Bone inductive properties of rhBMP-2 loaded porous calcium phosphate cement implants in cranial defects in rabbits

Abstract

In this study, the osteoinductive properties of porous calcium phosphate (Ca-P) cement loaded with bone morphogenetic protein 2 (rhBMP-2) were evaluated and compared with rhBMP-2 loaded absorbable collagen sponge (ACS). Discs with a diameter of 8 mm were loaded with a buffer solution with or without 10 μg rhBMP-2 and inserted in 8 mm full thickness cranial defects in rabbits for 2 and 10 weeks of implantation. Histological analysis revealed excellent osteoconductive properties of the Ca-P material. It maintained its shape and stability during the implantation time better than the ACS but showed no degradation like the ACS. Quantification of the Ca-P cement implants showed that bone formation was increased significantly by administration of rhBMP-2 (10 weeks pore fill: 53.0±5.4%), and also reached a reasonable amount without rhBMP-2 (43.1±10.4%). Remarkably, callus-like bone formation outside the implant was observed frequently in the 2 weeks rhBMP-2 loaded Ca-P cement implants, suggesting a correlation with the presence of growth factor in the surrounding tissue. However, an additional in vitro assay revealed an accumulative release of no more than 9.7±0.9% after 4 weeks. We conclude that: (1) Porous Ca-P cement is an appropriate candidate scaffold material for bone engineering. (2) Bone formation can be enhanced by lyophilization of rhBMP-2 on the cement. (3) Degradation of porous Ca-P cement is species-, implantation site- and implant dimension-specific.