Integrated Cartilage Repair

项目总结 骨性关节炎，或软骨退行性变，是最常见的关节疾病之一，也是最常见的 这是这个国家与工作相关的残疾的共同原因。目前的骨关节炎治疗方案经常失败，因为 软骨移植物与宿主组织，包括周围软骨之间缺乏整合 和下面的骨头。因此，临床上对软骨修复的综合解决方案的需求还没有得到满足。 该提案的目的是确定一体化纳米纤维杯系统在促进 移植物-软骨和移植物-骨结合。据推测，天然软骨的整合将通过 控制软骨细胞向移植物-软骨交界处的迁移，并促进骨整合 优化磷酸钙纳米颗粒的生物活性、浓度和空间分布。为了测试这一点 假设，纳米纤维杯系统将在体外(目标1和2)和体内(目标3)进行评估， 以水凝胶为基础的软骨移植，在关节软骨范围内表现出力学性能。一个 骨软骨移植模型将用于体外测试移植物-软骨和移植物-骨的结合，而 临床相关的兔骨关节炎模型将用于体内检测宿主组织的整合。除了……之外 通过免疫组织化学和生化分析评估细胞和组织表型，其他功能 结果，如整合强度和跨组织边界的定量成分图谱将 也可用于测定体外和体内的药效。 除了针对临床上有重要意义的问题外，建议的方法还代表了 软骨修复。纳米纤维集成系统是新颖的，因为它：1)独特的基于纳米纤维的杯状设计， 2)同时促进移植软骨和移植骨整合的能力；3)与各种 软骨移植。这种综合软骨修复的创新方法将使软骨修复成为可能 诚信和长远的功能。此外，这将有助于防止进一步的关节退变，从而减少 需要积极的、往往不太理想的干预措施(例如，完全关节置换和相关的翻修 手术)。成功完成计划中的研究将导致开发新一代 用于治疗软组织损伤的基于纳米技术的固定装置。

PROJECT SUMMARY Osteoarthritis, or degeneration of cartilage, is one of the most prevalent joint diseases and remains the most common cause of work-related disabilities in this country. Current osteoarthritis treatment options often fail due to lack of integration between the cartilage graft and the host tissues, including both the surrounding cartilage and underlying bone. Therefore, there exists an unmet clinical need for integrative solutions for cartilage repair. The objective of the proposal is to determine the efficacy of an integrative nanofiber cup system in promoting graft-cartilage and graft-bone integration. It is hypothesized that native cartilage integration will be facilitated by controlling chondrocyte migration to the graft-cartilage junction, and osteointegration will be enhanced by optimizing calcium phosphate (CaP) nanoparticle bioactivity, concentration and spatial distribution. To test this hypothesis, the nanofiber cup system will be evaluated both in vitro (Aims 1 and 2) and in vivo (Aim 3) with a hydrogel-based cartilage graft that exhibits mechanical properties within the range of articular cartilage. An osteochondral explant model will be used to test both graft-cartilage and graft-bone integration in vitro, while a clinically relevant rabbit osteoarthritis model will be used to test host tissue integration in vivo. In addition to evaluating cell and tissue phenotypes via immunohistochemistry and biochemical assays, other functional outcomes such as integration strength and quantitative compositional mapping across tissue boundaries will also be used to determine efficacy in vitro and in vivo. In addition to targeting a clinically significant problem, the proposed approach represents a new paradigm in cartilage repair. The nanofiber integration system is novel because of its: 1) unique nanofiber-based cup design, 2) ability to promote simultaneous graft-cartilage and graft-bone integration, and 3) compatibility with a variety of cartilage grafts. This innovative approach for integrated cartilage repair will enable the restoration of cartilage integrity and long-term function. Moreover, it will help to prevent further joint degeneration and thereby reduce the need for aggressive and often suboptimal interventions (e.g. total joint replacements and related revision surgeries). Successful completion of the planned studies will lead to the development of a new generation of nanotechnology-based fixation devices for the treatment of soft tissue injuries.