Enhanced bone regeneration around dental implant with bone morphogenetic protein 2 gene and vascular endothelial growth factor protein delivery

Abstract

To evaluate the synergistic effect of bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) on the repair of bone defects around dental implants. 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 VEGF, VEGF protein and adenovirus expressing BMP-2. In vitro studies examined whether bone marrow stromal cells were responsive to these scaffolds over time. Bone formation capacity, bone-to-implant contact, as well as removal torque values were investigated in vivo. Differences between the various groups were statistically analyzed using the one-way analysis of variance test. The in vitro study revealed a burst and rapid release of VEGF with a sustained high-level expression of BMP-2 in scaffold combined with VEGF protein and adenoviruses expressing BMP-2. Histomorphometry demonstrated that scaffolds expressing BMP-2 enhanced more bone formation compared with other groups; VEGF alone is insufficient to promote bone formation. New bone formation in the bone defects around dental implants, bone-to-implant contact and mean peak removal torque showed statistically significant difference for the adenoviral vector encoding human bone morphogenetic protein 2 (Ad-BMP-2) and VEGF protein and adenovirus expressing BMP-2 groups. Furthermore, scaffold combined with VEGF protein and Ad-BMP-2 represented the best outcomes in this model. A combination of BMP-2 gene and VEGF protein could have a synergistic effect in promoting bone healing.