BMP-2 Release and Dose-Response Properties of New HAp

Objective: The aim of this study is to investigate in vivo local BMP-2 PK and bone induction in three ceramics systems, based on different surface structures. Method: Cortical bones of bovine femur (Holstein, bull, Hokkaido, Japan) were used as starting materials for functionally graded Hydroxyapatite (fg-HAp) and bulk-HAp (b-HAp). Spongy and cortical bones in bovine femur were calcined at 800ºC by the step-wise calcinations to obtain b-HAp. The fg-HAp was designed by the partial dissolution-precipitation method. The fg-HAp ceramics were characterized by the pore sizes of 100~600µm, porosities of 70~80%, and small amounts of metal ions. SEM photographs of the fg-HAp showed spherical moss-like grains of about 1.0µm in size, which consisted of about 10-nm reprecipitated HAp (r-HAp) microcrystals. BMP-2 release study: We estimated the in vivo release profile of ¹²⁵I–labeled BMP-2 from fg-HAp, b-HAp and β-TCP (Osferion^®, Osaka, Japan). BMP-2 dose-response study: The fg-HAp, b-HAp and β-TCP containing 0.05, 0.1, 0.3, 0.5, 1.0, 5.0μg of BMP-2 were implanted into the back subcutis and evaluated induction of hard tissues histologically. Result: BMP-2 release study: BMP-2 was gradually released with time from three ceramics. The amount of BMP-2 remaining in the fg-HAp at 1 day after implantation was 83.8%, while the amount was 43.0% in the b-HAp and 49.6% in the β-TCP. BMP-2 dose-response study: Ectopic bone formation were found surely in the fg-HAp/BMP-2 (0.3μg) system at 3 weeks, whereas the minimal dose of BMP-2 for bone induction was 5.0μg and 0.5μg, in b-HAp/BMP-2 system and in β-TCP/BMP-2 system, respectively. Conclusion: Specific nano-micro structures and biodegradation of fg-HAp is more effective for both BMP-2 retention and bone induction, compared to b-HAp and β-TCP, in the ectopic model.