Enhanced bone formation using hydroxyapatite ceramic coated with fibroblast growth factor-2

Our objective was to develop a bone substitute coated with fibroblast growth factor-2 (FGF-2) that subsequently releases FGF-2. We investigated the use of our system of bone substitutes to induce bone formation. Hydroxyapatite ceramic buttons (HAP-CBs) were coated with FGF-2 by precipitation in supersaturated calcium phosphate solution. HAP-CBs were coated with high or low doses of FGF-2, denoted as FGF-H and FGF-L. The release of FGF-2 from FGF-H and FGF-L was evaluated using its release profile and bioactivity. The efficacy of the subsequent bone formation was quantified using rats with round-shaped bone defects (5 mm in diameter) of the right parietal bone. Group 1 was treated only with HAP-CBs, group 2 with HAP-CBs and drops of FGF-2 solution, group 3 with FGF-L and group 4 with FGF-H. To detect the release of FGF-2 in vivo, the expression of bone morphogenic protein-2 (BMP-2) was measured in the defective bone tissue. FGF-2 was released in vitro from FGF-H and FGF-L, and maintained its bioactivity. Rats treated with FGF-L showed better bone formation than rats from the other groups. BMP-2 expression was detected in the defective bone tissues of group 3 at 14 days, which might indicate in vivo FGF-2 release during this period. A specific FGF-2 concentration may be needed for bone formation, and our system can release FGF-2 at adequate concentrations to induce bone formation.