Atti di Convegno]
Consolo, Ugo; Bertoldi, Carlo; Zaffe, Davide
abstract

Scopo di questo studio è contribuire all’ottimizzazione delle procedure di Distrazione Ossea Alveolare (DOA) nella mandibola. Si sono voluti anche verificare i possibili vantaggi che il sistema distrattivo poteva presentare rispetto a quelle procedure attuate precedentemente nei medesimi frangenti, come ad esempio gli innesti ad "onlay" e ad "inlay". L'induzione ossea del sistema distrattivo, infatti, rappresenterebbe, anche dal punto di vista teorico, un "optimum" in quanto si tratterebbe di un difetto a "quattro pareti" con una quinta parete costituita dda periostio integro ed un "pabulum" osteoinduttivo" rappresentato dal callo osseo di una settimana. Il confronto di altri sistemi con questo "ideale" difficilmente condurrà a pari risultati ed è per questo che si è proceduto a confrontare il livello di maturazione ossea raggiunto con il sisitema distrattivo ad alcuni casi di innesto ad "inlay" trattato con Platelet-Rich Plasma (PRP). Dieci pazienti (che avevano dato il loro consenso informato allo studio in oggetto) affetti da deformità mandibolari crestali sono stati sottoposti a DOA con distrattore intraorale extra-alveolare. Il distrattore è stato rimosso 8 settimane dopo la fine della fase distrattiva e gli impianti sono stati inseriti 4 settimane più tardi. Controlli clinici e radiologici sono stati eseguiti prima del trattamento chirurgico iniziale e nelle fasi successive. Prelievi bioptici per analisi istologiche e microradiografiche, con valutazione del Trabecular Bone Volume (TBV), sono stati eseguiti a 40, 60, 88 e 200 giorni dal termine della distrazione. Il callo soffice mostra l’inizio dell’ossificazione a 40 giorni mentre a 60 giorni esso si è trasformato in una fitta rete di trabecole ossee a fibre intrecciate (TBV 49,5%). Oltre i 60 giorni, accanto ad una più ordinata neoformazione ossea si osserva una spiccata erosione osteoclastica (decremento del 25% del TBV a 88 giorni). L’analisi densitometrica mostra un progressivo incremento della mineralizzazione ossea dopo il termine della fase distrattiva. Sei pazienti trattati con innesti ossei ad "onlay", "inlay" ed "inlay" midollare con PRP furono valutati nello stesso modo del callo osseo dei soggetti sottoposti a distrazione. I confronti operati agli stessi tempi mostravano quadri di "maturazione" ossea decisamente più arretrati nel caso degli innesti (il quadro era leggermente più sfavorevole per gli innesti ad "onlay"), mentre le preliminari valutazioni dei casi ad "inlay" con il PRP risultano assai più confortanti. I "numeri", tuttavia, sono ancora esigui per procedere ad una definitiva valutazione in questo senso. Per quanto riguarda la DOA i risultati ottenuti paiono indicare la necessità di provvedere il segmento osseo distratto di almento un modello di carico congruente con quello definitivo al fine di conseguire la corretta maturazione del callo. Codice: IT\ICCU\BVE\0214063

2000 - Effetto del calcitriolo sulla velocità dello spostamento dentario e sul tessuto osseo in corso di trattamento ortodontico in ratti giovani ed adulti. [Articolo su rivista]
Giunta, D; Zaffe, Davide
abstract

Scopo della presente ricerca è valutare l’effetto del calcitriolo sulla velocità dello spostamento dentario e sul tessuto osseo in corso di trattamento ortodontico in ratti giovani ed adulti. Lo studio è stato eseguito su un totale di 80 ratti albini outbred Wistar maschi: 38 giovani (11-13 settimane di età) e 42 adulti (22-27 settimane di età). Un’inclinazione mesiale del primo molare superiore veniva ottenuta mediante l’applicazione di molle chiuse di nickel-titanio che liberavano una forza di 25 cN, applicate tra gli incisivi ed il primo molare. Gli animali, giovani ed adulti, comprendevano un gruppo di controllo ed un gruppo sperimentale suddiviso a sua volta in quattro gruppi in base alla durata del trattamento ortodontico: 3, 7, 14 e 21 giorni. Ad eccezione del gruppo di controllo tutti ricevevano, ogni tre giorni, un’iniezione intramucosa di 20 ml di calcitriolo (Calcijex, 10 –10 mol/L) a livello della superficie palatale mesiale del primo molare superiore di sinistra. Nel lato opposto veniva iniettato un uguale volume di PBS. Una parte degli animali trattati per 21 giorni subiva un trattamento aggiuntivo di tetraciclina allo scopo di ottenere la marcatura dell’osso in formazione. Nei soggetti adulti il movimento dentario sul lato sperimentale, che riceveva l’iniezione di calcitriolo, è risultato maggiore del 160 % (p<0,001) rispetto al lato trattato con solo PBS dopo 21 giorni di trattamento. In corrispondenza del lato sperimentale è stata osservata una più diffusa fluorescenza dell’osso alveolare compreso tra primo e secondo molare e della parete alveolare vestibolare dell’osso mascellare. L’analisi istochimica dell’attività osteoclastica, valutata su sezioni colorate per la fosfatasi acida tartrato resistente (TRAP), indica, nel lato sperimentale, una maggiore estensione delle aree interessate dall’erosione degli osteoclasti in animali adulti con tempo di trattamento di 3 giorni. L’analisi delle microradiografie delle sezioni dell’osso alveolare evidenzia che tessuto non calcificato risulta quantitativamente maggiore nel lato sperimentale rispetto al lato di controllo. La somministrazione di calcitriolo non presenta alcuna indicazione nei ratti giovani nei quali l’effetto del calcitriolo non sembra produrre variazioni della velocità dello spostamento dentario.

2000 - Element embedding in soft and hard tissues surrounding medical devices. [Abstract in Rivista]
Zaffe, Davide; Bertoldi, Carlo; Consolo, Ugo
abstract

Gli autori, anche tramite metodiche di scansione elettronica e di microanalisi per “salto quantico” intendono analizzare la possibile dispersione tissutale di elementi a partire da impianti e placche con viti per fissazione interna rigida. La ricerca evidenzia un esteso quadro di diffusione di microcostituenti dai materiali analizzati. In questo ambito i materiali diffusi tendono ad essere rilevati con una particolare “mappatura” tissutale la cui identificazione etiopatologica dovrà essere oggetto di successive ricerche. Secondo il punto di vista clinico, da questi dati preliminari, la diffusione di microcostituenti appare essere spesso indipendente da coesistenti segni clinici di flogosi tissutale. 32) Bertoldi C., Zaffe D., Bellini P., Consolo U.: Elementi metallici nei tessuti circondanti dispositivi per fissazione interna rigida (FIR). Minerva Stomatologica 2001; 50(5): 121-32. – ISSN: 0026-4970 L’impiego di dispositivi alloplastici al riguardo del distretto oro-maxillo-facciale è sempre più diffuso in rapporto alle possibilità che la scienza e la ricerca rendono disponibili per le più svariate esigenze cliniche e chirurgiche in campo odontostomatologico e maxillo-facciale. Per quanto riguarda i dispositivi metallici, i diversi elementi che costituiscono le leghe sono stati riscontrati soprattutto in diversi organi, ma, anche se con un minor numero di studi esaurientemente condotti, pure localmente nei tessuti circondanti i dispositivi stessi. Scopo del presente studio è l’analisi dei tessuti circostanti i dispositivi per fissazione interna rigida (FIR), impiegati in chirurgia orale pre-protesica ed in chirurgia maxillo-facciale, al fine di evidenziare la diffusione di elementi, analizzando la morfologia delle particelle liberate e studiando il comportamento dei tessuti. I pazienti furono suddivisi in 5 gruppi in rapporto al grado flogistico rilevato localmente. Il materiale bioptico fu ricavato da 18 pazienti (20-76 anni di età), portatori di griglie, placche e viti per FIR da 4 mesi a 9 anni. La microscopia ottica, a scansione elettronica e la microanalisi a raggi x (EDS system) furono utilizzati nello studio morfologico e nell’identificazione delle particelle metalliche e degli elementi. I risultati indicano chiaramente che particelle metalliche o elementi mobilizzati da placche, viti o griglie possono generare diffusione tissutale e/o uptake cellulare. Non solo cromo, ferro od alluminio ma anche il titanio può facilmente essere rilasciato dai dispositivi ed accumularsi nei tessuti. La diffusione del titanio è particolarmente evidente nel tessuto fibroso circostante i dispositivi per FIR. L’alluminio non solo mostra una maggiore persistenza nel tessuto fibroso, ma sembra esibire un peculiare comportamento di accumulo nell’osso lamellare. Il grado flogistico locale sembra essere strettamente correlato alla metallosi. Non solo cromo, ferro ed alluminio, ma anche il titanio, sebbene con diverso grado, possono originare effetti flogistici. La metallosi e la flogosi danno, probabilmente, origine ad un processo a cascata nel quale possono essere sia causa che effetto allo stesso tempo. Il deciso rilascio di titanio, che normalmente non sembra produrre effetti flogistici clinici (come quelli, per esempio mediati dall’alluminio) così come il modello di diffusione dell’alluminio in ambito osseo, necessitano senz’altro di ulteriori approfondimenti circa i loro effetti su tessuti e cellule.

2000 - GBR in chirurgia implantare immediata post-estrattiva. [Articolo su rivista]
LEGHISSA G., C; BOTTICELLI A., R; Zaffe, Davide
abstract

N.D.

2000 - Histomorphometric analysis of osteoclast effect on osteocyte viability [Abstract in Atti di Convegno]
Palumbo, Carla; Ferretti, Marzia; Zaffe, Davide; Ardizzoni, Andrea; Marotti, Gastone
abstract

2000 - Il ruolo degli osteociti nel controllo dell’omeostasi scheletrica perimplantare [Capitolo/Saggio]
A. E., Bianchi; F., Sanfilippo; Zaffe, Davide
abstract

Volume di contributi di studi su biomateriali

2000 - Neuroprotective effect of gamma-hydroxybutyrate in transient global cerebral ischemia in the rat [Articolo su rivista]
Vergoni, Anna Valeria; Ottani, Alessandra; Botticelli, A. R.; Zaffe, Davide; Guano, L.; Loche, A.; Genedani, Susanna; Gessa, G. L.; Bertolini, Alfio
abstract

The effect of gamma-hydroxybutyrate on the histological and behavioral consequences of transient brain ischemia was studied in the four vessel occlusion rat model. In saline-treated animals, 30 min ischemia caused a massive loss of neurons in the hippocampal CA1 subfield (normal neurons: 14%, 5%, 23% and 30% on the 3rd, 10th 15th and 65th day after ischemia, respectively). gamma-Hydroxybutyrate - 300 mg/kg intraperitoneally (i.p.) 30 min before or 10 min after arteries occlusion, followed by 100 mg/kg i.p. twice daily for the following 10 days - afforded a highly significant protection (normal neurons on the 3rd, 10th, 15th and 65th day after ischemia: 88% and 91%, 80% and 80%, 91% and 90%, 72% and 71% in rats receiving the first dose before or after arteries occlusion, respectively). The ischemia-induced sensory-motor impairment was significantly attenuated in rats receiving the first dose of gamma-hydroxybutyrate before arteries occlusion. Finally, the ischemia-induced impairment in spatial learning and memory, evaluated starting 27 days after the ischemic episode, was significantly attenuated by gamma-hydroxybutyrate, either injected first at 30 min before or 10 min after arteries occlusion. Lower doses of gamma-hydroxybutyrate had no significant effect. In conclusion, these results indicate that gamma-hydroxybutyrate provides significant protection against both histological and behavioral consequences of transient global cerebral ischemia in rats. (C) 2000 Elsevier Science B.V. All rights reserved.

2000 - Presenza di elementi metallici nei tessuti circondanti mezzi di osteosintesi per FIR [Capitolo/Saggio]
Zaffe, Davide; Bertoldi, Carlo; Consolo, Ugo
abstract

Volume con contributi di studi su biomateriali

2000 - Studio preliminare dell’utilizzo del gel di piastrine autologo in chirurgia maxillo-facciale. [Abstract in Rivista]
Ceccherelli, G. B.; Bertoldi, Carlo; Bellini, Pierantonio; Zaffe, Davide; Cossarizza, Andrea; De Palma, M.; Consolo, Ugo
abstract

Vedasi l'allegato

2000 - Tavole di Istopatologia del cavo orale: II - Tipologia degli epiteli ghiandolari. Terza parte – Cellule mioepiteliali e membrane basali. [Articolo su rivista]
Zaffe, Davide; Botticelli, A. R.
abstract

N.D.

2000 - Tavole di Istopatologia del cavo orale: III - Tipologia dei connettivi. Prima parte – Connettivo lasso. [Articolo su rivista]
Zaffe, Davide; Botticelli, A. R.
abstract

N.D.

1999 - Distraction osteogenesis of mandibular bone: clinical, radiological and histological evaluation. [Abstract in Atti di Convegno]
Consolo, Ugo; Bertoldi, Carlo; Zaffe, Davide; Urbani, G.
abstract

Circa i processi che sono chiamati in causa nella formazione e nella guarigione del callo osseo, le conoscenze sono a tuttoggi, a dir poco, imperfette. In realtà non conosciamo neppure dettagliatamente ciò che avviene nei processi si ossificazione. Si sa con sicurezza che all'inizio, sia nei modelli ossificativi membranosi che encondrali (ed in quest'ultimo caso, nella fase che anticipa lo "stampo" cartilagineo), all'inizio esiste un tessuto connettivoide con le fibre rivolte nelle varie direzioni dello spazio e dotato di poche lacune e, quindi, di un'ampia densità di tessuto per unità di campo esaminato. Nelle strutture ossee mature, invece, il rigore del parallelismo che assumono le fibre tra loro assieme all'esistenza di una struttura più evoluta da un punto di vista biochimico (ne sono un esempio i livelli di calcificazione come calcificazione) ed all'ampio numero di lacune presenti (bassa densità tissutale per unità di campo), fanno pensare ad una struttura perfettamente evoluta in rapporto ad un particolare, ridotto numero di modelli di carico rispetto alla primigena che poteva adattarsi, ma con una minore "resa", ad una pluralità di modelli di carico meccanico. Scopo di questo lavoro era di conseguire un monitoraggio il più possibile accurato (e quindi utilizzando osservazioni cliniche, radiologiche ed istologiche) del callo rigenerativo al fine di migliorare, se possibile, il protocollo applicativo della correzione distrattiva del difetto osseo. Uno studio clinico, radiologico ed istologico fu eseguito su 10 pazienti di età variabile tra i 15 ed i 74 anni (al momento dell'intervento) impiegando distrattori intraorali extra-alveolari ed intraorali intra-alveolari. Il protocollo di attivazione dei distrattori e le conseguenti valutazioni cliniche, radiologiche ed istologiche era già stato codificato (ed esplicato nei precedenti lavori). Sulle varie biopsie, però, vennero preparate varie sezioni spesse (circa 100 *m), adatte alle procedure microradiografiche. Per ogni microradiografia, tramite un analizzatore d'immagine, venne calcolato in valori percentuali il Trabecular Bone Volume (TBV). Al di là di osservazioni già compiute in precedenti studi, di particolare interesse furono, in questo caso, le valutazioni conseguite mediante analisi del TBV su sezioni spesse per microradiografie e mediante valutazioni sul grado di mineralizzazione mediante densitometria in unità HU. Il TBV, infatti, era in grado di darci una misurazione significativa della densità di tessuto per unità di campo mentre la densitometria ci mostrava il grado di "maturazione" biochimica ossea. Dopo il sessantesimo giorno dalla fine della distrazione ossea il TBV calava drasticamente mentre, dal momento della fine della distrazione, con un andamento costante (inversamente proporzionale all'età del paziente) si assisteva all'incremento densitometrico del callo osseo. Tutto questo ci portava a concludere che stavamo assistendo alla maturazione del segmento osseo distratto in una fase precedente all'implantologia.

