Ectopic osteoinduction and early degradation of recombinant human bone morphogenetic protein-2-loaded porous β-tricalcium phosphate in mice

The present study investigated the ectopic osteoinduction and early degradation of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded porous beta-tricalcium phosphate (β-TCP) in mice. The porous β-TCP with 50 μg of rhBMP-2 (n=25n=25) and porous β  -TCP (control group, n=25n=25) were implanted into muscle pouches in the right and left thigh of 28-day-old mice (n=25n=25), respectively. At every time point (3, 7, 14, 21 and 28 days after implantation), five mice were euthanized and the histological examinations of implantation sites were performed. In addition, the alkaline phosphatase (ALP) activity was also quantitatively analyzed. For the rhBMP-2-loaded group, blood vessel formation and immature cartilage was observed within the porous β-TCP 3 days after implantation. Mature cartilage was observed 7 days after implantation of rhBMP-2-loaded porous β-TCP. Newly formed woven bone, lamellar bone as well as marrow were observed 14 and 21 days after implantation of the rhBMP-2-loaded porous β-TCP. Lamellar bone and marrow were observed 28 days after implantation of the rhBMP-2-loaded porous β-TCP. For the control group, no bone or cartilage was observed at all time points. However, multinucleated giant cells and fibrous tissues were observed in the control group at 7 and 28 days after implantation, respectively. At 21 and 28 days after implantation, porous β-TCP was observed to fragment indicating early degradation of the porous β-TCP in both groups. In addition, ALP was observed to be significantly higher in the rhBMP-2-loaded β-TCP as compared to the control β-TCP. It was concluded from this study that the rhBMP-2-loaded porous β-TCP induced blood vessel and ectopic bone formation.