Performance Evaluation of a non-Degradable Synthetic Device for Chondral and Osteochondral Defects of the Knee

关节损伤会导致关节软骨和下层骨的疼痛缺陷，从而对健康造成不良影响 整个关节的功能和生物健康。目前用于软骨(软骨)和软骨的解决方案- 骨(骨软骨)缺陷是不可靠的，在技术上具有挑战性，通常需要多次手术。 特殊外科医院(HSS)的外科医生、工程师和生物学家团队致力于10年的研究 这个问题的解决方案的设计和功能评估，导致了第一个剥离的形成 HSS是一家拥有156年历史的公司。AGelity-OCI(骨软骨植入)，是一种非细胞、非 可降解合成装置，由两层组成：聚乙烯醇水凝胶，PVA，集成到 多孔钛基座。PVA层采用坚固的核心设计，可承受生理负荷，并拥有专利 受保护的同心多孔海绵，原位水化，产生舒适的按压-贴合宿主关节 软骨，导致侧向整合。使用体外、硅胶和活体模型，我们已经证明 AGelity-OCI与骨和关节软骨结合，不会导致关节滑膜炎、炎症或损伤 对于关节的相对表面，PVA和多孔钛之间的界面(使用 第一阶段SBIR资金)保持机械完整性，该装置分配的载荷类似于天然组织。 这项研究的目的是全面表征机械，结构，化学，形态，生物， 根据监管指南，AGelity-OCI的功能特征。我们最重要的假设是 AGelity-OCI是一种安全有效的治疗局灶性软骨和骨软骨缺损的装置。这 假设将通过两个具体目标进行检验。具体目标1：表征化学、形态、 以及我们制造的灭菌后装置及其部件的材料性能。我们的假设是 该设备将符合联邦安全指南。具体目标2：确定生物和生物的特征 AGelity-OCI的功能性活体行为。我们的假设是，AGelity-OCI将不会比新鲜冷冻的产品差 同种异体骨软骨移植。我们将该设备商业化的努力正处于成熟的转换风险降低阶段： (I)2018年2月与食品和药物管理局举行的集成开发前会议已经完成；会议记录详细说明 在目前的提案中，(Ii)知识产权受五项专利保护，(Iii)AGelity-OCI目前 由FDA注册和ISO认证的制造工厂制造、包装和灭菌；以及(Iv) 核心调查团队涵盖工程、外科、制造、临床前测试、监管和 商业战略。我们的基于设备的方法代表着当前模式的重大转变 骨软骨缺损的治疗避免了基于细胞的方法和 贪污的技术和后勤挑战。这项研究的成功完成将使我们能够 为AGelity-OCI进行首个面对面的研究，为 软骨和骨软骨缺损的处理。

Injury to joints can lead to painful defects in articular cartilage and the underlying bone, which adversely affect the function and biological health of the entire joint. Current solutions for cartilage (chondral) and cartilage-and- bone (osteochondral) defects, are unreliable, are technically challenging, and often require multiple procedures. A surgeon-engineer-biologist team at Hospital for Special Surgery (HSS) dedicated >10 years of research to the design and functional evaluation of a solution to this problem which led to the formation of the first spin-out company from HSS in its 156-year history. AGelity-OCI (OsteoChondral Implant), is a non-cell based, non- degradable synthetic device, consisting of two layers: a poly(vinyl alcohol) hydrogel, PVA, integrated into a porous Titanium base. The PVA layer is designed with a solid core to withstand physiological loads and a patent protected concentric porous sponge that hydrates in situ to produce a snug press-fit against the host articular cartilage, leading to lateral integration. Using in vitro, in silico, and in vivo models we have demonstrated that AGelity-OCI integrates with bone and articular cartilage without causing joint synovitis, inflammation, or damage to the opposing surfaces of the joint, the interface between PVA and porous titanium (which was optimized using Phase I SBIR funds) maintains mechanical integrity, and the device distributes loads similar to the native tissue. The objective of this study is to fully characterize the mechanical, structural, chemical, morphological, biological, and functional characteristics of AGelity-OCI as per regulatory guidelines. Our over-arching hypothesis is that AGelity-OCI is a safe and effective device for the treatment of focal chondral and osteochondral defects. This hypothesis will be tested using two Specific Aims. Specific Aim 1: To characterize the chemical, morphological, and materials performance of our as-manufactured post-sterilized device and its components. Our hypothesis is that the device will meet federal guidelines for safety. Specific Aim 2: To characterize the biological and functional in vivo behavior of AGelity-OCI. Our hypothesis is that AGelity-OCI will be non-inferior to fresh frozen osteochondral allografts. Our efforts to commercialize this device are at a mature translational de-risked stage: (i) a Pre-IDE meeting with the FDA in February 2018 was completed; the minutes from which frame the details of the current proposal (ii) intellectual property is protected by five patents, (iii) AGelity-OCI is currently manufactured, packaged and sterilized by an FDA registered and ISO certified manufacturing facility, and (iv) the core investigative team spans engineering, surgery, manufacture, pre-clinical testing, regulatory and business strategy. Our device-based approach represents a significant shift in the current paradigm for the treatment of osteochondral defects by avoiding the highly variable results from cell-based approaches and the technical and logistical challenges of graft usage. Successful completion of this study will enable our trajectory to conduct first-in-man studies for AGelity-OCI, resulting in a cost-effective functional solution for the management of chondral and osteochondral defects.