Introduction of ectopic bone formation by BMP-2 incorporated biomimetically into calcium phosphate coatings of titanium-alloy implants

We have recently shown that proteins can be biomimetically co-precipitated with calcium phosphate crystals upon the surfaces of titanium-alloy implants. When recombinant human bone morphogenetic protein 2 (rhBMP-2) was thus incorporated into the inorganic matrix, it retained its bioactivity as an osteoinductive agent in vitro. Furthermore, the osteogenicity (alkaline phosphatase activity) of rat bone-marrow stromal cells grown on BMP-2-containing calcium phosphate coatings was higher than that of cells cultured on a plastic substratum and exposed to the freely-suspended drug. In the present study, titanium-alloy discs bearing BMP-2-containing calcium phosphate coatings were implanted ectopically (subcutaneously) in rats and the bone-formation process monitored during the ensuing 1-5 weeks. Osseous tissue appeared 2 weeks after implantation and thereafter increased steadily in mass. Hence, BMP-2 incorporated into the calcium phosphate coatings of titanium-alloy implants retains its bioactivity as an osteoinductive agent in vivo. The principle of this system may be put to good use in orthopaedic and dental implant surgery.