Rapid Integration of Articular Cartilage Implants Using Photochemical Bonding

利用光化学粘合快速整合关节软骨植入物

• 批准号: 8512184
• 负责人: MARC Elliot LEVENSTON
• 金额: $ 16.71万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8512184
• 关键词: Acids; Adhesives; Allografting; Animals; Area; Bone Transplantation; Cartilage; Cell Death; Cell Survival; Cells; Charge; Chondroitin ABC Lyase; Cleaved cell; Clinical; Collagen; Defect; Degenerative polyarthritis; Deposition; Detection; Development; Digestion; Effectiveness; Evaluation; Exposure to; Extracellular Matrix; Failure; Generations; Goals; Histology; Image; Implant; In Vitro; Incidence; Injury; Interleukin-1; Investigation; Joints; Knee; Laboratory Animals; Laboratory Study; Lactate Dehydrogenase; Lasers; Lateral; Lead; Left; Life; Light; Lighting; Location; Measurement; Medial; Mediating; Metabolic; Metabolism; Methods; Modeling; Morphology; Natural regeneration; New Zealand; Optical Coherence Tomography; Oryctolagus cuniculus; Osteoarthrosis Deformans; Outcome; Pain; Performance; Phase; Photosensitizing Agents; Procedures; Process; Proteins; Protocols documentation; Quality of life; Reporting; Resistance; Resources; Series; Shear Strength; Site; Staining method; Stains; Structure; Surface; Surgical sutures; Techniques; Testing; Thick; Time; Tissue Engineering; Tissue Grafts; Tissues; Transplantation; Treatment Protocols; United States; Variant; Work; Workplace; aggrecan; aluminum phthalocyanine; articular cartilage; base; bone; cartilage repair; clinically relevant; density; economic cost; imaging modality; improved; in vivo; innovation; interfacial; irradiation; novel; novel strategies; osteochondral tissue; photoactivation; polysulfated glycosaminoglycan; public health relevance; repaired; response; success; tissue welding; tomography; treatment effect

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.

描述（由申请人提供）：骨关节炎（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，导致生活质量大幅降低和经济成本大幅增加。关节软骨缺损与加速的OA进展相关，并且令人惊讶地常见，在关节镜检查的疼痛膝关节中报告的发生率超过60%。据估计，仅在美国每年就进行至少50万例软骨修复手术。由于缺乏外侧软骨整合是导致移植物并发症和失败的关键因素，因此已经探索了包括粘合剂、粘合剂和光热组织焊接在内的方法来增强移植物整合。我们的初步研究表明，光激活的光化学软骨粘接作为一个潜在的战略，快速产生持久的软骨-软骨粘接的可行性。本研究的目的是扩展这一有前途的初步工作，开发临床相关的光化学键合协议，通过一系列的评估，最终在体内评价治疗关节软骨缺损。我们的具体目标是：1）实验室阶段：优化光敏剂、表面处理和暴露条件，实现关节软骨的快速光化学结合; 2）体外阶段：在体外软骨缺损修复模型中确定光化学结合耐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：在兔骨软骨同种异体移植模型中确定光化学结合对体内软骨整合的影响。这项工作的意义在于有可能改善越来越多的软骨修复手术的结果，并有可能应用于天然和工程组织移植物。这项工作的创新之处在于开发了一种临床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。