Smart Hip Implants with Modified Biological Surface

描述(由申请人提供)：本提案描述了一项为期五年的临床医生-科学家发展培训计划。这项合作研究的目的是为PI提供一个刺激的培训环境，PI是一名训练有素的整形外科医生，专门从事关节重建。该提案整合了来自不同学科(生物化学、生物工程、材料科学、分子生物学、细胞生物学和整形外科)的国际公认的研究人员，利用他们的专业知识培训PI并解决紧迫的临床问题。尽管采取了广泛而有效的措施，假体周围感染仍然影响着1-5%的关节置换手术。随着美国每年进行超过60万次关节置换，预计到2030年，这一数字将超过100万，假体周围感染给医疗保健和患者带来了巨大的经济和心理负担。这项研究计划的目标是开发一种“智能”假体来解决这一重要问题。粘附肽(RGD)和抗生素(Linezolid)将直接连接到钛(Ti)种植体的表面，以促进骨整合，并根据需要控制感染。此外，钛将被一层薄的、可溶的溶胶-凝胶膜覆盖，该薄膜将释放抗生素，以根除细菌感染。这种“智能”植入物的有效性将在狗的模型中进行测试，以评估其杀菌和成骨潜力。植入物表面的早期释放和耐用的捆绑抗生素相结合，为髋关节周围提供了一个有效的抗菌环境，可以将早期和晚期感染的发生率降至最低。这项技术的发展将满足骨科手术治疗关节成形术最可怕的两种并发症--假体周围感染和骨溶解--的真正需求。因此，患者的痛苦、痛苦和发病率将降至最低。

DESCRIPTION (provided by applicant): This proposal describes a five-year training program for the development of a clinician-scientist. This collaborative research effort is intended to provide a stimulating training environment for the PI who is a fully trained orthopedic surgeon specializing in joint reconstruction. The proposal integrates internationally recognized investigators from various disciplines (Biochemistry, Bioengineering, Materials Science, Molecular Biology, Cell Biology, and Orthopedic Surgery) to use their expertise in training the PI and to address a pressing clinical problem. Despite extensive and effective measures, periprosthetic infection continues to affect 1-5 percent of joint replacements. With over 600,000 joint replacements being performed annually in the US and an expected rise in this number to exceed 1 million by the year 2030, periprosthetic infection poses a substantial economic and psychological burden to the healthcare and the patients. The objective of this research proposal is to develop a 'smart' prosthesis that addresses this important problem. Adhesion peptides (RGD) and antibiotic (Linezolid) will be linked directly to the surface of the titanium (Ti) implant to promote osseointegration and, on-demand, to control infection. In addition, the Ti will be covered with a thin, soluble sol-gel film that will release antibiotics to eradicate bacterial infections. The efficacy of the "smart" implant will be tested in a dog model to evaluate its bactericidal and osteogenic potential. The combination of early release and durable tethered antibiotic on the surface of the implant provides an effective antibacterial milieu around the hip that can minimize the incidence of early and late infections. The development of this technology will address a real need in orthopedic surgery in treating two of the most dreaded complications of arthroplasty, namely periprosthetic infection and osteolysis. As a result, patient pain, suffering and morbidity will be minimized.