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

生物纳米基质涂层可增强抗菌效果，同时减少膝关节植入物的炎症

• 批准号: 10822220
• 负责人: Jennifer Sherwood
• 金额: $ 29.26万
• 依托单位: ENDOMIMETICS, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10822220
• 关键词: 3D Print; Address; Affect; Amputation; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibiotics; Arthralgia; Articular Range of Motion; Artificial Implants; Attention; Biological; Chromium; Chronic; Cicatrix; Clinical; Clinical Research; Cobalt; Complication; Custom; Cytolysis; Day Surgery; Debridement; Degenerative polyarthritis; Development; Dose; Encapsulated; Evaluation; Femur; Fibrosis; Foreign Bodies; Future; Goals; Health Care Costs; Healthcare; Impairment; Implant; In Vitro; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Intervention; Joints; Kinetics; Knee; Knee Prosthesis; Knee joint; Legal patent; Limb structure; Liposomes; Methods; Microbial Biofilms; Modeling; Movement; Nitric Oxide; Operative Surgical Procedures; Oral; Organic solvent product; Orthopedics; Oryctolagus cuniculus; Pain; Patients; Peptides; Periprosthetic joint infection; Pharmaceutical Preparations; Phase; Physical therapy; Postoperative Complications; Postoperative Period; Prevalence; Prevention; Prevention strategy; Procedures; Property; Quality of life; Recovery; Regimen; Repeat Surgery; Replacement Arthroplasty; Reporting; Research; Risk; Rotation; Second Look Surgery; Small Business Innovation Research Grant; Standardization; Surgical complication; Time; Tissues; Translating; Ultrasonics; United States; biomaterial compatibility; chronic pain; comorbidity; cost; design; efficacy evaluation; efficacy validation; hospital readmission; implant coating; implantation; improved; in vivo; innovation; joint destruction; joint infection; knee replacement arthroplasty; manufacture; mortality; novel; pathogen; phase 1 study; prevent; response

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.

骨关节炎（OA）是一种退化性关节疾病，影响了美国超过3200万人， 引起衰弱的关节破坏和慢性关节疼痛，僵硬和身体障碍。恢复和 提高患者的生活质量，总膝关节置换术（TKA）是最常见的手术干预 为OA进行的，用人造股骨和胫骨即可代替受损的关节。尽管继续 TKA程序和直接的进步，许多术后并发症仍会出现。尽管如此， 预计到2030 年度医疗保健和患者费用超过11亿美元。 尽管TKA对患者产生有益的影响，但TKA最关键的并发症是感染，炎症， 和关节纤维化。存在感染的治疗方法，但通常涉及且困难；据我们所知， 除了重复手术或物理疗法外，没有可用的关节纤维化干预措施。此外， 临床研究尚未充分注意术后炎症治疗。那，而 每种并发症可能都存在单个疗法，对多目标有很大的临床需求 防止这些并发症发展的方法。 在此I阶段，我们建议开发和评估多功能，一氧化氮（NO）和抗生素 - 在钴 - 铬（COCR）膝盖上释放了bionanomatrixtm涂层的脂质体（Ablipo）。在 体外，植入物涂料将被优化和特征，以释放动力学，涂层均匀性/稳定性以及 预防或减轻感染/生物膜形成，感染和纤维化组织形成的能力。在体内，我们 将评估兔子TKA感染模型中涂层牙齿的效率。 Bionanomatrixtm和Ablipo涂料平台的开发将以TKA的关键并发症为目标 上面描述。如果成功的话，这种方法和发现将很容易转化为其他骨科植入 超越膝盖。成功完成了这一阶段的SBIR提案后，我们计划进一步进行这项研究 进行II阶段SBIR研究，并进行大规模动物研究，微生物机制评估和 ASTM/ISO标准化生物相容性研究，用于未来的FDA应用。