Effect of Control-released Basic Fibroblast Growth Factor Incorporated in β-Tricalcium Phosphate for Murine Cranial Model

Background: beta-Tricalcium phosphate (beta-TCP) is used clinically as a bone substitute, but complete osteoinduction is slow. Basic fibroblast growth factor (bFGF) is important in bone regeneration, but the biological effects are very limited because of the short half-life of the free form. Incorporation in gelatin allows slow release of growth factors during degradation. The present study evaluated whether control-released bFGF incorporated in beta-TCP can promote bone regeneration in a murine cranial defect model. Methods: Bilateral cranial defects of 4 mm in diameter were made in 10-week-old male Sprague-Dawley rats treated as follows: group 1, 20 mu l saline as control; group 2, beta-TCP disk in 20 ae l saline; group 3, beta-TCP disk in 50 mu g bFGF solution; and group 4, beta-TCP disk in 50 mu g bFGF-containing gelatin hydrogel (n = 6 each). Histological and imaging analyses were performed at 1, 2, and 4 weeks after surgery. Results: The computed tomography value was lower in groups 3 and 4, whereas the rate of osteogenesis was higher histologically in group 4 than in the other groups. The appearance of tartrate-resistant acid phosphatepositive cells and osteocalcin-positive cells and disappearance of osteopontin- positive cells occurred earlier in group 4 than in the other groups. Conclusions: These findings suggest that control-released bFGF incorporated in beta-TCP can accelerate bone regeneration in the murine cranial defect model and may be promising for the clinical treatment of cranial defects.