Smart Substrates for a New Generation of Implants

用于新一代植入物的智能基底

• 批准号: 7126471
• 负责人: IRVING M SHAPIRO
• 金额: $ 55.67万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-22 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7126471
• 关键词: Staphylococcus aureus; antibiotics; bioengineering /biomedical engineering; biomaterial development /preparation; biomaterial interface interaction; biotechnology; bone morphogenetic proteins; dogs; joint prosthesis; laboratory mouse; medical implant science; opportunistic infections; surface coating

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.

描述（由申请人提供）：联合置换术后感染是巨大的财务和心理成本的破坏性并发症。预防骨溶解和感染的有效对策包括使用人体排气系统，层流气流和预防性抗生素。尽管采取了这些措施，但仍有1-5％的关节替代品发生深层感染。该项目的目的是设计一个“智能”假体，以解决这些问题。这项高度综合研究的范围需要在传统的学术边界进行协作。拟议的研究将由两个领先的学术中心的研究人员率领，重点是生物工程，牙科和骨科研究。第一个目标是设计由于存在粘附肽RGD而具有成骨的Ti表面。宽光谱抗生素tigecyclin将使用粘附肽茎束缚在金属上，以产生既具有成骨和抗细菌的表面。我们将测量Tigecyclin对细菌感染的功效，并确定束缚的RGD肽的成骨潜力。在特定的目标2中，将在将释放抗生素和BMP-2的改良Ti表面上产生溶胶 - 凝胶膜。将确定成骨反应和抗生素线的释放，从溶胶 - 凝胶中确定。在特定的目标3中，我们将使用这些修饰的表面在感染金黄色葡萄球菌的狗髋关节中进行体内测试。将评估免疫原性，消除感染和骨形成/骨整合。恢复十二周后，将使用物理，光学和组织学技术对股骨进行回收和分析。这项研究的结果将为可以在临床水平进行测试的骨科和牙科植入物的工程提供信息。