Integrated Cartilage Repair

综合软骨修复

• 批准号: 10221602
• 负责人: HELEN H LU
• 金额: $ 35.93万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-13 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221602
• 关键词: Address; Allogenic; American; Anabolism; Animal Model; Autologous; Biochemical; Biological; Biological Assay; Bone Transplantation; Cartilage; Cells; Ceramics; Chemistry; Chemotactic Factors; Chondrocytes; Clinical; Clinical Treatment; Country; Defect; Degenerative polyarthritis; Deposition; Development; Devices; Dose; Exhibits; Fiber; Fibrocartilages; Generations; Goals; Growth; Homing; Hydrogels; Hydroxyapatites; Immunohistochemistry; In Vitro; Insulin-Like Growth Factor I; Intervention; Kinetics; Lead; Left; Lesion; Mediating; Methods; Minerals; Modeling; Musculoskeletal; Nanotechnology; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Pain; Patients; Phenotype; Polymers; Production; Quality of life; Replacement Arthroplasty; Reporting; Research; Secure; Soft Tissue Injuries; Spatial Distribution; Stem Cell Factor; Structure; System; Systems Integration; Testing; Time; Tissue Adhesives; Tissue Engineering; Tissues; United States; Work; arthropathies; articular cartilage; base; bone; calcium phosphate; cartilage degradation; cartilage repair; cartilage transplantation; cell motility; clinically relevant; clinically significant; density; design; disability; experience; functional outcomes; healing; improved; in vivo; innovation; joint destruction; joint function; mechanical properties; migration; mineralization; nanofiber; nanoparticle; novel; osteochondral tissue; poly(lactide); prevent; repaired; response; restoration; sample fixation; soft tissue; subchondral bone; treatment strategy; tricalcium phosphate

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.

项目摘要 骨关节炎或软骨退化是最普遍的关节疾病之一，并且仍然是最常见的关节疾病。 这是这个国家工作残疾的常见原因目前的骨关节炎治疗方案往往失败， 软骨移植物和宿主组织之间缺乏整合，包括周围的软骨 和下面的骨头因此，对于软骨修复的综合解决方案存在未满足的临床需求。 该提案的目的是确定一个综合性的杯子系统在促进 移植物-软骨和移植物-骨整合。据推测，天然软骨整合将促进 控制软骨细胞向移植物-软骨连接处的迁移， 优化磷酸钙（CaP）纳米颗粒的生物活性、浓度和空间分布。为了验证这一 假设，将在体外（目标1和2）和体内（目标3）对髋臼杯系统进行评价， 基于水凝胶的软骨移植物，其表现出关节软骨范围内的机械性能。一个 骨软骨移植模型将用于测试移植物-软骨和移植物-骨的体外整合， 临床相关的兔骨关节炎模型将用于测试体内宿主组织整合。除了 通过免疫组织化学和生物化学测定评价细胞和组织表型， 诸如整合强度和跨组织边界的定量成分映射的结果将 也可用于测定体外和体内的功效。 除了针对临床上重要的问题，所提出的方法代表了一种新的范例， 软骨修复该集成系统是新颖的，因为其：1）独特的基于纳米纤维的杯设计， 2)促进同时移植物-软骨和移植物-骨整合的能力，和3）与各种 软骨移植这种创新的综合软骨修复方法将使软骨的恢复 完整性和长期功能。此外，这将有助于防止进一步的关节退化，从而减少 需要积极的和通常次优的干预措施（例如全关节置换和相关翻修 手术）。成功完成计划的研究将导致开发新一代的 用于治疗软组织损伤的基于纳米技术的固定装置。