Basic fibroblast growth factor up-regulates the expression of vascular endothelial growth factor during healing of...

Recently we reported that basic fibroblast growth factor (bFGF) improved the healing of allogeneic bone grafts. However, the mechanism of action of the bFGF was not known. Therefore, the present study was designed to identify the expression pattern of vascular endothelial growth factor (VEGF) in the presence of bFGF reconstituted in demineralized intramembranous bone matrix (DBMIM) during the healing of allogeneic bone grafts. Eighteen critical size (15 mm x 10 mm) defects were created on rabbit mandibles bilaterally. Three groups of six defects each were grafted with allogeneic bone alone, allogeneic bone and DBMIM, and allogeneic bone and bFGF reconstituted in DBMIM. Three weeks later, the defects were retrieved for immunohistochemistry and in situ hybridization for VEGF. The percentage of positive staining area was quantified by using image analyzer. The increase (517%) in the expression of VEGF mRNA was accompanied by an increase (492%) of immunoreactive VEGF protein in allogeneic bone graft augmented by bFGF reconstituted in DBMIM. A close correlation existed between levels of VEGF production and the amount of newly formed bone. The results show that bFGF reconstituted in DBMIM markedly up-regulated the expression of VEGF in the grafted area. Basic FGF augments the healing of allogeneic bone grafts by enhancing vascularization through the up-regulation of VEGF.