Rapid Integration of Articular Cartilage Implants Using Photochemical Bonding

描述（由申请人提供）：骨关节炎（OA）的特征是关节软骨、软骨下骨和其他关节组织的进行性退行性变，导致生活质量的严重下降和大量的经济成本。关节软骨缺损与骨性关节炎的加速进展有关，并且非常普遍，据报道，在关节镜检查的疼痛膝关节中，其发生率超过60%。据估计，仅在美国，每年就有至少50万例软骨修复手术。由于缺乏外侧软骨整合是导致移植物并发症和失败的关键因素，人们探索了缝合、粘接剂和光热组织焊接等方法来增强移植物的整合。我们的初步研究表明，光激活光化学软骨结合作为快速产生持久软骨到软骨结合的潜在策略的可行性。本研究的目标是通过一系列体内评估来扩展这一有希望的初步工作，以开发临床相关的光化学键合方案来治疗关节软骨缺陷。我们的具体目标是：1)台式阶段：优化光敏剂、表面处理和曝光条件，实现关节软骨的快速光化学结合；2)体外阶段：在体外软骨缺损修复模型中测定光化学键耐久性以及处理对细胞代谢和细胞外基质沉积的影响；3)体内阶段：测定光化学结合对兔同种异体骨软骨移植模型体内软骨整合的影响。这项工作的意义在于有可能改善越来越多的软骨修复手术的结果，并有可能应用于自然和工程组织移植。这项工作的创新之处在于开发了一种临床可行的光化学结合方法，适用于治疗全层软骨缺损并实现持久的外侧整合。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is characterized by progressive degeneration of articular cartilage, subchondral bone, and other joint tissues, resulting in a major reduction in quality of life and substantial economic costs. Articular cartilage defects are associated with accelerated OA progression and are surprisingly common, with a reported incidence of over 60% in arthroscopically examined painful knees. At least 500,000 cartilage repair procedures are estimated to be performed annually in the United States alone. As lack of lateral cartilage integration is a crucial factor leading to graft complications and failure, approaches including suturing, adhesives, and photothermal tissue welding have been explored to enhance graft integration. Our preliminary studies demonstrate the feasibility of light-activate photochemical cartilage bonding as a potential strategy for rapidly producing durable cartilage-to-cartilage bonding. The goal of this study is to extend this promising preliminary work to develop clinically relevant photochemical bonding protocols for treating articular cartilage defects through a series of evaluations culminating in an in vivo evaluation. Our specific aims are: 1) Benchtop phase: Optimize photosensitizer, surface treatment and exposure conditions to achieve rapid photochemical bonding of articular cartilage; 2) In vitro phase: Determine photochemical bond durability and effects of treatment on cell metabolism and extracellular matrix deposition in an in vitro cartilage defect repair model; 3) In vivo phase: Determine the effects of photochemical bonding on cartilage integration in vivo in a rabbit osteochondral allograft model. The significance of this work is in the potential to improve outcomes in the growing number of cartilage repair procedures, with potential application to both natural and engineered tissue grafts. The innovation of this work is in the development of a clinically feasibl photochemical bonding approach suitable for treating full thickness cartilage defects and achieving durable lateral integration.