Smart Substrates for a New Generation of Implants

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DESCRIPTION (provided by applicant): Infection following joint arthroplasty is a devastating complication with immense financial and psychological costs. Effective countermeasures to prevent osteolysis and infection include the use of body exhaust systems, laminar airflow and prophylactic antibiotics. Despite these measures, deep infection still occurs in 1-5 percent of joint replacements. The goal of this project is to engineer a "smart" prosthesis that addresses these problems. The scope of this highly integrated research requires collaboration across traditional academic boundaries. The proposed study will be spearheaded by investigators at two leading academic centers with strong emphasis on bioengineering, dental and orthopaedic research. The first objective will be to engineer a Ti surface that is osteogenic due to the presence of the adhesion peptide RGD. The broad spectrum antibiotic tigecyclin will be tethered to the metal using the adhesion peptide stem to yield a surface that is both osteogenic and anti-bacterial. We will measure the efficacy of the tigecyclin against a bacterial infection and determine the osteogenic potential of the tethered RGD peptide. In Specific Aim 2, a sol-gel film will be generated on the modified Ti surface that will release antibiotics and BMP-2. The osteogenic response and the release of the antibiotic linezolid from the sol-gel will be determined. In Specific Aim 3, we will engineer a prosthesis using these modified surfaces for in vivo testing in a dog hip infected with S. aureus. Immunogenicity, infection eradication, and bone formation/osseointegration will be evaluated. Following twelve weeks of recovery, femora will be recovered and analyzed using physical, optical, and histological techniques. Outcomes from this study will provide information for engineering of orthopaedic and dental implants that can be tested at the clinical level.