Rapid Integration of Articular Cartilage Implants Using Photochemical Bonding

描述(申请人提供)：骨性关节炎(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化，导致生活质量的显著下降和大量的经济成本。关节软骨缺陷与加速的骨性关节炎进展有关，而且出人意料地常见，据报道，在关节镜检查的疼痛的膝关节中，发病率超过60%。据估计，仅在美国，每年就有至少50万例软骨修复手术。由于缺乏侧向软骨的整合是导致移植并发症和失败的关键因素，人们探索了包括缝合、粘合剂和光热组织焊接等方法来提高移植骨的整合。我们的初步研究表明，光激活光化学软骨结合作为一种潜在的策略来快速产生持久的软骨-软骨结合是可行的。这项研究的目的是通过一系列的评估来扩展这项有希望的前期工作，以开发临床上相关的光化学粘合方案来治疗关节软骨缺损，最终达到体内评估。我们的具体目标是：1)台面阶段：优化光敏剂、表面处理和曝光条件，以实现关节软骨的快速光化学结合；2)体外阶段：在兔同种异体骨软骨移植模型中，确定光化学结合的持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：在兔同种异体骨软骨移植模型中确定光化学结合对软骨整合的影响。这项工作的意义在于有可能改善越来越多的软骨修复程序的结果，潜在地应用于天然和工程组织移植。这项工作的创新之处在于开发了一种临床上可行的光化学粘合方法，适用于治疗全层软骨缺损并实现持久的侧向整合。

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.