Bionanomatrix coating to enhance antibacterial effects while reducing inflammation of knee joint implants

骨关节炎（OA）是一种退行性关节疾病，在美国影响超过3200万人， 引起使人衰弱的关节破坏和慢性关节疼痛、僵硬和身体损伤。恢复和 提高患者的生活质量，全膝关节置换术（TKA）是最常见的手术干预 对OA进行手术，用人工股骨和胫骨植入物置换受损关节。尽管继续 尽管TKA手术和植入物的进步，许多术后并发症仍然出现。不过 预计到2030年，TKA和后续翻修的需求将呈指数级增长至348万例患者 每年的医疗保健和患者成本将超过11亿美元。 虽然TKA对患者有有益的影响，但TKA最严重的并发症是感染、炎症， 和关节纤维化。感染的治疗是存在的，但这些通常是复杂和困难的;据我们所知， 除了重复手术或物理治疗外，没有可用的关节纤维化干预措施。此外，委员会认为， 临床研究对炎症的术后治疗没有给予足够的重视。因此，虽然 对于每种并发症可能存在单独的治疗，因此临床上需要多靶向的治疗。 方法来防止这些并发症的发展。 在第一阶段SBIR中，我们建议开发和评估一种多功能的一氧化氮（NO）和抗生素- 在钴铬（CoCr）膝关节植入物上释放BionanomatrixTM涂层的负载脂质体（ABLipo）。在 在体外，将优化植入物涂层，并表征其释放动力学、涂层均匀性/稳定性， 预防或减轻感染/生物膜形成、炎症和纤维化组织形成的能力。在体内，我们 将在兔TKA感染模型中评价涂层植入物的有效性。 BionanomatrixTM和ABLipo涂层平台的开发将针对TKA的严重并发症， 上面描述如果成功，这种方法和发现将很容易转化为其他骨科植入物 除了膝盖植入物。在成功完成第一阶段SBIR建议后，我们计划进一步开展这项研究 II期SBIR研究，包括大规模动物研究、微生物学机制评估，以及 ASTM/ISO标准化生物相容性研究，以备将来FDA申请。

Osteoarthritis (OA) is a degenerative joint disease that affects over 32 million individuals in the United States, causing debilitating joint destruction and chronic joint pain, stiffness, and physical impairment. To restore and improve the patient’s quality of life, total knee arthroplasty (TKA) is the most common surgical intervention performed for OA to replace the compromised joint with artificial femoral and tibial implants. Despite continued advancements in TKA procedures and implants, many post-operative complications still arise. Nonetheless, the demand for TKA and subsequent revisions is projected to grow exponentially to 3.48 million patients by 2030 with annual healthcare and patient costs to exceed $1.1 billion. While TKA has beneficial impacts on patients, the most critical complications of TKA are infection, inflammation, and arthrofibrosis. Treatments for infection exists, but these are usually involved and difficult; to our knowledge, there are no available interventions for arthrofibrosis beyond repeat surgery or physiotherapy. Furthermore, clinical studies have not paid sufficient attention to postoperative treatments of inflammation. Thus, while individual therapies may exist for each complication, there is a significant clinical need for a multi-targeted approach to prevent the development of these complications. In this Phase I SBIR, we propose to develop and evaluate a multifunctional, nitric oxide (NO) and antibiotic- loaded liposomes (ABLipo) releasing BionanomatrixTM coating on cobalt-chromium (CoCr) knee implants. In vitro, the implant coating will be optimized and characterized for release kinetics, coating uniformity/stability, and ability to prevent or mitigate infection/biofilm formation, inflammation, and fibrotic tissue formation. In vivo, we will evaluate the efficacy of the coated implants in a rabbit TKA infection model. Development of the BionanomatrixTM and ABLipo coating platform will target the critical complications of TKA as described above. If successful, this approach and findings will be readily translated to other orthopedic implants beyond knee implants. After successful completion of this Phase I SBIR proposal, we plan to further this research to a Phase II SBIR study with a larger-scale animal study, microbiological mechanism assessments, and ASTM/ISO standardized biocompatibility studies for future FDA applications.