Leonardo Trombelli

Clinical outcomes with bioactive agents alone or in combination with grafting or guided tissue regeneration

AIM The purpose of the present review was to determine the clinical effect of the use of bioactive agents (BAs) for the treatment of intra-osseous and furcation defects. MATERIAL AND METHODS The effectiveness of the BAs was evaluated when used in addition to open flap debridement either alone or in association with grafts and/or guided tissue regeneration (GTR). Among the included agents, recombinant human platelet-derived growth factor-BB (rhPDGF-BB), platelet-rich plasma (PRP), commercially available enamel matrix derivative (cEMD) and peptide P-15 (P-15) have been clinically tested for treating periodontal defects. RESULTS AND CONCLUSIONS The results of the present review indicate that: (1) cEMD either alone or in combination with grafts can be effectively used to treat intra-osseous defects and the clinical results appear to be stable long term; (2) the additional use of a graft seems to enhance the clinical outcome of cEMD; (3) the combined use of rhPDGF-BB and P-15 with a graft biomaterial has shown beneficial effects in intra-osseous defects; (4) contrasting results were reported for PRP and graft combinations; and (5) limited evidence supports the use of BAs either alone or in association with graft/GTR for the treatment of furcation defects.

Modeling and remodeling of human extraction sockets.

INTRODUCTION The available studies on extraction wound repair in humans are affected by significant limitations and have failed to evaluate tissue alterations occurring in all compartments of the hard tissue defect. AIM To monitor during a 6-month period the healing of human extraction sockets and include a semi-quantitative analysis of tissues and cell populations involved in various stages of the processes of modeling/remodeling. MATERIAL AND METHODS Twenty-seven biopsies, representative of the early (2-4 weeks, n=10), intermediate (6-8 weeks, n=6), and late phase (12-24 weeks, n=11) of healing, were collected and analysed. RESULTS Granulation tissue that was present in comparatively large amounts in the early healing phase of socket healing, was in the interval between the early and intermediate observation phase replaced with provisional matrix and woven bone. The density of vascular structures and macrophages slowly decreased from 2 to 4 weeks over time. The presence of osteoblasts peaked at 6-8 weeks and remained almost stable thereafter; a small number of osteoclasts were present in a few specimens at each observation interval. CONCLUSIONS The present findings demonstrated that great variability exists in man with respect to hard tissue formation within extraction sockets. Thus, whereas a provisional connective tissue consistently forms within the first weeks of healing, the interval during which mineralized bone is laid down is much less predictable.

Comparative analysis of tetracycline-containing dental gels: Poloxamer- and monoglyceride-based formulations

Abstract The aim of the paper was to develop tetracycline-containing formulations for the treatment of periodontitis by direct periodontal intrapocket administration. Two different semi-solid formulations were prepared, based on poly(oxyethylene)poly(oxypropylene) block copolymer (poloxamer) and monoglycerides, respectively. Both formulations possess interesting properties as delivery systems. They are easily administered by syringe equipped with needles appropriate for intrapocket delivery, they are characterized by a sol-gel transition, becoming semi-solid once in the periodontal pocket and, finally, they represent biocompatible formulations eliminated from the body by normal routes. A rheological characterization of both formulations was performed in the presence or in the absence of tetracycline, determining the sol-gel transition temperature ( T c ) by ‘time cure tests’ and the z coefficient by ‘frequency sweep test’. In addition, the in vitro tetracycline release from formulations was determined. Comparative in vivo studies were conducted, in order (a) to compare the persistence of the gels on the gum and (b) to evaluate the clinical performances of the gels. These latest studies indicated that both poloxamer and monoglycerides gels, when applied subgingivally, produce a significantly improved outcome in moderate to deep periodontal pockets.

Single flap approach with and without guided tissue regeneration and a hydroxyapatite biomaterial in the management of intraosseous periodontal defects

