Comparative study of BMP-2 alone and combined with VEGF carried by hydrogel for maxillary alveolar bone regeneration

The effect of vascular endothelial growth factor (VEGF) combined with bone morphogenetic protein-2 (BMP-2) for bone regeneration is still controversial as to whether or not VEGF has a synergistic or additive effect. This study attempted to evaluate the synergistic effect of VEGF and BMP-2 compared to BMP-2 alone for maxillary alveolar bone regeneration using collagen sponge/hydrogel complex sheets in a canine model. After mixing BMP-2 and VEGF with a hyaluronic acid-based hydrogel (HAH), the collagen sponge/hydrogel complex was transplanted into maxillary alveolar bone defects (n=14) after the extraction of canine upper first molars on both sides. Bone regeneration was evaluated in three groups (control group without growth factors, experimental groups I and II with BMP-2 alone and BMP-2 and VEGF, respectively) using micro-computed tomography and histological staining. The total amount of new bone formations and bone mineral density were significantly higher in the group with BMP-2 only and the group with BMP-2 combined with VEGF than it in the control group. The area with positive staining of von Willebrand factor bone defect was significantly greater in the group with BMP-2 only and with dual growth factors than the control. BMP-2 released from the HAH promoted new bone formation. However, the combination of BMP-2 and VEGF did not show a synergistic or additive effect on bone regeneration at canine maxillary alveolar bone defects.