Smart Hip Implants with Modified Biological Surface

描述（由申请人提供）：该提案描述了一个临床科学家发展的五年培训计划。这项合作研究旨在为PI提供一个刺激的培训环境，PI是一名训练有素的骨科医生，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）的国际知名研究人员，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%的关节置换术。美国每年进行的关节置换手术超过60万例，预计到2030年这一数字将超过100万例，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”假肢来解决这一重要问题。粘附肽（RGD）和抗生素（利奈唑胺）将直接连接到钛（Ti）种植体表面，以促进骨整合并按需控制感染。此外，Ti将被一层薄的可溶性溶胶-凝胶膜覆盖，该膜将释放抗生素以消除细菌感染。“智能”植入物的功效将在狗模型中进行测试，以评估其杀菌和成骨潜力。早期释放和植入物表面持久的系留抗生素的结合为髋关节周围提供了有效的抗菌环境，可以最大限度地减少早期和晚期感染的发生率。这项技术的发展将解决骨科手术治疗关节成形术中两个最可怕的并发症的实际需求，即假体周围感染和骨溶解。因此，病人的痛苦、折磨和发病率将被降到最低。

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.