1999 - Effects of essential amino acids and lactose on bony fractures and defects in rabbits: a preliminary histomorphometric study [Articolo su rivista]
M., Fini; N., Nicoli Aldini; Canè, Valerio; Zaffe, Davide; G., Giavaresi; M., Rocca; G. A., Guzzardella; R., Giardino
abstract

An experimental study was performed in order to test the possibility of improving bone repair with the administration of a drug (Calciofix, Farmaceutici Damor SpA, Naples, Italy) containing essential amino acids and lactose. Fifty rabbits were submitted to an open transversal fracture of the left fibula and to a right femoral condyle defect. They were left untreated or treated daily with the drug orally and were divided into subgroups depending on the experimental time: 15, 30, 40, 50, 60 days. Histomorphometric data showed a significantly faster healing rate in treated animals compared with untreated ones. Firstly, on day 30 there was a significantly larger amount of cartilage in the control bone callus (P < 0.01). On day 50 a significant difference existed between trabecular and lacunar percentages in the two subgroups (P < 0.0005). At 60 days no significant differences were observed, but bony trabeculae had become more oriented parallel to the long axis of the bone in treated animals. Secondly, after 15 days the defect area was significantly smaller in treated animals than in the untreated ones (P < 0.01). At 30 and 40 days, respectively, significant differences existed between the two subgroups in connective tissue and mature bone percentages (P < 0.01 and P < 0.001). Our results seem to demonstrate that the drug significantly accelerates the rate of bone formation in fractures and bone defects in rabbits.

1999 - Esperiences of alveolar bone distraction by intraoral devices: clinical, radiographic and morphologic analyses. [Abstract in Atti di Convegno]
Consolo, Ugo; Bertoldi, Carlo; Zaffe, Davide; Urbani, G.
abstract

La patologia difettiva della cresta alveolare è un reperto comune della patologia deformativa orale. Tra i più frequenti motivi etiologici vanno ricordate le sequele avulsive. Uno studio clinico, radiologico ed istologico fu eseguito su 7 pazienti di età variabile tra i 15 ed i 74 anni (al momento dell'intervento) impiegando distrattori intraorali extra-alveolari ed intraorali intra-alveolari. Il distrattore veniva inserito, a seconda del tipo impiegato, mediante le procedure usuali che richiedevano, dopo l'osteotomia, il fissaggio vestibolare del distrattore, nel caso dell'impiego della varietà extra-alveolare, o l'apertura di un alveolo di tipo implantare, nel caso della varietà intra-alveolare. Dopo un periodo di latenza di circa una settimana i distrattori venivano attivati sino a raggiungere le correzioni crestali desiderate e quindi lasciati in sito diasattivati. Tutti i pazienti furono sottoposti a controllo clinico, radiologico (mediante proiezioni usuali e CT con dental scan e densitometria sul sito ogetto di distrazione) ed a valutazioni istologiche. Le valutazioni cliniche e radiologiche furono eseguite pre-operatoriamente e durante le fasi essenziali della distrazione e della successiva bonifica implantologica mentre le biopsie sul callo furono eseguite a 40, 60, 88 e 200 giorni dalla fine della distrazione. Da un punto di vista clinico non emersero mai problemi veramente rilevanti. Tuttavia si osservava l'insorgenza di algia durante l'attivazione nel conseguimento degli ultimi millimetri di correzione. In tali casi si provvedeva a frammentare ulteriormente nella giornata la quota di distrazione impostata od a ridurla nei casi più gravi. Negli apparechi extra-alveolori, poi, al termine della distrazione si osservava quasi costantemente l'obliterazione del vestibolo per un effetto di "trascinamento" dei tessuti molli. Ciò richiedeva un ulteriore intervento correttivo. Per quanto riguardava i distrattori intra-alveolari, invece, potevano manifestarsi fenomeni di "cedimento" alla distrazione con alterazione conseguente dei vettori distrattivi e del successo conseguibile ed, inoltre, era impossibile distrarre al ritmo degli extra-alveolari. Gli extra-alveolari, poi, consentivano, in funzione della loro rigidezza, la pre-determinazione della vettorialità della distrazione, qualità inconseguibile con gli intra-alveolari. I rilievi radiologici ed istologici indicano una sorta di "stady-state" osseo a partire da 60 giorni dal termine della distrazione.

1999 - Guided bone regeneration using titanium grids: report of ten cases. [Articolo su rivista]
Leghissa, G. C.; Zaffe, Davide; Assenza, B.; Botticelli, A. R.
abstract

In order to ensure an adequate space where new bone can be formed in guided bone regeneration (GBR), most surgeons fill bone defects with biomaterials. In this work we evaluated new bone regeneration in 10 patients using only a blood clot protected with titanium grids and non-resorbable membranes, without any filling material. A manual measurement of the size of the bone defect, using a plastic probe, was performed at 2 surgical steps. After 5 months of treatment, a biopsy was taken from each patient, fixed and embedded in PMMA, examined microradiographically and morphologically to evaluate the newly-formed bone. Our results showed a good repair of the defects by bone regeneration (about 85% overall), high mineral density of new bone around the implants after 5 months, and steady state deposition processes. These results in GBR, without filling material, appear very promising for implantology and reconstructive odontostomatology practice.

1999 - Histologic features of osteogenesis in the alveolar bone distraction [Relazione in Atti di Convegno]
Consolo, Ugo; G., Urbani; Bertoldi, Carlo; Zaffe, Davide
abstract

Alveolar bone distraction was performed for 5 to 13 days on seven patients using a Martin device, removed 12 weeks after the end of distraction. Biopsies were carried at device removal and before placing implants. All patients had a good response to surgery. Histology showed a good vascular network and start of ossification 40 days after the end of distraction. Soft callus was widely converted into a network of trabecular woven bone at 60 days. Biopsies are almost completely constituted by trabeculae of woven bone lined by more ordered bone at 170 days. No osteoclast activity was detected after 60 days. Alkaline phosphatase activity, not yet appreciably high after 60 days, is very low at 170 days. In conclusion, these preliminary results, indicating an almost steady-state bone deposition processes, suggest the possibility of an early implant insertion. ISI WOS:000081376000020 IDS Number: BN25Y

1999 - Histomorphometric study of bone reactions during orthodontic tooth movement in rats [Articolo su rivista]
C., Verna; Zaffe, Davide; G., Siciliani
abstract

The biological response to orthodontic tooth movement has generally focused on reactions within the periodontal ligament (PDL), whereas less attention has been paid to the behavior of neighboring bone. The purpose of the study was to describe the influence of orthodontic force on bone surrounding the displaced tooth and the adjacent, untreated teeth, Bone changes in relation to treatment time and different sites were investigated. A mesial tipping of the left maxillary first molar was obtained from 54 adult male Wistar rats. Oxytetracycline was injected subcutaneously 48 h before killing, which took place after 4, 7, or 14 days. The maxilla was fixed in paraformaldehyde and embedded undecalcified in methylmethacrylate, A set of thick horizontal sections was taken from the cervical, intermediate, and apical levels of the roots. The sections were microadiographed and analyzed microscopically under bright-field and fluorescent illumination. Bone fraction and PDL width was measured using a Zeiss Videoplan device equipped with an overlay system. New bone formation was detected by oxytetracycline labels. The analysis showed a consistent, significant decrease of the alveolar bone fraction around both displaced and adjacent teeth at ail treatment times, Apposition, indicated by the tetracycline uptake, was found on the periosteal side of the treated hemimaxilla and, after 14 days, also on the surface toward which the tooth was moving and around the adjacent teeth. These results suggest that a time rather than a space relationship exists between bone resorption and formation and that the whole hemimaxilla reacts to the mechanical challenge, resembling the regional acceleratory phenomenon (RAP) observed in other circumstances. (C) 1999 by Elsevier Science Inc. All rights reserved.

1999 - Implantologia e Implantoprotesi - Basi biologiche, Biomeccanica, Applicazioni cliniche [Monografia/Trattato scientifico]
A. E., Bianchi; F., Sanfilippo; Zaffe, Davide
abstract

CAP. 1 - BASI BIOLOGICHE - Istofisiopatologia del tessuto osseo- Istogenesi causale del tessuto osseo- Ossificazione intramembranosa- Ossificazione encondrale- Accrescimento in lunghezza delle ossa- Accrescimento diametrale delle ossa- Riorganizzazione interna dell'osso- Livelli organizzativi del tessuto osseo- Matrice dell'osso- Matrice inorganica- Matrice organica: la componente fibrillare- Matrice organica: la componente non fibrillare- Cellule dell'osso- Linea di derivazione degli osteoblasti- Linea di derivazione degli osteoclasti- Osteoblasti- Osteociti- Processo di trasformazione dell'osteoblasta in osteocita- Funzioni dell'osteocita- Cellule di rivestimento- Osteoclasti- Organizzazione funzionale delle cellule ossee- Tessuti ossei- Osso primario o di addizione- Osso secondario o di sostituzione- Osso a fibre intrecciate- Osso a fibre parallele- Osso lamellare- Architettura dell'osso- Architettura compatta- Supporto vascolare- Circolazione microcavitaria- Funzioni delle cellule ossee- Considerazioni clinico-biologiche sull'adattamento osseo- Adattamento osseo e influenze biofisiche- Agenti mitogeni- Aspetti dinamici dell'architettura e della struttura dell'osso- Realzioni tra sollecitazioni deformanti e risposta cellulare- Deformazioni e adattamento osseo- Meccanocettori e chemocettori ossei- Sequenze di coordinazione cellulare nel rimaneggiamento osseo- Modulazione dell'attività di rimaneggiamento osseo- Controllo traiettoriale dell'attività cellulare- Biologia della riaparazione delle lesioni traumatiche- Emostasi e danno anossico- Flogosi, invasione e induzione cellulare- Rimozione dell'ematoma e dei tessuti necrotici- Blastema fibrocellulare- Osteogenesi e rimodellamento- Riparazione della ferita chirurgica attorno agli impianti dentali- Incorporazione degli impianti: protocolli line-to-line versus protocolli press-fit- Presupposti per la valutazione della riparazione della ferita chirurgica attorno a impianti bioinerti in titanio- Stadiazione della riparazione della ferita implantare- Indagini istologiche comparate per l'analisi del substrato osseo perimplantareCAP. 2 - ASPETTI BIOMECCANICIASPETTI MORFOSTRUTTURALI DELL'OSSO PERIMPLANTARE- I biomateriali- Interfaccia osso titanio- Reperimento di campioni bioptici umani- Organizzazione architetturale e tissutale dell'osso perimplantare- Morfologia della superficie ossea all'interfaccia- Competenza biomeccanica del substrato di sostegno e stabilità tissutale- Propagazione delle sollecitazioni dell'impianto al substrato- Adattamento strutturale in relazione alla gemotria implantare- Perdita dell'anchilosi funzionale- Rapporti funzionali tra osso e impianto- Unità osso impianto - Ampiezza biologica- Analogie tra impianti ortopedici e dentali- Caratteristiche dei biomateriali e rapporti di superficie- Dinamica della riparazione della ferita chirurgica- Periodo iniziale postchirurgico - Periodo intermedio postchirurgico - Periodo postchirurgico tardivo- Rapporti morfostrutturali tra osso e impianti a distanza di tempo- Potenzialità rigenerative del tessuto osseo attorno a impianti ortopedici- Considerazioni sull'organizzazione ossea perimplantareAPPLICAZIONI CLINICHECHIRURGIA SPECIALE IMPLANTOLOGICA- Evoluzione delle ossa mascellari in seguito all'edentulia- Zona interforaminale- Zona periforaminale- Zona posteriore- Zona frontale- Zona del pilastro canino- Zona subantrale- Zona del tuber e pilastro pterigoideo- Limiti dell'età- Osteoporosi- Diagnostica tridimensinale mediante TC in associazione a placche di guida- Aspetti decisionali chirurgici- Placche di guida chirurgiche- Intervento chirurgico- Aspetti decisionali biologici- Importanza della gengiva cheratinizzata- Management dei tessuti molli perimplantari- Aumento della gengiva aderente- Innesto libero epitelio-connetivale- Innesto libero connettivale- Formazione di pseudopapille interimplantari- Condizioni determinanti il protocollo implantare- Impianti nella zona p

1999 - Induction and pharmacological treatment of oral osteopenia in rats. [Articolo su rivista]
Zaffe, Davide; C., Paganelli; D., Cocchi
abstract

