This proposal describes a five-year training program for the development of a clinician-scientist. This collaborative research effort is intended to provide a stimulating training environment for the PI who is a fully trained orthopedic surgeon specializing in joint reconstruction. The proposal integrates internationally recognized investigators from various disciplines (Biochemistry, Bioengineering, Materials Science, Molecular Biology, Cell Biology, and Orthopedic Surgery) to use their expertise in training the PI and to address a pressing clinical problem. Despite extensive and effective measures, periprosthetic infection continues to affect 1-5 percent of joint replacements. With over 600,000 joint replacements being performed annually in the US and an expected rise in this number to exceed 1 million by the year 2030, periprosthetic infection poses a substantial economic and psychological burden to the healthcare and the patients. The objective of this research proposal is to develop a 'smart'prosthesis that addresses this important problem. Adhesion peptides (RGD) and antibiotic (Linezolid) will be linked directly to the surface of the titanium (Ti) implant to promote osseointegration and, on-demand, to control infection. In addition, the Ti will be covered with a thin, soluble sol-gel film that will release antibiotics to eradicate bacterial infections. The efficacy of the """"""""smart"""""""" implant will be tested in a dog model to evaluate its bactericidal and osteogenic potential. The combination of early release and durable tethered antibiotic on the surface of the implant provides an effective antibacterial milieu around the hip that can minimize the incidence of early and late infections. The development of this technology will address a real need in orthopedic surgery in treating two of the most dreaded complications of arthroplasty, namely periprosthetic infection and osteolysis. As a result, patient pain, suffering and morbidity will be minimized.
