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

BACKGROUND: β-Tricalcium phosphate (β-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 β-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 μl saline as control; group 2, β-TCP disk in 20 μl saline; group 3, β-TCP disk in 50 μg bFGF solution; and group 4, β-TCP disk in 50 μg 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 phosphate–positive 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 β-TCP can accelerate bone regeneration in the murine cranial defect model and may be promising for the clinical treatment of cranial defects.