L'osteoporosi, per l'elevato costo sociale dovuto alle fratture di cui è causa, rappresenta probabilmente il maggior problema di salute pubblica. La perdita di osso orale ha, in più, un'enorme importanza sulla qualità di vita dei pazienti, essendo presente in modo più o meno accentuato nel 90% degli individui anziani. Lo scopo di questo lavoro è stato quello di predisporre un modello animale di osteoporosi in cui valutare la perdita di osso orale e la sua possibile prevenzione tramite trattamento farmacologico. Ratti adulti Sprague-Dawley, dopo gonadectomia, vennero trattati con clodronato (maschi), con estrogeni (femmine), o con il solo veicolo per due mesi. Dopo fissaggio e inclusione in metacrilato delle ossa mandibolare e mascellare, le microradiografie delle sezioni seriate furono analizzate istomorfometricamente tramite Zeiss VIDAS. In entrambi i sessi, la quantità di osso compatto e spugnoso non variava significativamente nelle mandibole dei ratti gonadectomizzati, trattati farmacologicamente o meno, rispetto ai controlli. Solo il mascellare delle femmine ovariectomizzate presentava una porosità superiore, non diminuita dal trattamento con estrogeni. Questi risultati indicano che, contrariamente all'uomo, l'induzione di osteopenia sistemica mediante gonadectomia, a causa delle elevate sollecitazioni meccaniche gravanti sulle ossa del cavo orale, non è sufficiente a produrre nel ratto una consistente perdita di osso orale ma ad essa occorre associare un adeguato scarico meccanico della mandibola o del mascellare.Osteoporosis is a major public health problem, responsible for a great number of fractures, associated with devastating costs to society. In addition, oral bone loss has an enormous impact on the health quality of life of patients, affecting up to 90% of elderly individuals. The aim of this work was to elaborate an animal model of mandibular and maxillary osteoporosis in which to evaluate bone loss and possible prevention by pharmacological treatment. Six Sprague-Dawley rats were gonadectomized and treated with clodronate (male) or 17 beta-estradiol (female) for two months. Six gonadectomized and six sham-operated rats of both sexes were treated with placebo. The mandible and maxilla, fixed and methacrylate embedded, were serially sectioned, microradiographed and processed for histomorphometric analysis. Gonadectomy did not modify the amount of compact and trabecular bone in mandibles of rats of either sex, treated or not with clodronate or estrogens, compared to sham-operated rats. Compared to sham-operated rats, a 10-25% increase of bone porosity was found in the maxilla of ovariectomized rats, either receiving estrogens or not, while in male rats no difference among groups could be evidenced. The conclusion is drawn that rats, due to their peculiar masticatory habits yielding huge loads on oral bones, do not represent a suitable experimental model for studying oral bone loss related to skeletal osteoporosis. In order to worsen oral osteopenia it would be mandatory to combine gonadectomy with a mechanical unloading (i.e. after molar extraction) of mandibular or maxillary bone.

1999 - Le fratture intracorticali del metacarpeo III nel cavallo sportivo: dimostrazione sperimentale della validità dell’osteostissi [Relazione in Atti di Convegno]
P., Botti; Cavani, Francesco; Zaffe, Davide; M., Botti; Canè, Valerio
abstract

Studio quantitativo sulla riparazione di fori transcorticali e intracorticali nel metacarpo equino.

1999 - Mezzi di osteosintesi per FIR: metallosi dei tessuti perimplantari. [Abstract in Atti di Convegno]
Bertoldi, Carlo; Zaffe, Davide; Chiarini, Luigi; Tanza, D.; Consolo, Ugo
abstract

Placche per osteosintesi e tessuti circostanti sono stati studiati al fine di individuare la reale entità dei depositi metallici e le loro influenze sulle caratteristiche tissutali dal punto di vista patologico. Le placche, dopo 1÷9 anni di permanenza in sede, sono state espiantate da 8 pazienti (M/F, età 16÷38) il cui grado di flogosità locale era piuttosto elevato in 2 ed apprezzabile negli altri. Il tessuto osseo veniva incluso in Metacrilato, ottenute sezioni sottili per l’analisi istologica, mentre sia una sezione spessa (dopo dissolvimento superficiale del metacrilato) che le placche (in titanio o acciaio) con i tessuti aderenti (criosostituiti con CPD) venivano utilizzati per lo studio al SEM e microsonda a raggi X (EDS system). Nei pazienti a basso grado di flogosi, particelle di Ti erano evidenziabili solamente nei tessuti molli perimplantari. Nei due pazienti ad alto grado di flogosi, invece, in un caso si riscontravano cospicui depositi di Ti in cavità vascolari dell’osso, ma non nel tessuto calcificato; nell’altro, l’unico portatore di placca in acciaio, presenze di Fe e Cr ma non di Ni si riscontravano nel tessuto molle in contatto con l’acciaio, mentre in vicinanza di esso molti aggregati metallici, contenenti numerosi elementi, erano presenti in posizione perivascolare in una grossa cavità ossea. In conclusione, i risultati dimostrano una diretta relazione tra reattività patologica e le caratteristiche del mezzo di osteosintesi che, se inadeguate, sono la causa di una cospicua metallosi. Di particolare interesse clinico, poi, appare la distribuzione tissutale dell'Al (metallo sulla cui tossicità restano molti meno dubbi), che risulta contenuto sempre e comunque nelle viti per placche in lega di Ti esaminate e che presenterebbe una certa facilità alla diffusione ed alla fissazione nella lamine dense (acellulari-ipocalcifiche) degli osteoni. Codice: IT\ICCU\BVE\0164941

1999 - Neovascularized bone grafts: experimental investigation [Articolo su rivista]
Busa, R.; Adani, R.; Castagnetti, C.; Zaffe, Davide; Mingione, Antonio
abstract

Vascularized bone grafts are standardized procedures in reconstructive surgery but there are some disadvantages: donor site morbidity, limited number of natural donor sites, and complex technique. In this study, we test the possibility of creating a neovascularized bone graft utilizing a vascular implantation procedure in a rabbit model. Sixteen New Zealand adult white rabbits were used. In each animal, two iliac crest bone grafts (7 x 7 x 10 mm) were harvested. Vascular implantation of the right superficial femoral Vessels was performed in one of the two grafts, which was wrapped in a silicone envelope to avoid neovascularization from the surrounding tissues and positioned in a subcutaneous pocket in the right medial thigh. On the left side, the bone block, wrapped in the silicone envelope, was buried subcutaneously without vascular implantation. The operated animals were divided into two groups: Group I included eight rabbits explanted 4 weeks postoperatively and Group II included eight rabbits explanted 8 weeks postoperatively. Tetracycline injection was performed 72 hours preexplantation to evaluate new bone formation. Selective colloidal ink injection in the axial artery was performed to investigate the neovascularization before inclusion in poly-methyl-methacrylate (PMMA). Histological examination was performed in all explanted specimens comparatively. Histological examination 8 weeks after surgery showed a marked neovascularization, with normal bone cells. Tetracycline labeling showed new bone formation with a normal pattern. In ail nonvascularized specimens, no viable cells or neovascularization and no bone formation were found. The vascular implantation procedure can induce a good neovascularization with new bone formation in a small bone graft. The possibility of neovascularization induction by the simple vascular implantation procedure has several clinical implications in reconstructive surgery.

1999 - Osteocyte-osteoclast morphological and putative functional relationships [Abstract in Rivista]
Palumbo, Carla; Ferretti, Marzia; Zaffe, Davide; Marotti, Gastone
abstract

Osteocytes could intervene in the process of bone resorption.

1999 - Presenza di elementi metallici nei tessuti circondanti mezzi di osteosintesi per FIR. [Abstract in Rivista]
Zaffe, Davide; Bertoldi, Carlo; Consolo, Ugo
abstract

Al fine di individuare la presenza di elementi metallici e le loro influenze sulle caratteristiche tissutali, sono state analizzate sia placche per osteosintesi che i tessuti circostanti. Le placche sono state espiantate da otto pazienti (M/F, età 16*38) dopo essere rimaste "in situ" da 1 a 9 anni. Il tessuto osseo veniva incluso in metacrilato, ottenute sezioni sottili per analisi istologiche, mentre sezioni spesse (dopo dissolvimento del metacrilato superficiale) che le placche (in Ti o acciaio) con i tessuti aderenti (criosostituiti con CPD) venivano utilizzati per lo studio al SEM e microsonda a raggi X (EDS system). L'analisi clinica evidenziava che il grado di flogosità locale era piuttosto elevato in 2 pazienti ed era apprezzabile negli altri. Presenza di Ti era apprezzabile, particolarmente, nei tessuti molli peri-implantari dei pazienti a basso grado di flogosi. Cospicui depositi di Ti erano evidenziabili in un paziente con alto grado di flogosi, in cavità vascolari dell'osso e, solo in parte, nel tessuto calcificato. Al contrario, l'Al, presente in piccola quantità nella composizione delle placche e, soprattutto delle viti, è stato riscontrato non solamente nei tessuti molli ma anche nell'osso lamellare, cioè nell'osso formato più tardivamente attorno alla placca. Nell'altro paziente ad alto grado di flogosi, l'unico sul quale era stata utilizzata una placca in acciaio, nel tessuto molle, in contatto con il metallo, si riscontravano presenza di Fe e Cr ma non di Ni. In una grossa cavità ossea, posta in prossimità della placca, erano presenti in siti perivascolari molti aggregati metallici contenenti numerosi elementi. In conclusione, i risultati evidenziano una stretta relazione tra reattività patologica e le caratteristiche del mezzo di osteosintesi che sono la causa di una cospicua metallosi , quando i materiali di cui sono formati i mezzi posseggono le adeguate caratteristiche, come nei casi indagati.

1999 - Tavole di Istopatologia del cavo orale: I - Tipologia degli epiteli di rivestimento. Seconda parte – Organi del cavo orale e strutture molli. [Articolo su rivista]
Zaffe, Davide; A. R., Botticelli
abstract

No riassunto

1999 - Tavole di Istopatologia del cavo orale: I - Tipologia degli epiteli di rivestimento. Terza parte – Epitelio pavimentoso pluristratificato non cheratinizzato paracheratosico EPPP. [Articolo su rivista]
Zaffe, Davide; A. R., Botticelli
abstract

No riassunto

1999 - Tavole di Istopatologia del cavo orale: II - Tipologia degli epiteli ghiandolari. Prima parte – Caratteristiche morfofunzionali delle ghiandole salivari. [Articolo su rivista]
Zaffe, Davide; A. R., Botticelli
abstract

No riassunto

1999 - Tavole di Istopatologia del cavo orale: II - Tipologia degli epiteli ghiandolari. Prima parte Ghiandole sottomandibolare e sottolinguale. [Articolo su rivista]
Zaffe, Davide; A. R., Botticelli
abstract

No riassunto

1998 - A reabsorbable tubular chamber for the treatment of large diaphyseal bone defects. Experimental study in rabbits. [Articolo su rivista]
R., Giardino; M., Fini; Aldini, N. N.; G., Giavaresi; M., Rocca; L., Martini; Zaffe, Davide; Canè, Valerio
abstract

Twenty-five rabbits were used to test the healing of diaphyseal defects by means of a reabsorbable tubular chamber In 20 animals a 10 mm gap was created in the left radius and bridged with a poly-L-lactide chamber (experimental side). The same defect was created on the right radius, remaining untreated (control side). In the remaining 5 animals, the right radius was left intact and they were used only for biomechanical tests at 12 months. X-rays and histomorphometry showed no bone repair at the control side while the inner surface of the chamber was progressively lined by neoformed bone (75% of the normal cortical thickness). Biomechanical data demonstrated that elastic modulus and ultimate stress were not significantly different in both experimental and intact radii. The chamber, by preventing the passage of soft tissues and creating a dose space for intrinsic repair factors, seems to be a suitable device for the repair of long bone defects.

1998 - Immunohistochemical detection of cell-cycle associated markers on paraffin embedded and formalin fixed needle biopsies of prostate cancer: correlation of p120 protein expression with AgNOR, PCNA/Cyclin, KI-67/MIB1 proliferation-scores and Gleason gradings. [Articolo su rivista]
Botticelli, A. R.; Casali, A. M.; Botticelli, L.; Zaffe, Davide
abstract

Paraffin embedded and formalin fixed needle biopsies of prostate cancer (PC) were used to immunocytochemically detect the p120 nucleolar protein in relation to the Gleason histological gradings (GHG), the labelling indices of proliferating nuclear immunocytochemical markers (PCNA/Cyclin, Ki-67/MIB1) and the argyrophilic nucleolar region (AgNOR) rate. The twenty-six cases of PC (6 from large histological samples and 20 from needle biopsies) were equally distributed into low (less than or equal to 6) or high (greater than or equal to 7) GHG groups. The p120 nucleolar protein immunocytochemical reaction was randomly expressed in large histological sections but uniformly distributed without gaps in needle biopsy sections. Only on the latter were quantitative values of PCNA/Cyclin (23.2 in low and 45.3 in high GHG), Ki-67/MIB1 (13.8 in low and 43.3 in high GHG) and AgNOR (5.0 in low and 7.5 in high GHG) related to those of p120 nucleolar protein (0.8 in low and 3.8 in high GHG). The values of all these cell cycle markers increased from low to high GHG of PC, all four reaching high statistical significance between the two groups (ANOVA - two tailed p &lt; 0.0001). The PCNA/Cyclin index showed a higher positivity than the Ki-67/MIB1 index in PC with low GHG but not in PC with high GHG. In conclusion, paraffin embedded and formalin fixed PC needle biopsies exhibit a higher diagnostic PCNA/Cyclin than Ki-67/MIB1 index for cases presenting differentiated features, whereas p120 nucleolar protein detection seems to be a suitable marker of poorer outcome of PC.

1998 - Innesti ossei neovascolarizzati. Studio sperimentale preliminare. [Articolo su rivista]
R., Busa; R., Adani; C., Castagnetti; Zaffe, Davide; Mingione, Antonio
abstract

Gli innesti ossei vascolarizzati sono oggi procedure standardizzate in chirurgia ricostruttiva ma presentano alcuni svantaggi: la morbidità del sito donatore, il numero limitato di zone donatrici "naturali", la tecnica complessa. La neo-angiogenesi è un fenomeno di comune osservazione nei processi riparativi e proliferativi dei tessuti. Nel presente studio abbiamo voluto testare la possibilità di creare un innesto osseo "neo-vascolarizzato" utilizzando una procedura di impianto vascolare nel tessuto osseo del coniglio. Lo studio è stato condotto su 16 conigli New Zealand adulti. Il prelievo di due frammenti ossei di dimensioni mm 10x7x7 è stato effettuato a livello delle ali iliache di ogni animale. L'impianto del peduncolo vascolare femorale superficiale è stato effettuato in uno dei due frammenti. Il frammento sottoposto ad impianto vascolare è stato avvolto in un involucro di silicone e posizionato in una tasca sottocutanea a livello della coscia destra. Sul lato sinistro il secondo frammento è stato invece avvolto nel foglietto di silicone e posizionato in sede sottocutanea senza eseguire impianto vascolare. Abbiamo suddiviso gli animali in due gruppi di 8 unità ciascuno: nel gruppo I l'espianto è avvenuto dopo 4 settimane, nel gruppo II a otto settimane. Lo studio è stato condotto mediante iniezione di tetraciclina 72h prima dell'espianto per valutare la deposizione di nuovo tessuto osseo. Per studiare la neo-vascolarizzazione, in alcuni frammenti di ciascun gruppo è stata effettuata iniezione di inchiostro colloidale (mediante cateterizzazione dell'arteria centrale) prima della inclusione in PMMA. Lo studio istologico ha dimostrato nei frammenti a 8 settimane, la formazione di una ricca rete di vasi neoformati con cellule ossee paragonabili a quelle del tessuto normale. Anche la marcatura con tetraciclina ha evidenziato un migliore trofismo osseo a 8 settimane con deposizione ossea di aspetto normale. I frammenti non vascolarizzati hanno dimostrato assenza di segni diretti ed indiretti di "vitalità" cellulare e tessutale dell'osso. La procedura di impianto vascolare si è dimostrata in grado di indurre neo-vascolarizzazione e neo-deposizione ossea in un piccolo frammento osseo. Questo modello è semplice, ripetibile ed interessante da un punto di vista biologico e riteniamo che possa avere utili ripercussioni in campo clinico ortopedico.

