Integrated Cartilage Repair

综合软骨修复

• 批准号: 10466801
• 负责人: HELEN H LU
• 金额: $ 35.68万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10466801
• 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; 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; translational barrier; 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 骨关节炎或软骨变性是最普遍的关节疾病之一，仍然是最普遍的 这个国家与工作有关的残疾的常见原因。当前的骨关节炎治疗方案常常失败 软骨移植物和宿主组织之间缺乏整合，包括周围的软骨 和基础骨头。因此，对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综合纳米纤维杯系统促进的功效 移植物 - 肉食和移植骨整合。假设本地软骨整合将由 控制软骨细胞迁移到移植物 - - 卡托尔交界处，整骨将通过 优化磷酸钙（CAP）纳米粒子生物活性，浓度和空间分布。测试这个 假设，将在体外评估纳米纤维杯系统（目标1和2）和体内（AIM 3） 基于水凝胶的软骨移植物在关节软骨范围内具有机械性能。一个 骨软骨外植体模型将用于在体外测试移植物和移植骨整合，而A 临床相关的兔骨关节炎模型将用于在体内测试宿主组织的整合。此外 通过免疫组织化学和生化测定评估细胞和组织表型，其他功能 诸如整合强度和跨组织边界的定量组成映射等结果将 也可用于确定体外和体内功效。 除了针对临床意义的问题外，提出的方法还代表了新的范式 软骨维修。纳米纤维集成系统是新颖的，因为它具有：1）独特的基于纳米纤维的杯子设计， 2）能够促进同时的移植物和移植骨整合的能力，3）与多种兼容性 软骨移植物。这种综合软骨维修的创新方法将使软骨的恢复 完整性和长期功能。此外，它将有助于防止进一步的联合变性，从而减少 需要积极进取的，通常是次优的干预措施（例如，总关节置换和相关的修订 手术）。成功完成计划研究将导致新一代的发展 基于纳米技术的固定装置，用于治疗软组织损伤。

项目成果

Polymeric mesh and insulin-like growth factor 1 delivery enhance cell homing and graft-cartilage integration.

• DOI: 10.1111/nyas.14054
• 发表时间: 2019-04
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Boushell MK;Mosher CZ;Suri GK;Doty SB;Strauss EJ;Hunziker EB;Lu HH
• 通讯作者: Lu HH

Green electrospinning for biomaterials and biofabrication.

• DOI: 10.1088/1758-5090/ac0964
• 发表时间: 2021-06-28
• 期刊: Biofabrication
• 影响因子: 9
• 作者: Mosher CZ;Brudnicki PAP;Gong Z;Childs HR;Lee SW;Antrobus RM;Fang EC;Schiros TN;Lu HH
• 通讯作者: Lu HH