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，深部感染仍然发生在1%-5%的关节置换手术中。这个项目的目标是设计一种“智能”假体来解决这些问题。这项高度整合的研究的范围需要跨越传统学术边界的合作。这项拟议的研究将由两个领先学术中心的研究人员带头进行，重点是生物工程、牙科和整形外科研究。第一个目标是设计一种钛表面，由于粘附肽RGD的存在，它是成骨的。广谱抗生素替吉环素将使用粘附肽将其连接到金属表面，以产生既成骨又抗菌的表面。我们将测量替格环素对细菌感染的疗效，并确定拴系的RGD多肽的成骨潜力。在特定目标2中，将在修饰的钛表面生成一层溶胶凝胶膜，该膜将释放抗生素和BMP-2。将测定成骨反应和抗生素利奈唑胺从溶胶-凝胶中的释放。在具体目标3中，我们将设计一种假体，使用这些改良的表面在感染金黄色葡萄球菌的狗臀部进行活体测试。将对免疫原性、感染根除和骨形成/骨整合进行评估。经过12周的恢复，股骨将被恢复，并使用物理、光学和组织学技术进行分析。这项研究的结果将为骨科和牙科植入物的工程提供信息，这些植入物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.