1998 - Kieferorthopädische behandlung und pulsierende elektromagnetische felder [Articolo su rivista]
D., Fraticelli; P., Gandini; M. F., Sfondrini; A. R., Botticelli; Zaffe, Davide
abstract

Es wurde ein Experiment an Kaninchen durchgeführt, das klären solite, ob PEMF in der Lage wären, die Zahnverschiebung und die Knochenregeneration zu erleichtern. Dazu wurden 9 männliche Kaninchen der Rasse New Zealand ausgewählt, die auf der linken Seite nur mit orthodontischen Kràften, auf der rechten Seite mit orthodontischen Kràften und PEMF behandelt wurden. Die Resultate zeigen, daB die PEMF mit einer relevanten statistischen Signifikanz einen positiven Effekt auf die Verschiebung von Zähnen haben. Die histologische Untersuchung hat bei den Unterkieferhälften, die zusätzlich mit PEMF behandelt wurden, eine deutlich stärkere Aktivität der Osteoblasten ergeben. Uberdies war auch die Qualität des Knochengewebes hier besser als in den Unterkieferhälften, die nur mit orthodontischen Kräften behandelt wurden.

1998 - Morphology of perimplant regenerated bone, in sheep’s tibia, by means of guided tissue regeneration. [Articolo su rivista]
R. Rodriguez y., Baena; Zaffe, Davide; U. E., Pazzaglia; S., Rizzo
abstract

No data on the resistance to functional loads of bone regenerated by means of guided tissue regeneration, can be found. In this paper the new-formed bone is analyzed, in cases that see the surgical creation of defects in testing animals. The morphological aspects of perimplant bone, regenerated by means of bone substitutes or not, were evaluated. A coronal defect was created by means of a counter-sink bur. The following step provided for osseointegrated fixtures, with a machined or blasted (TiOblast) surface, to be installed. Some bone defects were filled with Bio-Oss®, and covered with resorb-able membrane (Vycril®), others were left unfilled. The animals were sacrificed after different periods of time (24 and 45 days). Some thick sections (200 µm) underwent then microradiography and were examined with a microscope, under transmitted and polarized light. Other sections, thin (5 µm), were coloured with toluidine blue, Gomori's Stain and Soloch-rome Cyanine/Congo red. Data confirm the excellent behaviour of bovine bone and of TiO blasted fixtures. The experimental results bring into evidence that, in cases of Guided Bone Regeneration (GBR) by means of membrane, the use of fixtures with a blasted surface (TiOblast), and of Bio-Oss® as bone substitute, made osseointegration easier. Results, moreover, suggest that in case of implant surgery with GBR, in order to allow the maturation of regenerated bone, it's healing time must be prolonged.

1998 - Rabbit bone behavior after orthodontic and pulsed low-frequency electromagnetic field treatments [Articolo su rivista]
Zaffe, Davide; Fraticelli, D.; Sfondrini, Mf; Caielli, D.; Botticelli, Ar
abstract

The effect of low-frequency pulsed electromagnetic fields (PEMF) on bone was studied after an orthodontic treatment. A spring was positioned between the incisors and the first molar on both sides of the rabbit mandible for 14 days. A PEMF treatment was performed 6 h/day on the right side only. A greater distance between the first and the second molar was recorded in the PEMF treated side with respect to the left side. In addition, analysis of undecalcified sections shows a lower number and width of erosion cavities and a greater amount of newly formed (fluorescent) bone on the right side. In conclusion, PEMF treatment not only appears to increase bone formation, as previously reported in the literature, but, acting on osteoclast activity, also seems to improve bone quality during orthodontic treatment.

1998 - Tavole di Istopatologia del cavo orale: I - Tipologia degli epiteli di rivestimento. [Articolo su rivista]
Zaffe, Davide; A. R., Botticelli
abstract

No riassunto

1998 - Tratamiento ortodóncico y campos electromagnéticos pulsantes [Articolo su rivista]
D., Fraticelli; P., Gandini; M. F., Sfondrini; A. R., Botticelli; Zaffe, Davide
abstract

El objetivo de este estudio era analizar los efectos de los campos electromagnéticos pulsantes (CEMP) sobre el desplazamiento dentario y el comportamiento óseo. El estudio se llevó a cabo sobre 9 machos de conejo de Nueva Zelanda, de 3,2 kg de peso. Se colocó un muelle de Sentalloy®, que producía 25 g de fuerza, entre el incisivo inferior y el primer molar en ambos lados de la mandíbula. En todos los animales se realizó un tratamiento ortodoncico de 14 dias. En el lado derecho se aplicó un campo electromagnetico de baja frecuencia durante 6 horas al día, siempre a la misma hora. Se registró un efecto facilitador del movimiento dentario por el CEMP y se observaron patrones histólogicos diferentes en el lado izquierdo y en el derecho: se encontro un aumento de la actividad osteoblastica y una mejor calidad de hueso en el lado sometido a los CEMP.The aim of this study was to analize the effects produced by Pulsating Electromagnetic Fields (PEMF) both on dental displacement and on bone behaviour. The study was carried out on 9 New Zealand male rabbits, 3.2 kg in weight. In both the left and the right side of the mandible a Sentalloy® coil spring, producing a force of 25 g was attached between the lower incisor and the first molar. The orthodontic treatment was performed in all animals for 14 days. The right side of the mandible received a low frequency pulsed electromagnetic field treatment for 6 hours per day, always at the same time of day. A facilitating effect of the PEMF on tooth displacement was recorded and different histologic patterns were observed in the left and in the right sides: an increased osteoblastic activity and a better quality bone were found in PEMF-treated mandibles.

1998 - Trattamento ortodontico e campi elettromagnetici pulsanti. [Articolo su rivista]
D., Fraticelli; P., Gandini; M. F., Sfondrini; A. R., Botticelli; Zaffe, Davide
abstract

È stato condotto un lavoro sperimentale sul coniglio al fine di confermare se i campi elettromagnetici pulsanti (CEMP) siano in grado di determinare un effetto facilitante negli spostamenti dentali e sulla rigenerazione ossea. Per questo scopo sono stati selezionati 9 conigli maschi di razza New Zealand, trattati con sole forze ortodontiche (emimandibola sinistra) e con forze associate a irradiazione con CEMP (emimandibola destra). I dati sperimentali hanno confermato la presenza di effetti positivi dei CEMP sugli spostamenti dentali con una significatività statistica rilevante. L'analisi istologica ha rilevato che i campioni di mandibole di coniglio trattati con i CEMP presentano un'attività osteoblastica più marcata rispetto ai non trattati ed una qualità di tessuto osseo migliore.

1997 - Analisi comparativa di materiali diversi utilizzati in GBR associata all’implantologia [Articolo su rivista]
G. C., Leghissa; A., Botticelli; Zaffe, Davide; S., Moretti
abstract

L'uso della rigenerazione ossea guidata (GBR), associata all'implantologia, è diventato patrimonio della moderna chinirgia odontoiatrica. Molte ricerche istologiche e la comprovata evidenza clinica sono concordi nel dimostrare la validità di questa procedura. La capacità rigenerativa dipende dalla presenza delle cellule totipotenti, provenienti dal coagulo di origine ossea, in grado di maturare, differenziarsi e moltiplicarsi apponendo nuovo osso fino al riempimento del difetto stesso. Tale guarigione può avvenire solo a condizione che lo spazio sia mantenuto nel tempo, permettendo così alla membrana semipermeabile di svolgere appieno il ruolo di «tenda» isolante degli stipiti cellulari indesiderati (epitelio). Le attenzioni dei ricercatori si sono oggi concentrate sui problemi di perfezionamento della metodica, cercando di capire se e quanto il grado di rigenerazione ossea può essere influenzata dai materiali che si utilizzano. Vi sono differenze impiegando membrane riassorbibili o non riassorbibili? Quali tipi di membrana? Quale riempitivo? Sintetico, di derivazione naturale o nulla? Con questo lavoro gli autori cercano di dare un contributo alla soluzione di questi quesiti, analizzando sul piano clinico e istologico otto siti chirurgici trattati con le metodiche della GBR associata all'implantologia.

1997 - Materiali osteoconduttori: sperimentazione animale e analisi strumentali. Nota II [Articolo su rivista]
Baena, R. Rodriguez y; Zaffe, Davide; Brusotti, C.; Marchetti, C.; Botticelli, A.; Rizzo, S.
abstract

Nella pratica chirurgica odontoiatrica, quando non si riesca a prelevare osso autogeno per riempire difetti ossei, si possono utilizzare materiali alloplastici che apparentemente danno buoni risultati in termini di osteorigenerazione. Nel presente lavoro è stato approfondito lo studio su cinque diversi materiali osteoconduttori utilizzati nella pratica chirurgica orale basandosi su analisi microradiografiche, esame al microscopio elettronico a scansione e la microanalisi a raggi X. In animali da esperimento (ratti) sono state create cavità ossee di circa 3 mm di diametro in entrambe le tibie: in un lato la cavità è stata riempita con i materiali da testare mentre dall'altro il difetto osseo è stato fatto guarire per vie naturali. Un'analisi approfondita dei risultati ottenuti con le suddette metodiche ha portato gli Autori alla conclusione che i materiali in esame possono essere considerati adatti agli scopi per i quali vengono commercializzati. I risultati ottenuti dimostrano però che i vantaggi in termini di guarigione sono minimi rispetto ai controlliIn daily dental surgery practice, when it is not possible to obtain enough autogenous bone graft to fill bone defects, bone substitutes can be useful for bone regeneration. After a preliminary microscopic examination of histologic samples obtained from semithin sections of the tibias of rats showing no major differences in the results both for the single material and implant time, further studies on five different osteoconductive materials used in oral clinical practice were carried out with microradiography, SEM and X-ray microanalysis. In experimental animals (rats) bone defects 3 mm large were surgically induced in both tibias: one of the defects was filled by bone substitutes and on the other side the bone defect healed naturally. The findings obtained were studied in depth, and allowed to conclude that the materials tested are suitable for the purpose for which they are marketed. Non-demineralized bovine bone showed the best results with a high degree of osteointegration. However, the results also show that not all the materials tested offer healing advantages over controls.

1997 - Morphostructural relationships between bone and implant: Comparative analyses by optical microscopy and microradiography [Articolo su rivista]
Ae, Bianchi; G., Gallini; R., Fassina; F., Sanfilippo; Zaffe, Davide
abstract

This study assessed the relationship between the surfaces of a hollow cylindrical titanium implant and the consequent bone organization around it. A human bone maxillary specimen was taken that enclosed an implant which had lasted 28 months under prosthetic loading. The implant was removed because of fracture that prevented the implant from being used as a supporting element for new prosthetic aims. The bone block-section was fixed and embedded, several sections were obtained, and each section was analyzed using three different histologic analyses. optical microscopy under ordinary light and polarized light and microradiography. Comparative analyses were required on every single section to provide a complete morphostructural analysis of the peri-implant bone. Data retrieved by this research showed the presence of woven bone in the bone layer facing the external implant surface several months after ifs surgical fitting and functionalization. This finding demonstrates the importance of woven bone, first as holding sheath in the immediate postsurgical stage, and second as a mold for the subsequent centripetal accrementition of secondary lamellar bone.

1997 - Pulsed electromagnetic fields modulate enzymatic activity during the early stages of bone repair [Articolo su rivista]
Canè, Valerio; Zaffe, Davide; Cavani, Francesco; P., Botti; S., Soana
abstract

The goal of this study was to investigate whether PEMFs influence enzymatic activities during the early stages of bone repair. Two transcortical holes (4.5 mm diameter) were drilled at the same diaphyseal level in the lateral margin of the right and left metacarpal bone (McIII) of six adult male horses. The left McIII were exposed to PEMFs (75 Hz; 2.8 mT, 1.3 ms impulse width) 24 h/day; the right untreated McIII were used as controls. Horses were sacrificed 8 and 15 days after the operation. The bone segments containing the holes were fixed, dehydrated in ethanol solutions, and, undecalcified, embedded in methylmethacrylate. The midlongitudinal sections of the holes were either stained with soluidine blue or processed for evaluation of the total alkaline phosphatase (TRAP) and the tartrate-resistant acid phosphatase (TRAP). In PEMF-treated holes we found: (1) TALP is strongly positive with respect to the controls; (b) the newly formed bony trabeculae are more abundant than in the controls; (c) in both treated and control holes, no TRAP-positive osteoclasts were observed on the hole surface, whereas several osteoclasts were located on the newly formed bone tracebulae. On the basis of these data, it may be concluded that PEMFs accelerate the healing process of transcortical holes and enhance the enzymatic activity of repair tissue.

1996 - Histomorphological and chemico-physical analyses of the mineral matrix of micropetrotic human bone [Articolo su rivista]
Remaggi, Francesca; Ferretti, Marzia; Canè, Valerio; Zaffe, Davide
abstract

Micropetrotic areas of human bone were analyzed with reference to their distance from blood vessels and to the age of the subjects. Undecalcified bone sections were treated with various solvent, soaking and etching substances to establish the nature of the material occluding the osteocytic canalicular cavities, and were examined by means of microradiographic and microdurimetric methods and X-ray microanalysis to evaluate the degree of mineralization in the bone matrix. Since it was only after strong etching with HCl that the canalicular network became visible under light and scanning electron microscopy, it is clear that the debris filling the-canalicular network consists almost entirely of mineral substance. The degree of mineralization of micropetrotic bone is high because it is always a more mature type Of bone, but the mineral content of the matrix and the Ca/P ratio do not differ significantly from those of neighbouring bone where the canalicular network is fully pervious.

