Clinical applications of cell-based approaches in alveolar bone augmentation: a systematic review.

BACKGROUND: Cell-based approaches, utilizing adult mesenchymal stem cells (MSCs), are reported to overcome the limitations of conventional bone augmentation procedures. PURPOSE: The study aims to systematically review the available evidence on the characteristics and clinical effectiveness of cell-based ridge augmentation, socket preservation, and sinus-floor augmentation, compared to current evidence-based methods in human adult patients. MATERIALS AND METHODS: MEDLINE, EMBASE, and CENTRAL databases were searched for related literature. Both observational and experimental studies reporting outcomes of "tissue engineered" or "cell-based" augmentation in ≥5 adult patients alone, or in comparison with non-cell-based (conventional) augmentation methods, were eligible for inclusion. Primary outcome was histomorphometric analysis of new bone formation. Effectiveness of cell-based augmentation was evaluated based on outcomes of controlled studies. RESULTS: Twenty-seven eligible studies were identified. Of these, 15 included a control group (8 randomized controlled trials [RCTs]), and were judged to be at a moderate-to-high risk of bias. Most studies reported the combined use of cultured autologous MSCs with an osteoconductive bone substitute (BS) scaffold. Iliac bone marrow and mandibular periosteum were frequently reported sources of MSCs. In vitro culture of MSCs took between 12 days and 1.5 months. A range of autogenous, allogeneic, xenogeneic, and alloplastic scaffolds was identified. Bovine bone mineral scaffold was frequently reported with favorable outcomes, while polylactic-polyglycolic acid copolymer (PLGA) scaffold resulted in graft failure in three studies. The combination of MSCs and BS resulted in outcomes similar to autogenous bone (AB) and BS. Three RCTs and one controlled trial reported significantly greater bone formation in cell-based than conventionally grafted sites after 3 to 8 months. CONCLUSIONS: Based on limited controlled evidence at a moderate-to-high risk of bias, cell-based approaches are comparable, if not superior, to current evidence-based bone grafting methods, with a significant advantage of avoiding AB harvesting. Future clinical trials should additionally evaluate patient-based outcomes and the time-/cost-effectiveness of these approaches.

Genomic analyses of early peri-implant bone healing in humans: a systematic review.

OBJECTIVE: The objective of the study was to systematically review the literature for studies reporting gene expression analyses (GEA) of the biological processes involved in early human peri-implant bone healing. METHODS: Electronic databases (MEDLINE, EMBASE) were searched in duplicate. Controlled and uncontrolled studies reporting GEA of human peri-implant tissues - including ≥5 patients and ≥2 time points - during the first 4 weeks of healing were eligible for inclusion. Methodological quality and risk of bias were also assessed. RESULTS: Four exploratory studies were included in reporting GEA of either tissues attached to SLA or SLActive implants after 4 to 14 days or cells attached to TiOBlast or Osseospeed implants after 3 to 7 days. A total of 111 implants from 43 patients were analyzed using validated array methods; however, considerable heterogeneity and risk of bias were detected. A consistent overall pattern of gene expression was observed; genes representing an immuno-inflammatory response were overexpressed at days 3 to 4, followed by genes representing osteogenic processes at day 7. Genes representing bone remodeling, angiogenesis, and neurogenesis were expressed concomitantly with osteogenesis. Several regulators of these processes, such as cytokines, growth factors, transcription factors, and signaling pathways, were identified. Implant surface properties seemed to influence the healing processes at various stages via differential gene expression. CONCLUSION: Limited evidence from gene expression studies in humans indicates that osteogenic processes commence within the first post-operative week and they appear influenced at various stages by implant surface properties.

Volume changes of maxillary sinus augmentations over time: a systematic review.

