Controlled-release of rhBMP-2 carriers in the regeneration of osteonecrotic bone

Untreated osteonecrosis of the hip causes collapse of the femoral head and eventually leads to the development of premature degenerative arthritis. In order to reverse this late complication after the core decompression procedure, we studied three different types of carriers used to entrap recombinant human bone morphogenetic protein-2 (rhBMP-2) in terms of their performance in osteonecrosis regeneration and creeping substitution in Balb/C mice. The rhBMP-2 was loaded into PLGA-HAp microsphere in three different ways. We first verified the therapeutic dose in vitro using D1 and C2C12 cells. Then the individual performance of the three carrier preparations in vivo was examined by soft X-ray observation, histological analysis and immunostaining of bone tissue. In addition, the BMP-2 protein concentration activity in the serum was monitored. The results revealed that the bioactivity of rhBMP-2 released from a carrier with an ideal therapeutic dose was well maintained; this eventually helped to improve the healing and substitution of necrotic bone in vivo. These observations demonstrate that the in vivo performance of these newly developed rhBMP-2 delivery carriers correlates well with their in vitro release profiles. We concluded that sustained controlled-release of rhBMP-2 above a therapeutic dose could not only induce early callus wrapping of the necrotic bone but also produce neovascularization and substitution inside of the dead bone.