1995 - Analisi clinico-morfologica della GBR nel grande rialzo del seno mascellare [Articolo su rivista]
Zaffe, Davide; A., Botticelli; G. C., Leghissa; D., Di Stefano
abstract

È possibile affermare, data la ripetitività e sovrapponibilità dei quadri istologici osservati, che la presenza, o l'assenza, della membrana semipermeabile all'esterno della breccia vestibolare sembra condizionare decisamente in senso positivo la maturazione di nuovo osso, nei casi di grande rialzo del seno, contribuendo a un più rapido e più completo riassorbimento del materiale di riempimentoThis article analyzes six cases of bone regeneration of the maxillary sinus with positining of implants: core samples of bone were taken from the newly-formed areas of the second surgical procedure for the prosthesic connection of implants. In the three cases where membranes were positioned, the ossifìcation was found to be more complete and more mature.

1995 - Coral granules in the repair of human mandibular defects [Capitolo/Saggio]
Zaffe, Davide; Palumbo, Carla; E., Cantoni
abstract

Book with contributes of studies on biomaterials

1995 - Morphometric study of collagen maturation in chick compact bone [Articolo su rivista]
Palumbo, Carla; Ferretti, Marzia; Palazzini, Silvana; Zaffe, Davide
abstract

An ultrastructural-morphometric study was carried out on the process of osteoid maturation in growing surfaces of parallel-fibered chick bone. The aim was to investigate the distribution, size and amount of collagen fibrils (CFs), as well as the proteoglycan (PG) content, throughout the osteoid seam and in the adjacent bone. The results show that the organic components secreted by osteoblasts undergo complete maturation inside the osteoid seam only. Proceeding from the secreting plasma membrane of osteoblasts (osteoidogenic surface) towards the mineralizing surface, we found that CFs gradually increase in diameter but not in number per surface unit. As a consequence, the proportion of osteoid seam occupied by CF increases too, at the expense of the interfibrillar substance. PG content also decreases inversely in this direction. In the adjacent bone, CF size and density do not change significantly with respect to the mature osteoid close to the mineralizing surface.

1995 - Spostamento ortodontico del primo molare superiore di ratto: studio istomorfologico dell’osso alveolare [Articolo su rivista]
C., Verna; Zaffe, Davide
abstract

È stata esaminata la struttura dell'osso alveolare adiacente sia al primo molare superiore sottoposto a spostamento ortodontico che ai denti contigui in 55 ratti Wistar maschi dell'età di 3 e 10 mesi, il movimento è stato ottenuto applicando una molla chiusa di Sentalloy da 50 cN tra il primo molare superiore sinistro e gli incisivi superiori. Ai ratti veniva somministrata tetraciclina per via sottocutanea (50 mg/kg) 48 ore prima del sacrificio dopo i tempi sperimentali di 4, 7, 11 e 14 giorni. I segmenti ossei mascellari venivano fissati in parafolmaldeide tamponata (0,1 M, pH 7,2) per 4 ore e inclusi in metilmetacrilato. Sono state eseguite sezioni trasversali a livello coronale, medio e apicale delle radici dentarie mediante un microtomo a lama circolare diamantata . Le sezioni spesse (100-120 µm), lucidate con carta abrasiva e allumina, sono state microradiografate e analizzate al microscopio a luce ordinaria e fluorescente. Le sezioni sottili (5 µm) sono state colorate con Blu di Toluidina e trattate istochimicamente per TRAP. È stato osservato un cospicuo riassorbimento osteoclastico dell'osso alveolare attorno al dente spostato ortodonticamente e a quelli adiacenti, sia dal lato di tensione che dal lato di compressione. In quest'ultimo è stata osservata anche neodeposizione ossea, ma solo dopo lunghi periodi di trattamento. Una cospicua deposizione ossea, più marcata con l'aumentare dei tempi di trattamento, è stata osservata frequentemente nel versante vestibolare dell'osso alveolare. Non è stata osservata alcuna relazione tra il comportamento dell'osso e l'età dei ratti. In conclusione, questi risultati preliminari indicano che al movimento ortodontico consegue un diffuso riassorbimento osseo, senza relazione con forze di tensione o di compressione. Sembra dunque che il movimento ortodontico abbia luogo in un contesto di globale adattamento scheletrico: assieme ad aree di notevole erosione ossea è possibile osservare nuove aree di deposizione tendenti a ripristinare la stabilità meccanica.

1994 - A comparative study of the effectiveness of e-PTFE membranes with and without early exposure during the healing period. [Articolo su rivista]
M., Simion; M., Baldoni; P., Rossi; Zaffe, Davide
abstract

This study compared clinical, microbiologic, and morphostructural aspects of the healing process in clinical cases treated with expanded polytetrafluoroethylene membranes placed in fresh extraction sockets, which did or did not show early membrane exposure. The examination was focused particularly on morphology of the microbic population and its ability to penetrate membrane pores. Results of the study suggest that use of the membranes is effective in the treatment of fresh extraction sockets with osseointegrated implants; that the membranes are highly biocompatible with gingival tissues; and that early exposure of the membranes during healing hinders the effectiveness of guided tissue regeneration in periimplant tissues.

1994 - Histomorphological analysis of the effect of rigid fixation on growing sutures in the rabbit [Articolo su rivista]
A., Carinci; Zaffe, Davide; A., Pagliarini; L., Clauser; G., Calura; Marotti, Gastone; C., Curioni
abstract

The effect of internal rigid fixation (IRF) on bone growth was studied in an experimental model set up in the rabbit. The frontonasal suture of the right side was surgically bridged by a microplate. As reference for bone growth, four screws were placed symmetrically in the four bony segments including the frontonasal suture on both sides. The suture development was followed dynamically for 40 days on the basis of the position of the screws established radiographically. The rate of bone formation along the sutural bones was evaluated by means of the tetracycline labelling technique. The structure of the newly formed bone and its degree of mineralization were respectively analysed under polarized light and with microradiography. It was demonstrated that IRF prevents growth of the sutural membrane but not of the osteogenic process; as a consequence the constrained sutures soon undergo synostosis. This fact must be taken into consideration when IRF is employed in children in order to avoid delayed removal of the plate irreversibly stopping the growth of the constrained suture.

1994 - The microscopic determinants of bone mechanical properties [Articolo su rivista]
Marotti, Gastone; Muglia, Maria Antonietta; Palumbo, Carla; Zaffe, Davide
abstract

Composition and structure of the bone matrix, i.e. the bony substance surrounding osteocyte microcavities, was considered in the Light of their mechanical implications. A novel classification of bone tissues was proposed, on the basis of recent comparative studies on collagen fiber texture and osteocyte lacunae distribution, performed under polarized light, scanning and transmission electron microscopies. In particular, contrary to the classical view, lamellar bone can no longer be considered a variety of parallel-fibred bone since bony lamellae are not made up of parallely arranged collagen fibers, but of highly interlaced fibers, the lamellation being due to the alternation of acellular collagen-rich and cellular collagen-poor layers, namely of dense and loose lamellae, respectively. It is postulated that the deposition of woven- and lamellar-bone depends on the manner of recruitment of the osteocyte-differentiating osteoblasts from the osteogenic laminae and not on the spatial orientation by osteoblasts of collagen fibers. The possible role played by osteocyte as mechanical sensor in selecting the type of bone tissue laid down on bone surfaces is discussed.

1993 - In vivo behaviour of a high performance duplex stainless steel [Articolo su rivista]
A., Cigada; G., De Sanctis; Gatti, Antonietta; A., Roos; Zaffe, Davide
abstract

An in vivo investigation of a new high molybdenum and nitrogen duplex stainless steel (25Cr-7Ni-4Mo-0.3N) has been performed. Cylindrical pins and specially developed devices, to test in static conditions the in vivo localized corrosion resistance, made of this new duplex steel and of a common austenitic stainless steel were implanted in rabbit's femurs for 6 and 12 months. After sacrifice, SEM observations and EDS microanalyses to detect metallic ion release were carried out on the femur sections surrounding the pins. Morphologic observations with stereoscope and SEM were performed on the metallic surfaces of the special devices in order to detect the presence of localized corrosion. Both ion release and localized corrosion were observed for the specimens made of austenitic stainless steel, but not for those made of 25Cr-7Ni-4Mo-0.3N duplex stainless steel.

1993 - Osteoconduzione del Fosfato Tricalcico e del Corallo [Articolo su rivista]
Zaffe, Davide; Ferretti, Marzia; E., Cantoni; M., Tassinari
abstract

Granuli di Fosfato Tricalcico (TCP) o di Corallo madreporico sono stali impiantati in cavità post-estrallive di 14 Uomini adulti; dopo 3-75 mesi, in dascun soggetto è stata effettuata una biopsia, poi fissata in paraformaldeide e inclusa in PMMA, e quindi trattata per il microscopio ottico, SEM e microsonda a raggi-X. I risultati dimostrano che tra i granuli di Corallo l'osso neoformato è già presente dopo 3 mesi, mentre tra i granuli di TCP non compare prima di 6 mesi. I granuli di Corallo scompaiono dalle biopsie dopo 10-12 mesi, mentre granuli di TCP hanno dimensioni simili a quelle iniziali anche dopo 15 mesi di impianto. L'osso neodeposto, inoltre, viene assai più estesamente a diretto contatto con il Corallo che con i granuli di TCP. La microsonda ai raggi-X dimostra infine che l'osso a ridosso del Corallo ha un contenuto minerale più elevato. La neodeposizione avviene pertanto in tempi più brevi e con migliori modalità negli impianti di Corallo rispetto a quelli di TCP; la più elevala capacità riparatrice di difelli ossei mostrata dal Corallo è verosimilmente da attribuire alla maggiore reattività del Carbonato di Calcio rispetto a quella del Fosfato.The alveolar cavities, obtained after the removal of a toolh in 14 adult men, were filled with TriCalcium Phosphate (TCP) or Coral; from 3 to 75 months after the implant, a biopsy was made and processed for optical microscope, SEM and X-ray microanalysis. The results show that bone tissue is present among the Coral granules after 3 months, whereas around TCP granules bone does not appear before 6 months; Coral granules disappear from biopsies after 10-12 months, whereas TCP granules have the same size as at the start even after 75 months; there is direct bone-Coral contact but only a partial bone-TCP contact. X-ray microanalyses show that the bone mineralization is higher close to the Coral than near the TCP. In conclusion, the new bone formation appears to take place at a higher rate in Coral implants than in TCP ones; the higher capability shown by Coral in bone defect repair is probably due lo the higher reactivity of Calcium Carbonate with respect to Calcium Phosphate.

1993 - Study on short-term implants of a fluorinated glass in bone [Articolo su rivista]
Zaffe, Davide; A., Krajewski; A., Ravaglioli; S., Contoli
abstract

The behaviour of a proposed fluorinated glass implanted in femurs of rabbits for a short time was studied on contact microradiographs by electron microscopy and X-ray microprobe. The glass appeared to be surrounded by several bony trabeculae starting from the endosteal surface; some trabeculae were in contact with the outer part of the glass, X-ray analysis showed that degradation occurs in the outer layer only, although without uniformity. Si-rich zones were randomly located in the deeper part of the layer that externally formed zones with P and Ca content higher than that in the non-implanted glass.

1992 - Bioactive glass as a bone substitute [Capitolo/Saggio]
O. H., Andersson; K. H., Karlsson; Gatti, Antonietta; Zaffe, Davide; J., Miettinen; A., Yli Urpo
abstract

The bone-bonding ability as well as the osteconductivity of a bioactive glass was studied. It was established by mechanical testing that bone bonds firmly to the glass within two months in rabbit tibia. During a 3-month implantation period in sheep it was found that cylinders were well integrated in the femur. However, empty control holes were also filled with new bone. In contrast, in the sheep mandibular jaw new bone did not fill holes which were left empty. Holes filled with granules, however, were almost completely filled with new bone. Thus, in addition to its bone-bonding ability, the studied glass also conducts bone growth along its surfaces, i.e. is osteoconductive.

1992 - Bioactive glasses and chemical bond [Capitolo/Saggio]
Gatti, Antonietta; Zaffe, Davide
abstract

Bioactive materials are investigated for their "osteoconductive" activity. After an analysis of the chemical bond that occurs between the material and the bone in function of the studies carried out in the past ten years, new considerations on the ions diffusing from the implant toward the bone are reported. The results of the research on three diferent types of glasses in granular form implanted in sheep's mandibular pockets are presented. Phenomena of diffusion are seen in all the materials, not only from the material, but also toward the material. In one material the entranced potassium, that is not present in its composition was observed.

1992 - Bioceramics in orthopedic surgery: know how status and preliminary results [Relazione in Atti di Convegno]
S., Giannini; A., Moroni; Coppola, G.; Ponziani, L.; A., Ravaglioli; A., Krajewski; A., Venturini; Pigato, M.; Zaffe, Davide
abstract

Bioceramic materials for orthopaedic surgery can be distinguished in two groups: bioinert and bioactive ceramics. The bioinert ceramics provoke a minimal tessutal reaction; the bioactive ones stimulate the bone ingrowth and a bone-material link capable to support physiological loads occurs. Alumina (Al2O3) is an inert bioceramic which presents an excellent mechanical strenght and a very low wear. For this reason Al2O3 is used in manufacturing of acetabular component and femoral head of total.hip.arthroplasties (THA) Al2O3 is also used as coating of metallic hip prosthetic stems and for small joint prostheses. As bioactive ceramics we analyzed bioglass and hydroxyapatite (HA). Bioglasses are actually considered very promising materials but they have not still a clinical application. HA is the more used bioactive material in orthopaedics. The close interface link with bone tissue allows the use of HA in bone cavities filling of various skeletal diseases and as coating of metallic prostheses.

1992 - Comparison between the "in-vivo" behaviours of a new active glass used as block and granules in sheep [Relazione in Atti di Convegno]
Gatti, Antonietta; Zaffe, Davide; O. H., Andersson
abstract

A new bioactive glass was implanted in mandibular sheep's jaw as granules and as a block to check: a) the degradation of the material in the biological surrounding, b) its probable osteoconductivity, c) the setting-up of a chemical bond of the material with bone and d) the influence of the morphology on the material degradation and on the interface developed with bone. After a 3-month implantation, the sheep was sacrificed and the bone sections containing the materials were observed under a scanning electron microscope and an energy dispersion system in order to evaluate the morphology of the glass and the biodegradation.

