Effects of low-dose rhBMP-2 on peri-implant ridge augmentation in a canine model.

AIMS: The aim of this study was to investigate the potential of low-dose rhBMP-2 combined with Hydroxyapatite (HAp)/ß-tricalcium phosphate (TCP)/ Collagen (Col) composite in repairing the peri-implant critical size defect and to determine the optimal rhBMP-2 concentration. MATERIALS AND METHODS: Fifty saddle-type alveolar defects (10 mm mesiodistally and 4 mm apicocoronally) were surgically prepared on edentulous ridges in ten beagle dogs. Following implant placement, the defects with vertically exposed implant fixtures either received (a) no graft, (b) HAp/TCP/Col composite, (c) HAp/TCP/Col +0.02 mg/ml rhBMP-2, (d) HAp/TCP/Col +0.08 mg/ml rhBMP-2 or (e) HAp/TCP/Col +0.2 mg/ml rhBMP-2. After healing for 4 or 8 weeks, bone regeneration and mineralization were assessed through radiography, micro-CT, fluorescence labelling and histologic analyses. Implant stability was measured through resonance frequency analysis. RESULTS: It was evident HAp/TCP/Col with 0.2 mg/ml rhBMP-2 manifested strong osteogenic potential in this large animal model, as significantly more and faster new bone formation with better implant stability was identified compared to the HAp/TCP/Col-alone control group (adjusted p < .05). CONCLUSIONS: Our results highlight the constructs of HAp/TCP/Col +0.2 mg/ml rhBMP-2 without barrier membranes as a promising tool for peri-implant ridge augmentation.

Preliminary evaluation of BMP-2-derived peptide in repairing a peri-implant critical size defect: A canine model.

BACKGROUND/PURPOSE: A synthetic bone morphogenetic protein (BMP)-2-derived peptide has been discovered to promote bone regeneration. The present study investigated the potential of the BMP-2 peptide combined with hydroxyapatite (HAp)/ß-tricalcium phosphate (TCP)/collagen (Col) composite in repairing a peri-implant critical size defect. METHODS: Twenty-four saddle-type alveolar defects (10 mm mesiodistally and 4 mm apicocoronally) were surgically prepared in edentulous ridges in four male beagle dogs. Following implant placement, the defects with vertically exposed implant fixtures received (a) HAp/TCP/Col composite, (b) HAp/TCP/Col + 4 mg/mL BMP-2 peptide, (c) HAp/TCP/Col + 20 mg/mL BMP-2 peptide, or (d) HAp/TCP/Col + 0.2 mg/mL recombinant human BMP-2 (rhBMP-2). Bone regeneration and mineralization were assessed using radiography, micro-computed tomography (micro-CT), fluorescence labeling, and histologic analyses after healing for 4 or 8 weeks. Implant stability was measured using resonance frequency analysis. RESULTS: The 20 mg/mL BMP-2 peptide groups demonstrated a distinguishable advantage in bone regeneration potential over the control groups, as observed on radiographic imaging and histologic examination, although no significant difference was found in implant stability and histomorphometric analysis of mineralization levels. However, the performance of the 20 mg/mL BMP-2 peptide groups were inferior to that of the 0.2 mg/mL rhBMP-2 groups. CONCLUSION: The BMP-2 peptide may accelerate peri-implant bone regeneration. The BMP-2 peptide at 20 mg/mL still cannot complete bone repair of peri-implant critical size defect. The BMP-2 peptide at 20 mg/mL has similar osteoinductive performance to the rhBMP-2 at 0.02 mg/mL.

Simvastatin suppresses osteoblastic expression of Cyr61 and progression of apical periodontitis through enhancement of the transcription factor Forkhead/winged helix box protein O3a.

INTRODUCTION: In this study, the role of transcription factor Forkhead/winged helix box protein O3a (FoxO3a) in Cyr61 expression and its modulation by simvastatin were investigated in cultured murine osteoblasts and a rat model of induced apical periodontitis. We also examined the effects of simvastatin on the synthesis of chemokine CCL2 and chemotaxis of macrophages in vitro. METHODS: We assessed tumor necrosis factor (TNF)-α-stimulated expression of Cyr61 and phosphorylated inactive FoxO3a (p-FoxO3a) in MC3T3-E1 murine osteoblasts by Western analysis. Forced expression of FoxO3a by lentiviral-based gene transduction was performed, and its effect on Cyr61 expression was evaluated. The modulation of CCL2 secretion and macrophage chemotaxis by simvastatin were examined by enzyme-linked immunosorbent assay and transwell migration assay, respectively. In a rat model of induced apical periodontitis, the relation between disease progression and osteoblastic expression of Cyr61, p-FoxO3a, and CCL2 and macrophage recruitment were studied by radiographic and immunohistochemistry analyses. RESULTS: Western blot analysis showed enhanced expression of Cyr61 and p-FoxO3a after TNF-α treatment in a time-dependent manner. Simvastatin significantly counteracted the actions of TNF-α. Forced expression of FoxO3a reduced TNF-α-stimulated Cyr61 synthesis. Simvastatin and FoxO3a diminished TNF-α-induced CCL2 secretion and macrophage recruitment, whereas Cyr61 partially restored the stimulating action. In rat periapical lesions, simvastatin significantly attenuated bone resorption, reduced osteoblastic expressions of Cyr61, p-FoxO3a, and CCL2, and suppressed macrophage recruitment. CONCLUSIONS: Simvastatin may alleviate periapical lesions by enhancing FoxO3a activity to suppress the synthesis of Cyr61 in osteoblasts. Moreover, the downstream effector mechanism of Cyr61 may involve CCL2 production and macrophage recruitment.

Meta-regression analysis of the initial bone height for predicting implant survival rates of two sinus elevation procedures.

AIM: To undertake a systematic review for the association between the initial alveolar bone height and the success of dental implants with sinus elevation procedures. MATERIALS AND METHODS: An online search was performed using the following electronic databases: PubMed, Medline, Science Direct, and Blackwell synergy. Two investigators independently assessed publications for inclusion and extracted data. Meta-regression analyses were used to test the associations between the initial alveolar bone height and implant survival with lateral window or osteotome sinus elevation procedures. RESULTS: Of 635 studies, 21 were included for analysis. A quadratic curve-fitting meta-regression showed an increasing trend of implant survival rate with greater initial bone height for the lateral window technique (p<0.0001, adjusted R(2)=0.97). The result of the meta-regression for hazard rates showed a decreasing trend (p=0.0041, adjusted R(2)=0.89). No association was found for the osteotome technique. CONCLUSIONS: For the lateral window technique, meta-regression analysis suggested a positive association between the initial alveolar bone height and implant survival rates. No relationship was found between the initial alveolar bone height and implant survival rate for the osteotome technique due to a lack of data below 4 mm of initial bone height.