PURPOSE: The objective of this study was to systematically review the available literature on three-dimensional time-dependent graft volume changes after sinus augmentation (SA) with different biomaterials in humans. MATERIALS AND METHODS: MEDLINE, EMBASE, and CENTRAL were searched for related literature. Controlled and uncontrolled studies reporting volume changes of more than 10 SAs after at least 6 months, assessed by computed tomography (CT) or cone beam CT (CBCT), were eligible for inclusion. The primary outcome of interest was time-dependent percentage change in augmentation volume. RESULTS: Seven controlled and five uncontrolled studies (n = 234 SAs) with a high risk of bias were included and reported on a range of graft materials. Autogenous bone (AB) was used in the particulate or block form. Bone substitutes (BS) were used either alone or in combination with other materials as composite grafts (CG). All studies reported reductions in augmentation volumes over time (AVR), generally after short observation periods (range, 6 months to 6 years). Substantial AVRs (approximately 45% in 77 SAs) were reported for AB after 6 months and up to 2 years. AVRs for solely BS or CG were relatively lower (approximately 18% to 22% in 142 SAs) after a similar time period. All studies reported a wide range of volume reductions. No significant differences in AVR were observed between different graft materials. Because of insufficient long-term data, a reliable association between volume reduction and time could not be established. CONCLUSION: Some loss of augmentation volume always occurs after SA during early healing times. In general, less AVR may be expected after SA with BS or CG compared to SA with AB. Augmentation volume loss does not seem to compromise implant placement or survival.

Cone-beam computed tomographic analysis of sinus membrane thickness, ostium patency, and residual ridge heights in the posterior maxilla: implications for sinus floor elevation.

OBJECTIVE: To determine, using cone-beam computed tomography (CBCT), the residual ridge height (RRH), sinus floor membrane thickness (MT), and ostium patency (OP) in patients being evaluated for implant placement in the posterior maxilla. MATERIALS AND METHODS: CBCT scans of 128 patients (199 sinuses) with ≥1 missing teeth in the posterior maxilla were examined. RRH and MT corresponding to each edentulous site were measured. MT >2 mm was considered pathological and categorized by degree of thickening (2-5, 5-10 mm, and >10 mm). Mucosal appearance was classified as "normal", "flat thickening", or "polypoid thickening", and OP was classified as "patent" or "obstructed". Descriptive and bivariate statistical analyses were performed. RESULTS: MT >2 mm was observed in 60.6% patients and 53.6% sinuses. Flat and polypoid mucosal thickening had a prevalence of 38.1% and 15.5%, respectively. RRH ≤4 mm was observed in 46.9% and 48.9% of edentulous first and second molar sites, respectively. Ostium obstruction was observed in 13.1% sinuses and was associated with MT of 2-5 mm (6.7%), 5-10 mm (24%), and >10 mm (35.3%, P < 0.001). Polypoid mucosal lesions were more frequently associated with ostium obstruction than flat thickenings (26.7% vs. 17.6%, P < 0.001). CONCLUSION: Thickened sinus membranes (>2 mm) and reduced residual ridge heights (≤4 mm) were highly prevalent in this sample of patients with missing posterior maxillary teeth. Membrane thickening >5 mm, especially of a polypoid type, is associated with an increased risk for ostium obstruction. In the presence of these findings, an ENT referral may be beneficial prior to implant-related sinus floor elevation.

Association between periapical lesions and maxillary sinus mucosal thickening: a retrospective cone-beam computed tomographic study.

INTRODUCTION: Odontogenic infections are a common cause of maxillary sinusitis. This study aimed to evaluate the relationship between teeth with periapical lesions or periodontal disease and sinus mucosal thickening using cone-beam computed tomography (CBCT) imaging. METHODS: CBCT scans of 243 patients (485 sinuses) were evaluated retrospectively for the presence of periapical lesions and/or periodontal disease in posterior maxillary teeth and associated sinus mucosal thickening. Thickening >2 mm was considered pathological and was categorized by degree (2-5 mm, 5-10 mm, and >10 mm) and type (flat or polypoid). Descriptive, bivariate, and multivariate statistical analyses were performed. RESULTS: Mucosal thickening >2 mm was observed in 147 (60.5%) patients and 211 (44.6%) sinuses and was mostly of a "flat" type. Bivariate analysis revealed significant associations between mucosal thickening >2 mm and sex (males), age (>60 years), and teeth with periapical lesions and periodontal disease (P ≤ .027). Multivariate regression analysis identified only sex (males, odds ratio = 1.98, P = .004) and teeth with periapical lesions (odds ratio = 9.75, P < .001) to be associated with mucosal thickening >2 mm. CONCLUSIONS: Sinus mucosal thickening is a common radiographic finding, which is more likely to be observed in males (2×) and in relation to teeth with periapical lesions (9.75×).