BACKGROUND The single flap approach (SFA) is a minimally invasive procedure designed for periodontal reconstructive procedures of intraosseous periodontal defects characterized by a dominant unilateral, buccal or oral, extension. This study evaluates the adjunctive effect of guided tissue regeneration (GTR) combined with a hydroxyapatite (HA) biomaterial in the management of intraosseous periodontal defects accessed with SFA compared to SFA alone. METHODS Twenty-four intraosseous defects (in 24 patients) were randomly allocated to treatment with SFA or SFA + HA/GTR. Clinical outcomes were assessed 6 months post-surgery. RESULTS Five sites in the SFA + HA/GTR group showed incomplete closure at week 2, which resolved spontaneously. There were no statistically significant or clinically meaningful differences in mean (+/-SD) clinical attachment gain (4.7 +/- 2.5 versus 4.4 +/- 1.5 mm), probing depth reduction (5.3 +/- 2.4 versus 5.3 +/- 1.5 mm), and gingival recession increase (0.4 +/- 1.4 versus 0.8 +/- 0.8 mm) between the SFA + HA/GTR and SFA groups. CONCLUSIONS SFA with and without HA/GTR seems to be a valuable minimally invasive approach in the treatment of deep intraosseous periodontal defects. Under the present experimental conditions, the additional HA/GTR protocol offers no significant adjunctive effect.

Validation of reported genetic risk factors for periodontitis in a large-scale replication study.

AIM Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). MATERIAL AND METHODS We analysed 23 genes in 600 German AgP patients and 1441 controls on the Illumina custom genotyping array Immunochip. We tested a suggestive association in a Dutch and German/Austrian AgP case-control sample, and a German chronic periodontitis (CP) case-control sample using Sequenom iPlex assays. We additionally tested the common known risk variant rs1333048 of the gene ANRIL for its association in a Turkish and Italian population. RESULTS None of the analysed genes gave statistical evidence for association. Upon covariate adjustment for smoking and gender, in the pooled German-Austrian AgP sample, IL10 SNP rs6667202 was associated with p = 0.016, OR = 0.77 (95% CI = 0.6-0.95), and in the Dutch AgP sample, adjacent IL10 SNP rs61815643 was associated with p = 0.0009, OR = 2.31 (95% CI = 1.4-3.8). At rs61815643, binding of the transcription factor PPARG was predicted. ANRIL rs1333048 was associated in the Turkish sample (pallelic = 0.026, OR = 1.67 [95% CI = 1.11-2.60]). CONCLUSIONS Previous candidate genes carry no susceptibility factors for AgP. Association of IL-10 rs61815643 with AgP is suggested. ANRIL is associated with periodontitis across different populations.

Effects of a Hydroxyapatite-based Biomaterial on Gene Expression in Osteoblast-like Cells

Biostite® is a hydroxyapatite-derived biomaterial that is used in periodontal and bone reconstructive procedures due to its osteoconductive properties. Since the molecular effects of this biomaterial on osteoblasts are still unknown, we decided to assess whether it may specifically modulate osteoblast functions in vitro. We found that a brief exposure to Biostite® significantly reduced the proliferation of MG-63 and SaOS-2 osteoblast-like cells to ~ 50% of the plateau value. Furthermore, gene array analysis of MG-63 cells showed that Biostite® caused a differential expression of 37 genes which are involved in cell proliferation and interaction, and related to osteoblast differentiation and tissue regeneration. Results were confirmed by RT-PCR, Western blot, and by an increase in alkaline phosphatase (ALP) specific activity. Biostite® also increased levels of polycystin-2, a mechano-sensitive Ca2+ channel, a promising new marker of bone cell differentiation. Biostite®, therefore, may directly affect osteoblasts by enhancing chondro/osteogenic gene expression and cytoskeleton-related signaling pathways, which may contribute to its clinical efficacy.

Ridge dimensions of the edentulous posterior maxilla: a retrospective analysis of a cohort of 127 patients using computerized tomography data

OBJECTIVES to evaluate the edentulous ridge dimensions of maxillary posterior sextants with a tridimensional radiographic technique. The influence of the presence/absence of teeth adjacent to the edentulous site on the dimensions of the edentulous ridge was also evaluated. MATERIAL AND METHODS computerized tomography (CT) scans of 127 patients (65 males and 62 females; mean age: 55.2 ± 10.1 years) with at least one missing tooth in the maxillary posterior sextants were analyzed. On CT cross sections, bone height (BH), bone width (BW) at 1, 3, and 7 mm from the most coronal point of the alveolar crest (BW(1 mm) , BW(3 mm) , and BW(7 mm) , respectively) and the relative vertical ridge position (rVRP) were assessed at the first premolar, second premolar, first molar and second molar edentulous sites. RESULTS the results of the study indicate that (i) the maxillary sinus was radiographically evident in about 50% of first premolar sites and 90-100% of second premolar and molar sites; (ii) BH showed a significant decrease from first premolar to molar sites; (iii) BW(1 mm) was higher at second molar site compared with the first and second premolar sites, BW(3 mm) and BW(7 mm) were higher at each molar site compared with each premolar site; (iv) the proportion of sites with BH ≥ 8mm and BWI mm ≥ 6mm was 28.3%, 18.4%, 8.0% and 18.2% [corrected] at first premolar, second premolar, first molar and second molar sites, respectively. The absence of teeth adjacent to the edentulous site negatively affected rVRP, but not BH and BW. CONCLUSIONS The results of the study indicate that at premolar and molar sites, [corrected] the dimensions of the alveolar crest may call for bone augmentation procedures for proper implant placement in a substantial amount of edentulous patients. When both mesial and distal tooth adjacent to the edentulous site are absent, the placement of implants of adequate dimensions may be more challenging due to a more apical position of the alveolar ridge compared with sites where both adjacent teeth are present.

