BMP-2 Releasing Implant Surface for Bone Regeneration

DESCRIPTION (provided by applicant): The proposed study will evaluate the efficacy of a short chain, biodegradable spacer as a delivery mechanism for a bone regenerative protein on titanium (Ti) implant surface. Our overall hypothesis is that the covalent binding of BMP-2 on a implant surface for its controlled release on wound site will directly affect early bone induction. The objectives of this study are 1) to couple BMP-2 on Ti surface by the linkers consisting of 6-12 atom chains having the same monomeric functionalities as that of a few biodegradable polymers, such as poly-lactic acid, poly-glycolic acid, poly-hydroxy butyrate, so that the linker may retain the property of biodegardation, yet does not inherit the side effect of residue accumulation as a result of incomplete degradation. 2) to investigate the efficiency of the said linker as a delivery system for BMP-2 in the cell conditioned culture medium, and 3) to correlate the effect of implants material covalently bound with BMP-2 with early maturation of bone cells in-vitro. In this proposal, aim-1 will evaluate the relative efficiency of the aforesaid linkers as a delivery mechanism for the bone regenerative protein by measuring the release rate of protein from the Ti surface. We will first modify the Ti surface by an amino terminating chemical entity, which will then be coupled with to the amino terminus of BMP-2 through a short chain linker having biodegradable functionality. The protein bound Ti surface will then be immersed in a cell conditioned culture medium. A radioactive version of the surface modification will also be made, using tritium labeled linker and the release of the protein over time will be measured conveniently. Aim 2 will determine the extent to which the BMP-2 modified imptant surface effects osteobtast proliferation, differentiation, and metabolism in vitro. Data generated will provide information oil a novel coating useful as a delivery mechanism for BMP-2 and the effect on the novel coating on eady maturation of bone cells. Additionally, the information generated will contribute to development of an ideal biomimetic and biocompatible implant material, thereby reducing long-term implant failures.