Smart Substrates for a New Generation of Implants

关节置换术后感染是一种破坏性的并发症，具有巨大的经济和心理问题。 成本。防止骨溶解和感染的有效措施包括使用身体排气 系统、层流气流和预防性抗生素。尽管采取了这些措施，深度感染仍在发生。 在1-5%的关节置换中。该项目的目标是设计一种“智能”假肢， 解决了这些问题。这项高度集成的研究范围需要跨领域的协作 传统的学术界限。拟议的研究将由两家领先的调查机构带头进行 以生物工程、牙科和矫形外科研究为重点的学术中心。第一 目标是设计一种钛表面，由于粘附肽的存在，它是成骨的 RGD。广谱抗生素替吉环素将使用粘附肽与金属捆绑在一起 以产生既成骨又抗菌的表面我们将测量 替吉环素治疗细菌感染，并确定拴系的RGD多肽的成骨潜力。 在特定目标2中，将在改性的钛表面上生成一层溶胶凝胶膜，该膜将释放抗生素和 骨形态发生蛋白-2。成骨反应和抗生素利奈唑胺从溶胶-凝胶中的释放将是 下定决心。在特定的目标3中，我们将设计一种使用这些改良表面的体内假体 在感染了金黄色葡萄球菌的狗臀部进行测试。免疫原性、感染根除和骨骼 将对形成/骨整合进行评估。在12周的恢复之后，Femora将会是 使用物理、光学和组织学技术进行恢复和分析。这项研究的结果将 为可在临床进行测试的骨科和牙科植入物的工程提供信息 水平。

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.