1992 - Endosseous implants: the relevance of animal species, skeletal region and porosity of material [Relazione in Atti di Convegno]
Zaffe, Davide
abstract

No abstract

1992 - I bioceramici in chirurgia ortopedica: Stato dell’arte e risultati preliminari [Bioceramics in orthopaedic surgery: state of the art and preliminary results] [Articolo su rivista]
S., Giannini; A., Moroni; M., Pompili; F., Ceccarelli; S., Cantagalli; V., Pezzuto; L., Trinchese; Zaffe, Davide; A., Venturini; M., Pigato
abstract

I materiali ceramici utilizzabili in chinirgia ortopedica possono essere distinti in bioinerti, cioè tali da promuovere la minima reazione tissutale, e bioattivi, cioè capaci di stimolare la crescita del tessuto osseo, stabilendo con esso un legame in grado di sopportare carichi fisiologici. L'allumina è un ceramico bioinerte che, se dotato di appropriate caratteristiche strutturali, presenta un'ottima resistenza meccanica ed una bassissima usura. Per tali motivi viene utilizzata per la costruzione di componenti protesiche d'anca (testa e cotile), come rivestimento di steli protesici metallici e per la realizzazione di protesi per piccole articolazioni. Fra i ceramici bioattivi vengono analizzati il biovetro, il biosmalto e ndrossiapatite. Il biovetro ed il biosmalto appaiono al momento materiali interessanti, ma non ancora tali da trovare in chinirgia ortopedica un preciso campo di applicazione. L'idrossiapatite è il ceramico bioattivo che trova attualmente le maggiori possibilità di impiego clinico. L'intimo legame di interfaccia che stabilisce col tessuto osseo ne permette infatti l'utilizzazione come riempitivo di difetti ossei in varie patologie scheletriche e come rivestimento di substrati protesici metallici.Ceramic materials utilized in orthopaedic surgery can be divided into bioinert, causing minimum tissue reaction, and bioactive types, capable of stimulating bone tissue growth, establishing a bond capable of supporting physiological loads. Alumina is a bioinert ceramic which shows excellent mechanical resistance and an extremely low level of wear when given appropriate structural characteristics. It is therefore used to make prosthetic hip components (head and acetabulum), to coat metal prosthetic shafts and to make prostheses for small joints. Among the bioactive ceramics, bioglass, bioglaze and hydroxylapatite are included in the study. At present, bioglass and bioglaze appear interesting, but not sufficiently so as to find a precise niche in orthopaedic surgery. Currently the bioactive ceramic with the most possibilities for use in orthopaedic surgery is hydroxylapatite. The close interfacial bond which is established with bone tissue allows it to be used as a filler for defective bones in various skeletal diseases and as a coating for metal prosthetic substrates.

1992 - In vivo study of a new active glass for bone repair: short term result [Relazione in Atti di Convegno]
Gatti, Antonietta; Zaffe, Davide; O. H., Andersson
abstract

The "in vivo" behaviour of a new active glass, as granules, was checked for 3 months in mandibular sheep's bone. After explantation, SEM observations and X-ray microanalysis on the mandibular sections were carried out. New formed bone grew directly on the granules that show a biodegradation.

1992 - Interfacial study of some inert and active ceramics implanted in bone [Relazione in Atti di Convegno]
Zaffe, Davide; S., Giannini; A., Moroni; A., Krajewski; A., Ravaglioli
abstract

Cylinders of biologically inert (Alumina and Zirconia) and active (Hydroxyapatite, Bioglass and AKRA 15 glass) ceramics, were inserted as a press-fit for 6 and 12 months in the femurs of adult Merinos sheep. It resulted that all the cylinders were surrounded by an envelope of new cortical bone; however those made up of inert ceramic were separated from the bone by a capsule of loose connective tissue, whereas a direct contact occurred between the new formed bone and the active ceramics cylinders, except for AKRA 15 rods whose surfaces appeared to be almost compietely covered by fibrous tissue. A bidirectional flow of ions occurred in the outer reactive layer of the two glasses examined. The results are discussed in relation with the biological behaviour of the tested materials in bone implants.

1992 - Jawbone enlargement using immediate implant placement associated with a split-crest technique and guided tissue regeneration. [Articolo su rivista]
M., Simion; M., Baldoni; Zaffe, Davide
abstract

Five patients with sufficient vertical bone height but insufficient bone width for implant placement were chosen for treatment with a split-crest technique combined with guided tissue regeneration. The surgical technique involved splitting the alveolar ridge longitudinally in two parts, provoking a greenstick fracture. A chisel was then used to make a fine cut and spread apart the two cortical plates. Implants were then placed. Implants and defects were covered with expanded polytetrafluoroethylene membranes. Biometrical examination showed a gain in bone width, varying between 1 and 4 mm; maxillary sites showed greater ridge enlargement. Histologic examination showed regeneration of bone tissue between the two portions of the split crest. This membrane technique could be effective and predictable for horizontal ridge augmentation associated with immediate implant placement.

1991 - Analysis of the interface between bone and an active surface glass [Capitolo/Saggio]
Gatti, Antonietta; Zaffe, Davide; T., Yamamuro
abstract

Aim of the work is the evaluation of the interface developed by an active surface glass with sheep mandibular bone. Granules of 60-mesh size of a SIO2-CaO-Na20-MgO glass were implanted in bone defects surgically created in two sheep' jaws. After 2 and 4 months from the implant, the jaw sections were analyzed under SEM and X-ray microprobe. The analyses showed new bone formation along the wall of the cavity, and also at the center of the hole. The bone trabeculae try to surround the granules and develop a direct contact with the glass. The ion diffusion develops a Ca-P rich layer at the border of the granules and an incorporation of Silicon in bone and connective tissue adjacent to the glass.

1991 - Histological and physico-chemical analyses on transformations of some bioactive glasses implanted in long bones of rabbit and sheep [Capitolo/Saggio]
Zaffe, Davide; A., Moroni; V., Pezzuto; S., Contoli; A., Krajewski; A., Ravaglioli
abstract

Rods of a Hench-type and AKRA 15 glasses, and steel cylinders and plaques coated with AKRA 15 were implanted for various periods of time in long bones of rabbit and sheep. The sections of undecalcified, methacrylate embedded segments of bone containing the prostheses, were analyzed under optical microscope, scanning electron microscope, X-rays microprobe and on microradiographs. It resulted that there is: a) a direct contact of bone with the most part of Hench rods; b) an envelope made up of cortical bone surrounding the external part of AKRA rods and completely the coated-steel prostheses; c) a centrifugal diffusion of the main elements of the glasses in the degraded layer, towards the biological environment; d) a centripetal diffusion in the degraded layer, from the surrounding tissues, of Calcium and Phosphorus in the Hench-type glass and, in the AKRA 15 glass, also of Potassium. These results are discussed in relation to the ions that should be taken into account in preparing bioactive glasses.

1991 - Long-Term Behavior Of Active Glasses In Sheep Mandibular Bone [Articolo su rivista]
A. M., Gatti; Zaffe, Davide
abstract

Granules of a glass (A) prepared according to Hench's formula and a new vitreous material for biological applications (AKRA 15) were used for repair of bone defects in the dental field. The behaviour of these materials implanted in holes drilled in sheep's mandibular bone was examined 4, 8, 12 month after implantation. Microradiographic analyses, optical and scanning electron microscopic observations, and X-ray microprobe evaluations were carried out using undecalcified, methacrylate-embedded sections of the jaw containing the granules. After one year the granules of A disappeared, but not important bone growth was observed also in the holes containing AKRA 15. SEM and microprobe showed: disappearance of Na and Si ions at different stages; increase of P and Ca up to 4 month and then decrease, but in different ways in the two glasses; unexpected appearance of K ions after 4 month only in AKRA 15.

1991 - Rigenerazione guidata dei tessuti in osteointegrazione II - Siti post-estrattivi [Articolo su rivista]
M., Simion; M., Baldoni; Zaffe, Davide
abstract

La possibilità di inserire impianti in siti post-estrattivi immediatamente dopo l'avulsione dell'elemento dentario comporta il vantaggio di ridurre il tempo di trattamento e di eliminare il riassorbimento di osso alveolare che avviene dopo ogni avulsione. Le tecniche di rigenerazione guidata dei tessuti sono state proposte da vari Autori al fine di impedire la colonizzazione da parte dei tessuti connettivo ed epiteliale dello spazio tra impianto e pareti dell'alveolo residuo. In questo lavoro vengono descritte due tecniche chirurgiche che prevedono la prima una esposizione precoce della membrana al cavo orale, la seconda una completa copertura della membrana per tutto il periodo di guarigione. I dati ottenuti con le due tecniche sono comparati sotto il profilo biometrico e le membrane esposte vengono esaminate al SEM ed al TEM dal punto di vista microbiologico ultrastrutturale. La tecnica che prevede la completa copertura della membrana per tutto il periodo di permanenza in situ ha fornito i risultati più soddisfacenti.The possibility to introduce implants in fresh extraction sockets offers the advantage of shortening the treatment period and limiting alveolar bone resorption after extraction. Several authors suggested guided tissue regeneration to prevent connective and epithelial tissue proliferation between implant and the residual alveolar space. The present work describes two different surgical techniques. In the former the membrane is exposed soon after placement in the buccal cavity. The later on the contrary is performed with complete closure of the membrane for the whole healing period. The results obtained with both techniques are compared according to their biometrical aspect and the exposed membranes are observed at SEM and TEM with reference to their microbiological structure. The procedure with complete covering of the membrane for the whole healing period gave the most satisfactory results.

1991 - Short-Term Behavior Of 2 Similar Active Glasses Used As Granules In The Repair Of Bone Defects [Articolo su rivista]
Gatti, Antonietta; Zaffe, Davide
abstract

The bioactivity of two similar vitreous materials used in the form of granules of 'critical' size was investigated in bone defects in jaws of two sheep. The granules consisted of Hench's Bioglass(R) and another glass with the same chemical composition made in Italy. Two months after implantation, the sheep were killed and elemental analyses carried out on sections of the embedded jaws. The microanalyses for both the glasses showed a diffusion from the granules towards the surrounding tissue of silicon and sodium, and an inverse diffusion (from the surrounding tissue towards the granules) of calcium and phosphorus. The degradation for the Italian glass was slower than for the Bioglass. No significant osteoinduction was seen after that time at the interface of the glass granules or in the bone pocket.

1991 - Success and failure of experimental active glasses in periodontal disease repair [Capitolo/Saggio]
Zaffe, Davide; Gatti, Antonietta
abstract

Four different ceramic materials, both inert and active, used in granule form for bone repair, were implanted in two sheep's jaws. After 3 months from the implant, the behaviour of the materials was studied by means of SEM and X-ray microprobe on thick sections of the embedded undecalcified jaws. The unexpected success of the inert materials and the failure of the used bioactive glass opens the problem of the calibration of the degradation parameters that must be evaluated both on the massive material and also on the granules or powders.

1990 - Aspetto biotecnologico di impianti dentari con 3 biovetri a drogatura diversa nella pecora [Articolo su rivista]
Zaffe, Davide; Gatti, Antonietta; G. P., Poli; A., Krajewski; A., Ravaglioli
abstract

Polveri di 3 tipi di vetri a superficie attiva, diversi per agenti droganti controllanti la velocità di degradazione, sono stati posizionati nell'osso mandibolare di 3 pecore adulte, sacrificate rispettivamente a 4, 8 e 12 mesi dall'impianto. Le valutazioni condotte sulle sezioni dei pezzi inclusi hanno comportato: osservazioni microradiografiche, al microscopio ottico, al microscopio elettronico a scansione ed analisi alla microsonda EDS. I risultati hanno messo in evidenza le diverse velocità di degradazione dei tre biovetri, i relativi cambiamenti strutturali e le rispettive variazioni morfologiche. Gli stimoli osteogenetici risultano comunque estremamente limitati o nulli in tutti i vetri.Powders of three surface-active glasses were implanted in the jaws of three sheep which were sacrificed respectively 4, 8 and 12 months. The osteogenetic and biodegrading activity was studied in three glasses differing only in the content of the doping agents that check the biodegradation velocity. The evaluations, carried out on the sections of the embedded samples, implied microradiographic analyses and observations under optical and scanning electron microscope with microprobe for elemental analyses. The results showed different degradation velocities of the glasses and their morphological and structural changes. All the glasses showed a very limited osteogenetic stimulation.

1990 - Behavior Of Tricalcium Phosphate And Hydroxyapatite Granules In Sheep Bone Defects [Articolo su rivista]
Gatti, Antonietta; Zaffe, Davide; G. P., Poli
abstract

Granules of hydroxyapatite (HA) and tricalcium phosphate (TCP) were implanted in separate holes drilled in mandibular bone of sheep to check the bone growth and in vivo behaviour of the materials. The experiment was performed in three sheep, killed respectively at 4, 8, 12 month. Samples of bone with the materials were explanted, microradiographed and sectioned to evaluate the interface under optical and electron scanning electron microscope. The hole, left empty as a reference, showed no full repair; whereas 4 month after implantation the TCP granules induce total repair of the hole. HA granules crumbled and no new bone induction was seen even 12 month after implantation.

1990 - Biodegradation of three different bioactive glasses for the repair of bone defects in dentistry [Relazione in Atti di Convegno]
Gatti, Antonietta; Zaffe, Davide; G. P., Poli; A., Ravaglioli; A., Krajewski
abstract

Granules of three different types of new active glasses (A, AKRA 15, AKRA 18) were implanted in holes surgically created in sheep's jaws in order to check their biodegradation at different times (2, 4, 8 and 12 months). The results show that: a) no osteodeposition occurs even after 12 months from the implant; b) after 8 months, only AKRA 15 granules are stili present in the hole, and after 12 months al so these granules disappear completely; e) after 2 months all the elements of the three glasses diffuse toward the biological surroundings with different velocities; d) in the outer degradation zone of the granules, a Ca-P rich layer exists, but the Ca/P ratio is such as to take into consideration a diffusion of these ions from the biological environment toward the glass surface.

1990 - Characterization of a high performance duplex stainless steel for orthopedic applications [Relazione in Atti di Convegno]
A., Cigada; F., Amici Jr; M., Cavallini; G., De Sanctis; Gatti, Antonietta; M., Giacomazzi; G., Rondelli; A., Roos; B., Vicentini; Zaffe, Davide
abstract

In the paper are illustrated the results of an extensive investigation performed by a research working group constituted by nine laboratories, with the target to study a material alternative to the traditional ASTM F138 austenitic stainless steel. In particular a 25Cr-7Ni-4Mo-0.28N austeno-ferritic duplex stainless steel, with high molybdenum and nitrogen contents, was developed. All the in vitro, in vivo on animals, and clinical results obtained tilt now have shown that the proposed steel can be suggested as a convenient substitute for the ASTM F138 steel because it is not susceptible to crevice corrosion in the human body and has better mechanical properties (in particular better fatigue resistance) than the traditional one.