Human herpesvirus 7, Epstein-Barr virus and human cytomegalovirus in periodontal tissues of periodontally diseased and healthy subjects.

AIMS To evaluate (i) the presence of human herpesvirus 7 (HHV-7), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV), and (ii) the transcription pattern of HHV-7 in gingival biopsies from patients affected by periodontitis (P) and periodontally healthy subjects (H). MATERIAL AND METHODS Thirty-seven subjects (P: n=24; H: n=13) were included. Each P patient contributed two gingival biopsies (representative of a clinically affected and non-affected site) and each H subject contributed one gingival biopsy. After DNA extraction, nested polymerase chain reaction was used to identify the viruses. RESULTS HHV-7 was detected in 91.7% of P patients and in 61.5% of H subjects (p=0.02), EBV in 50.0% samples of P patients and 7.7% of H subjects (p=0.005) and HCMV only in one sample from H group. EBV was more frequently detected in biopsies from affected sites (50.0%) than from non-affected sites (16.7%) (p=0.008). HHV-7 transcription was detected in 15.4% of affected and 15.4% of non-affected sites. CONCLUSIONS The results indicate that (i) gingival tissues can be considered a potential reservoir for HHV-7; (ii) when present, HHV-7 persists in a latent state in the majority of cases; (iii) the presence of EBV seems to be associated with the diseased state of the patient and site.

Root Coverage Esthetic Score After Treatment of Gingival Recession: An Interrater Agreement Multicenter Study

BACKGROUND The root coverage esthetic score (RES) system was proposed for evaluating esthetic outcomes of root coverage procedures. The aim of this multicenter study is to assess the interrater agreement of the RES among expert periodontists. METHODS Eleven periodontists were selected in different clinical centers. Each operator had ≥15 years of experience in mucogingival surgery. Each periodontist was trained to use RES before the beginning of the study. Subsequently, baseline and post-treatment (6 months) photographs of 41 Class I and II gingival recessions in 41 patients were separately given to each operator who evaluated the outcomes according to the RES method. A two-way random interclass correlation coefficient and 95% confidence interval (CI) were used to assess the global interrater agreement for RESs. RESULTS The total interrater agreement for RESs was 0.92 (95% CI: 0.88 to 0.95), which indicated that an almost perfect agreement was achieved. CONCLUSION Tested individually by a group of periodontists, the RES seems to be a reliable method for assessing the esthetic outcomes of root coverage procedures.

Soft tissues around long-term platform switching implant restorations: a histological human evaluation. Preliminary results.

BACKGROUND Switching platform restorations seems to reduce the peri-implant bone resorption and to preserve the peri-implant soft tissues. AIM The aim of the present human study was to compare histologically the peri-implant soft tissue in switching and traditional platform implants 4 years after restoration. MATERIALS AND METHODS Forty-eight months after implant restoration, 37 peri-implant soft tissue samples from 14 patients were harvested from traditionally restored implants (control group) and from three different platforms mismatching 0.25-0.85 mm (test groups). At the harvesting time, all sites were clinically healthy. Samples were processed to evaluate the inflammatory infiltrate area [inflamed connective tissue (ICT)], the microvascular density (MVD) and the collagen content (AA%). RESULTS At the analyses, no significant differences were found between groups in terms of ICT, MVD and AA% (p>0.05). In all groups, most samples with a well-preserved junctional epithelium showed a small and localized inflammatory infiltrated associated with not-well-oriented collagen fibres and an increased MVD. CONCLUSIONS Forty-eight months after restoration, switching and traditional platform implants had similar histological peri-implant soft tissue features, despite different bone level changes detected radiographically and published in a previous parent study. The present study seems to confirm platform switching as a safe prosthetic concept leading to better maintenance of peri-implant bone levels. However, further histological studies are required to longitudinally confirm the present data.