This Phase I project proposes to evaluate a novel methodology to induce biomimetic calcium phosphate (CaP) deposition on a chemically stable and covalently linked monolayer of a biomolecule, that induces hydroxyapatite (HA) nucleation in many biological process as well as on metallic implant surfaces. Because the coated biomolecules biomimetically induce the optimal hydroxyapatite depostion, this will in turn favorably affect the differentiation and growth of osteoblasts from their progenitors, the HEPM cells. Since the biomimetic molecular coating will be bound to metal by a stable chemical bonding mechanism, the bonding strength at metal-tissue interface will be enhanced. Thus, it is proposed to covalently immobilize a polymerizable linker functionality on Ti surface. On the other hand, a polymerizable monomer biomolecule will be synthesized, characterized and will be crosslinked covalently to the linker functionality on Ti surface. The modified surface will be tested for HA deposition and for adhesion strength of the HA formed, after they are incubated in contact with simulated body fluid. The experimental titanium implant samples, coated with the covalently bonded biomolecule will also be evaluated for their effects on osteoblast differentiation, metabolism and growth, as measured by osteoblast cell counts and the alkaline phosphatase specific activity. The data obtained from this study will contribute to the development of an alternative coating for optimum HA deposition and in turn will be valuable for further research on bone regeneration. In short, the novel surface modification in this proposal will contribute to the development of ideal coating properties for orthopedic implants with biomimetically formed thin apatite layer that will have superior coating-substrate interfacial strength, better osteoblast differentiation, metabolism, growth, and the formation of proteinaceous matrix, and in turn a better osseointegration, as compared to the currently available plasma sprayed HA-coated implants. This research is directed to reduce implant failures, which are costly to patients in implant cost, surgery cost, trauma and time. More than 500,000 bone related prostheses are placed annually in the US. A total of 11% of these, end up in failure in an average time of 10 years. Estimated annual medical care costs for implant failures is $15 billion, and total costs (medical care plus lost productivity) are estimated at $65 billion, besides the immense pain and suffering to the patients. This project has a potential for a biomimetic fixation of implant-bone interface, and therefore, its better osseointegration compared to the currently available commercial implants. ? ? ?