1990 - Comparative analyses among interfaces of some ceramic materials and bone in sheep. [Articolo su rivista]
Zaffe, Davide; Gatti, Antonietta; Poli, G. P.; Ravaglioli, A.; Krajewski, A.
abstract

Aim of this work is the evaluation of "in situ" implants in an animal model to study the interfaces that some ceramic materials for dental bone defects develop with bone and to check which material is more osteoconductive. In a sheep's jaw, eight holes were drilled and filled with six ceramic materials in granular shape. Two bilateral holes were left empty as reference. The ceramic materials were: porous tricalcium phosphate (TCP), porous hydroxylapatite (HA) and four bioactive glasses. The glasses differ for doping agents that affect the velocity of biodegradation in the living body. Monthly radiographs were taken and the X-ray pictures analyzed by means of a Video Display Computer in order to quantify the optical density changes occurred in the holes. After 4 months implantation, the segments of the jaw containing the materials were fixed in paraformaldehyde, embedded in methylmethacrylate and sectioned. The results obtained under the microradiograph, the SEM and the X-ray microprobe showed a good bone repair only with TCP granules. A great degradation was seen in HA granules and particularly in glasses. The degradation modified the structure and the composition of the glass granules, but it was not followed by a consequent bone deposition.

1990 - Comparative Histological and Chemical-Physical Analyses on Alumina, Bioactive Glass, Bioglaze and Hydroxylapatite Sheep Bone Implants [Relazione in Atti di Convegno]
A., Moroni; S., Giannini; Zaffe, Davide; Ravaglioli, A; Kraiewsky, A.; A., Venturini; M., Pompili; S., Cantagalli; V., Pezzuto; L., Trinchese
abstract

Four samples of alumina, bioactive glass, bioglaze and hydroxylapatite were obtained in the shape of a cylinder (height 10 mm, diameter 4 mm) and numbering four for each of the bioceramics. The samples were implanted into predrilled holes in the lateral cortex of four adult merino sheep femurs. Six months after surgery the animals were sacrificed. The results show that all the samples were surrounded by newly deposited bone. Alumina samples were surrounded by bone which never came into direct contact with the surface of the samples.The bioactive glass samples showed a direct contact with bone, the bioglaze samples instead, appeared surrounded by fibrous tissue. In both the glass compositions a thick degradation surface layer was observed. Hydroxylapatite samples were totally surrounded by bone structured in longitudinal osteons that came into direct contact with the surface of the implants.

1990 - Implantations dentaires en alumine monocrystalline chez l'animal: étude du tissu périmplantaire [Monocrystalline aluminum dental implants in animals: a study of the peri-implant tissue] [Articolo su rivista]
Gatti, Antonietta; Zaffe, Davide; G. P., Poli
abstract

After the extraction of two molars in a dog's jaw, a single crystal alumina screw was implanted. Monthly radiographs were taken and analyzed by means of a video display computer (VDC) to obtain densitometric informations about the interface. After one year implantation, the bone segment containing the prosthesis was fixed in 4\% paraformaldehyde, embedded in methacrylate and sectioned by a microtome saw. The results in light microscopy with ordinary and polarized light, in SEM and X-ray microanalysis, show the presence of a thick connective tissue layer interposed between the screw and the bone. The histological findings confirm the results obtained through the VDC analysis of the radiographic images.

1990 - In vitro and in vivo behaviour of a NiTi shape memory alloy [Relazione in Atti di Convegno]
A., Cigada; G., De Sanctis; Gatti, Antonietta; G., Rondelli; B., Vicentini; Zaffe, Davide
abstract

The in vitro corrosion properties and the in vivo interaction with biological environment of a NiTi shape memory alloy were evaluated and compared to a TI6Al4V alloy. The passivity currents were evaluated in vitro by an electrochemical method. The in vivo tests were performed by implantation of cylindrical specimens and special crevice devices on rabbits' femur. Some problems related to the in vitro and in vivo behaviour of the NiTi alloy are pointed out.

1990 - Osteocyte Differentiation In The Tibia Of Newborn Rabbit - An Ultrastructural-Study Of The Formation Of Cytoplasmic Processes [Articolo su rivista]
Palumbo, Carla; Palazzini, Silvana; Marotti, Gastone; Zaffe, Davide
abstract

The morphological changes undergone by the osteoblast at the ultrastructural level, during its differentiation into osteocyte, were studied in the primary parallel-fibred bone of the newborn rabbit by means of incomplete three-dimensional reconstruction from partially serial-sectioned preosteocytes. The findings obtained suggest that the formation of osteocyte cytoplasmic processes is an asynchronous and asymmetrical phenomenon that seems to precede the mineralization of the organic matrix and to give rise to an asymmetrical mature osteocyte. The functions of cytoplasmic processes as regards bone formation, cell nutrition and osteoblast modulation are discussed. The mechanism by which the osteoblast 'enters' the bone matrix is hypothesized.

1990 - Osteogenesi imperfetta. Primi dati sulle alterazioni strutturali riscontrate nei tessuti mineralizzati di un dente [Articolo su rivista]
Zaffe, Davide; Marotti, Francesca; A., Cheli
abstract

Struttura e grado di mineralizzazione sono stati analizzati nello smalto e nella dentina del 2° dente premolare permanente dell'emimandibola sinistra in una paziente affetta da osteogenesi imperfetta tipo III (sindrome di Ekman-Lobstein). Dopo una breve descrizione del caso clinico, con particolare riferimento alle patologie dentaria e scheletrica, vengono riportati i risultati preliminari dello studio istopatologico. Essi dimostrano la presenza di difetti di mineralizzazione sia nello smalto che nella dentina. Nello smalto, le zone ipocalcificate si trovano solamente lungo la giunzione con la dentina, come in genere si riscontra nei denti normali; esse risultano, tuttavia, più estese di quelle fisiologiche. Non sono, pertanto, da ritenersi difetti primari dell'amelogenesi ma secondari alla dentinogenesi imperfetta. Al contrario, nella dentina, le zone ipocalcificate appaiono disseminate nelle regioni sia mantellare che circumpulpare. Rispetto alla dentina normocalcificata, queste zone osservate a luce polarizzata presentano le fibre collagene irregolarmente intrecciate. I risultati ottenuti sono brevemente discussi in relazione sia ai processi di deposizione dello smalto e della dentina sia alla resistenza fisica dei denti di pazienti affetti da osteogenesi imperfetta tipo III.By means of the light microscope, under ordinary and polarized light, and the microradiography the structure and degree of mineralization of enamel and dentin were studied in the permanent 2nd premolar tooth of the left emimandible in a patient afìfected by type III osteogenesis imperfecta (Ekman-Lobstein syndrome). After a brief description of the clinical case, with particular reference to skeletal and dental pathologies, the preliminary results of the histopathological analysis are reported. They show the existence of defects of mineralization in both enamel and dentin. In the former, the hypocalcified areas are only located close to the enamel-dentin junction, as it usually occurs in normal teeth; however, they look broader than physiological ones. Thus they do not seem to be primary defects of amelogenesis but secondary ones, due to dentinogenesis imperfecta. On the contrary, in dentin, the hypocalcified areas are scattered throughout both mantle and circumpulpal regions. In the hypocalcified areas, compared with normally mineralized dentin, collagen fibers appear to be irregularly interwoven under polarized light. The results obtained are briefly discussed in relation to the processes of enamel and dentin deposition, and to the physical resistance of the teeth in type III osteogenesis imperfecta.

1989 - Experimental dental implant in dog: evaluation of the interface with bone [Relazione in Atti di Convegno]
Gatti, Antonietta; G. P., Poli; Zaffe, Davide
abstract

No abstract

1989 - Indagine istologica sull'interfaccia osso-biovetro [Articolo su rivista]
Gatti, Antonietta; Zaffe, Davide; G. P., Poli; A., Ravaglioli; A., Krajewski
abstract

I biovetri, nuovi materiali per riempimenti delle tasche parodontali attualmente allo studio, rilasciano nei tessuti ioni essenziali per l'osteogenesi. La sperimentazione in vivo consente di valutarne il comportamento nel tempo

1989 - La madrepora come riempitivo osseo [Madrepore as a bone filler] [Articolo su rivista]
M., Tassinari; E., Cantoni; P., Guazzi; Zaffe, Davide
abstract

È stato studiato il comportamento del corallo, di tipo ponte, impiantato nell'uomo in qualità di riparatore di difetti ossei parodontali. L'analisi istomorfologica al microscopio ottico, SEM e microsonda a raggi X sul materiale non decalcificato di una carota bioptica, prelevata con un apposito utensile, ha evidenziato che attorno ai grani di corallo si è neodeposto dell'osso. Questo tessuto, dopo 6 mesi di impianto, si presentava stabile e privo di attività osteoclastica, assente anche nei confronti di tutti i grani impiantati.Pur in accordo con quanto affermato da Souyris e Coll., gli Autori non concordano sulla sostituzione totale, almeno a breve termine, del corallo con osso, dato questo che dovrà essere successivamente verificato con ulteriori ricerche.The Authors studied the behaviour of the porite type coral which has been previously implanted in man in order to get a reparation of osseous and parodontal defects. The histomorfological exam (at the optical microscope, SEM and X-Ray microscope) of a non decalcified bioptic piece, which had been obtained with an appropriate instrument, shows a deposition of neoformed bone around the coral. Six months after the implantation the tissue was stable without any osteoclasts activity; even the implanted coral grains had not been attached by them.The Authors agree with most of the statements made by Souyris et Al, but they do not believe in the total substitution of the coral with the bone, at least not in short terms: therefore further scientific works will be necessary to clear this point.

1989 - Studio istochimico e ultrastrutturale della calcificazione in protesi valvolari cardiache di pericardio bovino [Articolo su rivista]
Muglia, Maria Antonietta; Zaffe, Davide; Marotti, Gastone; Gatti, Antonietta; G., Noera
abstract

É stato condotto uno studio istochimico ed ultrastrutturale su lembi valvolari cardiaci costruiti con pericardio bovino pretrattato con glutaraldeide e impiantati per 3 e 20 giorni nell'ostio della tricupside di pecora. È risultato che, già in un periodo sperimentale così breve, si attua una evidente calcificazione distrofica che inizia dalle cellule per estendersi successivamente alla sostanza fondamentale e alle fibre collagene. Il problema della fissazione, praticata prima del modellamento dei lembi valvolari protesici, viene discusso ai fini di prevenire o, quanto meno, dilazionare nel tempo la loro calcificazione.A histochemical and ultrastructural study was carried out on bioprosthetic heart valves fabricated from glutaraldehyde-treated bovine pericardium. It resulted that a periodi the mineralization first occurs in cell protoplasma and then in the ground substance and collagen fibers. The problem of fixation, made before modeling the semilunar bioprosthetic cusps, is discussed as regards the attempt to prevent or to delay their calcification.

1987 - Early stages of osteocyte differentiation: a three-dimensional ultrastructural study. [Abstract in Rivista]
Palumbo, Carla; Zaffe, Davide; Palazzini, S.; Marotti, Gastone
abstract

The osteocyte processes emrging fron the mineral-facing side are mainly involved in matrix formation and mineralization, while those of the vascular-facing side have a trophical function and probably also modulate the activity of the adjacent osteoblasts.

1987 - Indagine morfofunzionale sul processo di differenziamento dell'osteoblasta in osteocita [Articolo su rivista]
Palumbo, Carla; Zaffe, Davide; Palazzini, Silvana; Marotti, Gastone
abstract

No riassunto

1987 - The evaluation of the interface between bone and a bioceramic dental implant. [Articolo su rivista]
Gatti, Antonietta; Zaffe, Davide; G. P., Poli; Galetti, Riccardo
abstract

Methods for evaluating the interface between bone and an experimental dental implant have been analyzed. The material studied was a titanium implant coated with a mixture of alumina and titanium dioxide by means of a plasma-jet system with the dog as the animal model. The evaluations were made on two levels: (1) in vivo, by analyzing radiographs of the peri-implant zone with a video display computer (2) in vitro, after explantation, by analyzing vertical and horizontal sections of the sample with an optical and a scanning electron microscope, and by a video display computer analysis of the microradiographs of these sections.

1987 - Utrastruttura della placca di accrescimento fibrosa nella metafisi prossimale della tibia di coniglio [Articolo su rivista]
Marotti, Gastone; Palazzini, Silvana; Zaffe, Davide
abstract

No riassunto

1987 - Valutazione comparativa multipla dell'interfacie osso-impianti dentari [Articolo su rivista]
Gatti, Antonietta; Zaffe, Davide; Galetti, Riccardo; G. P., Poli
abstract

Sono stati impiantati su mandibole di cane, 3 diversi impianti metallici, tutti rivestiti di un materiale ceramico. Le protesi sono state lasciate "in situ" per il periodo di un anno. Durante questo arco di tempo veniva controllata l'interfacie osso-impianto mediante analisi delle lastre radiografìche delle zone per mezzo di un analizzatore digitale di immagini. La protesi e l'osso circostante, dopo l'espianto, sono state incluse in metilmetacrilato e quindi il campione sezionato con microtomo a lama circolare. Lo studio morfologico delle sezioni è stato condotto con il microradiografo, microscopio ottico in luce trasmessa ed in luce fluorescente, elettronico a scansione e con la microsonda elettronica. La comparazione dei risultati evidenzia la buona biocompatibilità ed il maggior aggancio meccanico instaurato dall'impianto di titanio.Three metallic prostheses coated with ceramic material were implanted in dog's jaws. Prostheses remained "in situ" for a year. During that time the bone-implant interface was checked with analysis of radiographic pictures of the zone by means of a digital analyzer of images. After the explant, the prosthesis and the surrounding bone, embedded in methylmethacrylate, were sectioned in order to evaluate the morphology of the interface. Analyses were carried out by microradiograph, optical and scanning electron microscope, microprobe. Comparing the results shows the good biocompatibility and the very good mechanical bond of the titanium implant.

