Enhancement of the osteogenic efficacy of osteoblast transplantation by the sustained delivery of basic fibroblast growth factor

Abstract

Previously, the sustained delivery of basic fibroblast growth factor (bFGF) has been demonstrated to promote bone regeneration in bone defects that had not been treated with osteogenic cell transplantation. In this study, we tested the hypothesis that the sustained delivery of bFGF could enhance osteoblast transplantation-mediated ectopic bone formation. Rat osteoblasts and bFGF were mixed with an injectable fibrin matrix and subcutaneously transplanted to rats (cell + bFGF group). The fibrin matrix played roles in both the cell transplantation matrix and the bFGF sustained delivery matrix. The transplantation of osteoblasts suspended in a fibrin matrix without bFGF served as a control. Twelve weeks after transplantation, histological analyses of retrieved transplants showed that new bone formation was more abundant and mature in the cell + bFGF group than in the control group. The bone formation area and the calcium content in the cell + bFGF group were two- and nine-fold higher, respectively, than those in the control group. Enhanced bone formation by the sustained delivery of bFGF may be attributed to the enhanced osteogenic gene expression of the transplanted cells and neovascularization of the transplants, as both mRNA expression of various osteogenic markers and arteriole density in the cell + bFGF group were significantly higher than those in the control group. This study demonstrates that the sustained delivery of bFGF can potentiate ectopic bone regeneration by osteoblast transplantation. This combination therapy may have effective implications for bone regeneration in large bone defects in which extensive osteogenic cell migration and angiogenesis are required.