Smart Substrates for a New Generation of Implants

描述（由申请人提供）：关节置换术后感染是一种毁灭性的并发症，具有巨大的经济和心理成本。预防骨溶解和感染的有效对策包括使用身体排气系统、层流和预防性抗生素。尽管采取了这些措施，深度感染仍然发生在1- 5%的关节置换术中。这个项目的目标是设计一个“智能”假肢来解决这些问题。这种高度整合的研究范围需要跨越传统学术界限的合作。这项提议的研究将由两个主要学术中心的研究人员带头，重点是生物工程、牙科和骨科研究。第一个目标是设计一种钛表面，由于粘连肽RGD的存在而具有成骨性。广谱抗生素替加环素将通过黏附肽茎附着在金属上，产生既成骨又抗菌的表面。我们将测量替加环素对抗细菌感染的功效，并确定栓系RGD肽的成骨潜能。在Specific Aim 2中，将在修饰的Ti表面生成溶胶-凝胶膜，该膜将释放抗生素和BMP-2。将测定该溶胶-凝胶的成骨反应和抗生素利奈唑胺的释放。在特定目标3中，我们将使用这些修饰的表面设计假体，用于感染金黄色葡萄球菌的狗髋关节的体内测试。免疫原性、感染根除和骨形成/骨整合将被评估。恢复12周后，股骨将恢复并使用物理、光学和组织学技术进行分析。本研究的结果将为骨科和牙科种植体的工程设计提供信息，可以在临床水平上进行测试。

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.