1986 - L'osteogenesi nelle protesi d'anca avvitate SCL [Articolo su rivista]
F., Marotti; A., Moretti; Muglia, Maria Antonietta; M., Pozzi Mucelli; Zaffe, Davide
abstract

No riassunto

1985 - A SEM study of osteocyte orientation in alternately structured osteons. [Articolo su rivista]
Marotti, Gastone; Muglia, Maria Antonietta; Zaffe, Davide
abstract

Previous morphometric analyses, carried out by means of the light microscope show the existence of a close relationship between size, shape, orientation of osteocytc lacunae and collagen texture in both woven bone and longitudinally structured secondary osteons (Marotti 1979, 1980). However these investigations, owing to the technique applied, failed to demonstrate the orientation of the triaxial osteocyte ellipsoids in lamellar bone with alternate orientation of fibers. In the present study the SEM was used to measure the sectional area and the axes of osteocyte lacunae in secondary osteons with different types of lamellation. Compact bone from tibiae of normal men of various age was etched with N/10 HCl for 90", and treated with Trypsin (80 µg/ml, pH 7.4 for 41h at 37°C) before being gold-palladium coated for the SEM analysis. The results obtained are in close agreement with those of the previous investigations as regards the orientation of osteocytes in woven bone and in longitudinally structured osteons. Tn addition they show that in lamellar osteons with alternate orientation of fibers the osteocytes are mainly located in longitudinally structured lamellae with their major axis at an angle of 26-27° with respect to the longitudinal axis of the Haversian canal.

1985 - Quantitative investigation on osteocyte canaliculi in human compact and spongy bone. [Articolo su rivista]
Marotti, Gastone; Remaggi, Francesca; Zaffe, Davide
abstract

By means of the two techniques (reflected polarized light and SEM) used in previous investigations (Remaggi et al., Calcif. Tissue Int., suppl. 3b, 26, 1983), the number of canaliculi departing from osteocyte lacunae was counted in compact and spongy bone of human tibiae from normal subjects of different ages.The statistical analysis of the results indicates that in both compacta and spongiosa the extension of the canalicular network is significantly greater in woven than in lamellar bone. In the latter, moreover, the number of canaliculi per unit lacunar surface appears to be proportional to the size of the lacunae and greater in lacunar walls facing the vascular source than in the opposite walls facing the cement line. This occurs in secondary osteons and in fragments of spongy trabeculae outlined by reversal lines.These results strongly suggest the hypothesis that the metabolic activity of the osteocytes differs according to the type of bone tissue and in different skeletal regions.

1985 - Relationship between estrogen receptor concentration and cytomorphometry in breast cancer. [Articolo su rivista]
A., Guazzi; C., Bozzetti; M. I., Riva; Zaffe, Davide; G., Cocconi
abstract

This study aimed to evaluate the relationship between estrogen receptor (ER) concentration and cytomorphometric parameters in breast carcinoma. Primary breast cancer specimens were both imprinted on cytologic slides and submitted to ER determination with a dextran-coated charcoal method. Patients were stratified by ER levels ranging from 0 to greater than or equal to 200 fmol/mg protein. Measurements were performed on cytologic imprint technique smears in five cases from each ER strata, using a computer-assisted tracing device. Nuclear, cytoplasmic, and cellular parameters were measured on 50 cells per case. The cytometric findings were correlated with ER concentrations. A statistically significant correlation between decreasing area (P = 0.011), perimeter (P = 0.015), maximum diameter (P = 0.034), minimum diameter (P = 0.008), and volume (P = 0.01) of nuclei and increasing ER levels was found. With regard to whole cells, the following parameters significantly decreased versus increasing ER levels: area (P = 0.038), perimeter (P = 0.046), minimum diameter (P = 0.011), and volume (P = 0.044). A statistically significant relationship between the decreasing cytoplasmic perimeter (P = 0.025), i.e., nuclear plus cellular perimeter, and increasing ER content was found. Cytoplasmic area and nuclear to cytoplasmic ratio (N/C) did not correlate with the amount of ER. In all classes of different ER concentration, cells and nuclei displayed a regular shape closer to a circle than to an ellipse. The results of the current investigation indicate that tumors with higher ER concentration are composed of smaller cells with smaller nuclei than are tumors with lower ER content.

1985 - Studio di un impianto dentario di acciaio rivestito di allumina [Articolo su rivista]
Gatti, Antonietta; Zaffe, Davide; Galetti, Riccardo; G. P., Poli
abstract

No riassunto

1984 - Modificazioni della struttura dell'osso osteonico nella fluorosi industriale [Changes in the structure of osteonic bone in industrial fluorosis] [Articolo su rivista]
Palazzini, Silvana; Remaggi, Francesca; Zaffe, Davide; Muglia, Maria Antonietta; Canè, Valerio; Marotti, Gastone
abstract

E stata condotta un'indagine comparativa al microscopio ottico a luce ordinaria e a luce polarizzata su sezioni centrodiafisarie di ossa metacarpali di bovini affetti da fluorosi industriale.I reperti istologici osservati concordano con quelli riportati in letteratura per quanto concerne sia la disorganizzazione del collagene sia la presenza di lacune osteocitarie anomale negli osteoni secondari. I risultati delle nostre osservazioni, in accordo con i dati morfometrici, indicano però che entrambi i tipi di lacune patologiche già descritti in letteratura, le cosiddette «mottled» ed «enlarged» lacune, sono per forma, densità e dimensioni del tutto identiche alle lacune che si trovano nell'osso a fibre intrecciate normale e che inoltre sono sempre localizzate in porzioni di osteoni secondari dove il collagene non è organizzato come di norma a lamelle ma a fibre intrecciate.Se ne deduce, contrariamente a quanto sostenuto da altri autori, che ambedue i tipi di lacune patologiche sono da considerarsi il risultato di una stessa noxa, ossia di una interferenza del fluoro sul metabolismo degli osteoblasti, con conseguente anomala deposizione di osso a fibre intrecciate negli osteoni secondari.A comparative investigation under ordinary and polarized light was carried out on metacar-pal bones from normal and fluorotic bovines. The histologic findings agree with those reported in literature as regards the disorganisation of collagen and the presence of abnormal osteocyte lacunae in the secondary osteons (Fig 1). Three types of pathologic haversian systems were observed: osteons with large lacunae near the cement line, osteons with «mottled lacunae», and osteons with lacunae showing an intermediate aspect (Fig. 2). Microradiographic analysis showed patches of lower degree of radiopacity in «mottled» areas, but the former appears of lower extension than the latter (Fig. 2b). The results of our observations, in agreement with the morphometric data (Fig 6), show that both types of pathologic lacunae described in literature (i.e. the so-called «mottled» and «enlarged» lacunae) are identical in shape, size and density with the lacunae found in normal woven bone (Fig 7); moreover, that these lacunae are always located in portions of secondary osteons where the collagen is not organized in lamellae, as normally, but in woven fibres (Fig 3, 4).As against what has been maintained by other authors, we conclude that both types of abnormal lacunae must considered the result of an identical pathological phenomenon: that is to say, an interference by fluoride in the metabolism of the osteoblasts, with a consequently abnormal deposit of woven bone in the secondary osteons.

1983 - Aspetti ultrastrutturali della cartilagine articolare di bovino in condizioni di deformazione totale e residua [Ultrastructural aspects of bovine articular cartilage under conditions of total and residual deformation] [Articolo su rivista]
A., Bottazzi Bacchi; Muglia, Maria Antonietta; Zaffe, Davide
abstract

Provini di forma cubica (1 cm di spigolo) costituiti da cartilagine articolare e da uno straterello di osso spugnoso, isolati dall'epifisi prossimale del metacarpo di bovini di 2-3 anni, vennero sollecitati con carichi superiori a quelli fisiologici, compresi tra 20 e 180 Kg/cm2. I provini vennero fissati in glutaraldeide tamponata mentre la pressione era in atto (saggio della deformabilità totale) oppure 15' minuti dopo lo scarico (saggio della deformabilità residua). Dopo postfissazione in tetrossido di osmio ed inclusione in araldite, la parte cartilaginea dei provini venne sezionata con l'ultramicrotomo in corrispondenza dell'area compressa.L'osservazione ultrastrutturale dei frammenti non sollecitati di controllo, conferma quanto già si sapeva dalla letteratura e, cioè, che i condrociti della cartilagine articolare degli individui in accrescimento sono elementi metabolicamente attivi: il loro citoplasma contiene un reticolo endoplasmico rugoso ed un apparato di Golgi assai sviluppati, scarsi mitocondri, numerosi filamenti talora disposti in fasci, gocce lipidiche e granuli di glicogeno.In condizioni di deformazione totale, i corpi cellulari, schiacciati secondo l'asse di sollecitazione, risultano più appiattiti al centro, per il fatto che i materiali paraplasmatici tendono a defluire verso la periferia della cellula; profondamente deformati ed alterati appaiono i vari organuli. Sotto carichi elevati, la membrana plasmatica si può rompere, lasciando fuoriuscire il citosol e gocce lipidiche. In condizioni di deformazione residua, i condrociti non presentano mai segni di recupero, a differenza della sostanza intercellulare che tende a ritornare più lassa in particolare sotto i carichi minori usati (20 Kg/cm2); si forma pertanto uno spazio tra la membrana plasmatica e la parete della nicchia. Il danno ultrastrutturale risulta ovviamente tanto maggiore quanto più elevato è il carico pressorio.ULTRASTRUCTURAL ASPECTS OF BOVINE ARTICOLAR CARTILAGE UNDER TOTAL AND RESIDUAL DEFOR-MATIONCubic samples (1 cm side) of articular cartilage and of the underlying spongiosa isolated from the proximal epiphysis of the metacarpal bone of cattle aged 2-3 years were subjected to compressive stress lighter than the physiological ones (from 20 to 180 Kg/cm2).The samples were fixed in buffered glutaraldehyde while under pressure (test of total deformation) or 15' minutes after unloading (test of residuai deformation). The cartilaginous layer of the samples was postfixed in osmium tetroxide, embedded in Araldite and sectioned with the Ultratome in the compressed area.The ultrastructural observations of the unloaded specimens, taken as controls, are in dose agreement with the data reported in literature. They show that chondrocytes in the articular cartilage of growing bovines are metabolically active cells. Their cytoplasm contains a prominent Golgi apparatus and a variable concentration of granular endoplasmic reticulum, few mitochondria, lipid droplets, glycogen granueles and several filaments often closely packed (Figs. 1, 2, 3).Under total deformation (Figs. 4, 5, 7), the chondrocytes appear to be squeezed according to the pressure axis, and more flattened in the centre because of the diffluence of the paraplasmatic materials towards the external boundary of the celi; the various organelles are strongly deformed and altered. Under the highest loads, the cytoplasmic membrane can get broken leaving cytosol and lipid droplets going out.Under residuai deformation (Figs. 6, 8), chondrocytes never show signes of resilience, while the intercellular substance shows a certain degree of restoration particularly under the lowest load used (20 Kg/cm2); consequently, a space appears between the cytoplasmic membrane and the lacunar wall. Obviously, the greater the compressive load, the higher the ultrastructural damage.

1982 - Activity of osteoclasts and osteocytes in compact human bone at various ages, both with and without osteoporosis. [Articolo su rivista]
Muglia, Maria Antonietta; Volpi, Giorgia; Remaggi, Francesca; Canè, Valerio; Palazzini, Silvana; Zaffe, Davide; Marotti, Gastone
abstract

As part of a programme of research designed to assess the respective roles of osteoclasts and osteocytes in the processes of bone resorption, the metabolic activity of these cells was evaluated indirectly by a morphometric method in the compact bone of human tibias from subjects of various ages, both normal and those affected by osteoporosis. Statistical analysis of the quantitative data was in agreement with the microradiographic examination of the sections, and showed that whereas the intensity of osteoclastic resorption varied in the various subjects according to age, periosteocytic osteolysis--in the classical sense of a phenomenon involving widening of the lacunae detectable with the optical microscope--did not occur in compact bone whether it was normal or highly porotic.

1982 - Size and density of osteocyte lacunae in different regions of long bones. [Articolo su rivista]
Canè, Valerio; Marotti, Gastone; Volpi, Giorgia; Zaffe, Davide; Palazzini, Silvana; Remaggi, Francesca; Muglia, Maria Antonietta
abstract

Size and density of osteocyte lacunae were evaluated at different levels of long bones to investigate whether or not the proportion of bone tissue occupied by osteocytes changes in skeletal regions, characterized by clear-cut differences in bone turnover rates. Statistical analysis of the results shows that the mean cross-sectional area of osteocyte lacunae (C) is lowest in compact bone of diaphysis and metaphysis, highest in spongy bone of metaphysis and epiphysis. On the contrary, the mean surface of bone tissue surrounding each osteocyte (T = bidimensional osteocyte territory, indirectly calculated from the number of lacunae/mm2 of bone) is largest in compact bone of diaphysis, smallest in metaphyseal spongiosa, and shows intermediate values in the cortex of metaphysis and in epiphyseal spongiosa. The proportion of bone tissue occupied by osteocyte lacunae (% C/T) appears to follow at different levels of long bones, the same pattern recorded for the data of bone turnover rate, by the tetracycline labeling technique: it is lowest in mid-diaphyses, highest in metaphyses, and intermediate in epiphyses. On the basis of these findings, it is suggested that the action exerted by osteocytes on the surrounding calcified matrix, whatever the function of these cells, is not uniform throughout the skeleton and is to some extent correlated with the activity of the other bone cells-osteoblasts and osteoclasts.The signifìcance of some of the data reported is also discussed in relation to investigations of periosteocytic lacunar morphometry.

1977 - Sull'impiego del Bismarck Brown quale reagente “tipo-Schiff” [Articolo su rivista]
Zaffe, Davide; DE POL, Anto
abstract

Le divergenze tra i diversi ricercatori hanno stimolato l'approfondimento dello studio sul comportamento del Bismarck Brown quale sostituente della Pararosanilina nel reattivo di Schiff. I risultati ottenuti utilizzando il reattivo nelle reazioni Feulgen e PAS, portano alla conclusione che non è possibile considerare questo colorante come un vero "tipo-Schiff".

1972 - Sul test di esclusione del colore. - I Valutazione della concentrazione ottimale [On the dye exclusion of test cell vitality. I. Evaluation of the optimal concentration] [Articolo su rivista]
Forabosco, Antonino; Zaffe, Davide; L., Tosato
abstract

No riassunto

1972 - Sul test di esclusione del colore. - II Influenza di sostanze macromolecolari neutre. [On the dye exclusion test of cell vitality. II. Influence of neutral macromolecular substances.] [Articolo su rivista]
Forabosco, Antonino; Zaffe, Davide; L., Tosato
abstract

No riassunto