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

基本信息

批准号：
8636401
负责人：
MARC Elliot LEVENSTON
金额：
$ 20.28万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8636401
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

项目摘要

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变性，从而大大降低了生活质量和实质性经济成本。关节软骨缺陷与加速的OA进展有关，令人惊讶的是，据报道，关节镜检查的疼痛膝盖的发生率超过60％。据估计，至少每年在美国进行500,000个软骨修复程序。由于缺乏侧向软骨的整合是导致移植并发症和失败的关键因素，因此已经探索了包括缝合，粘合剂和光热组织焊接在内的方法，以增强移植物的整合。我们的初步研究表明，光活化光化软骨键合的可行性是快速生产持久软骨至 - 核酸果粘结的潜在策略。这项研究的目的是扩展这项有希望的初步工作，以开发临床相关的光化学键合协议，以通过一系列评估最终在体内评估中处理关节软骨缺陷。我们的具体目的是：1）台式阶段：优化光敏剂，表面处理和暴露条件，以实现关节软骨的快速光化学键合； 2）体外阶段：确定在体外软骨缺陷修复模型中治疗对细胞代谢和细胞外基质沉积的影响的光化学键耐用性和影响； 3）体内阶段：确定光化学键对兔骨软骨同种异体移植模型体内软骨整合的影响。这项工作的重要性在于有可能改善软骨修复程序数量的预后，并可能应用于天然和工程组织移植物。这项工作的创新在于开发一种临床上的轻度光化学键合方法，适合治疗全厚度软骨缺陷并实现持久的侧面整合。