VEGF-activated angiogenesis during bone regeneration.

PURPOSE: The aim of this study was to investigate the influence of controlled release of recombinant human vascular endothelial growth factor (rhVEGF(165)) on angiogenesis and osteogenesis in a mandibular defect model. MATERIAL AND METHODS: A total of 56 rabbits were operated and bicortical holes were placed at the lower border of the mandible. The defects were filled with type-I collagen, with collagen complexed with 0.8 mug rhVEGF(165), or left without any filling. After 3, 7, 14, and 28 days, specimens were taken and histologic, histomorphometric, and immunohistologic analyses were carried out concerning number of vessels, cross-sectional area of vessels, and area and density of regenerated bone. RESULTS: Bone formation occurred in a typical centripetal direction and showed all stages of bone regeneration and maturation. New vessel formation took place in front of the osteogenic regeneration front. The number of vessels increased in all groups until day 14, followed by physiologic regression in the control groups as opposed to persisting high numbers in the study group. The area of newly formed bone showed no difference to the control group but the density of regenerated bone was significantly higher in the study group. CONCLUSION: Blood vessels are an important component of bone formation and maintenance and the bone tissue differentiation is related to the local presence of blood vessels. The activation of angiogenesis using rhVEGF(165) leads to more intensive angiogenesis and bone regeneration.