The Experimental Study On Bone Regeneration Around Dental Implant With Dual Growth Factor Delivery

Background:Sufficient bone volume is required for dental implant placement, especially for immediate implant. Numerous methods of augmentation for the deficient alveolar ridge in an immediate implant placement have been reported. Autologous bone grafting is associated with limited availability of harvest bone and donor site morbidity. The major disadvantages of allografts are the potential of disease transmission and prolonged healing at the graft-host interface. As synthetic scaffold is easily acquired and free of pathogenic disease transmission, a 3-D scaffold for multi-gene delivery to mimic natural biological processes of bone healing is a potential candidate approach for bone regeneration.Objective: The purpose of this study was to explore an optimal delivery system of VEGF and BMP-2 gene and observe their synergetic potential of promoting bone healing in bone defects around dental implants.Material and Methods:Five groups of scaffold were fabricated by a freeze-drying method, including pure chitosan/collagen scaffold; scaffold loaded with adenoviruses expressing BMP-2, adenoviruses expressing VEGF, both adenoviruses expressing BMP-2 and adenoviruses expressing VEGF, VEGF protein and adenovirus expressing BMP-2. In vitro studies examined whether BMSCs were responsive to these scaffolds over time. Bone formation capacity, bone-to-implant contact, as well as removal torque values were investigated in vivo.Results:Chitosan/collagen scaffolds were functioned with adenoviral vectors expressing BMP-2 and VEGF, or an adenoviral vector expressing BMP-2 and VEGF protein. In vitro study showed that these scaffolds exhibited good biocompatibility. Moreover, scaffolds expressing BMP-2 showed a stronger differentiation towards the osteoblast phenotype. A burst and rapid release of VEGF was seen in scaffold combined with VEGF protein and an adenoviral vector encoding BMP-2, while a sustained expression of VEGF and BMP-2 was seen in scaffold combined with adenovirus vectors encoding corresponding gene. In vivo study of defects around dental implants showed exogenous expression of VEGF alone has no impact on bone regeneration at 4 and 8 weeks. Enhanced bone formation was found at 4 and 8 weeks with scaffolds expressing BMP-2. Furthermore, VEGF protein combined with Ad-BMP-2 represented the best outcomes. Significantly higher removal torque values were also observed in these two groups by removal torque measurement at 12 weeks. Conclusions:A combination of BMP-2 gene and VEGF protein could have a synergistic effect in promoting bone healing.