Knee Joint Resurfacing with Anatomic Tissue Engineered Osteochondral Implants

使用解剖组织工程骨软骨植入物进行膝关节表面置换

• 批准号: 10454898
• 负责人: Robert L Mauck
• 金额: --
• 依托单位: PHILADELPHIA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10454898
• 关键词: 3D Print; Activities of Daily Living; Address; Affect; Anatomy; Animal Model; Animals; Arthritis; Articular Range of Motion; Autologous; Benchmarking; Biochemical; Biological; Biological Assay; Biological Models; Biological Process; Biology; Biomedical Engineering; Cartilage; Cartilage injury; Clinical; Clinical Trials; Complex; Coupled; Custom; Data; Degenerative polyarthritis; Deposition; Engineering; Evaluation; Extracellular Matrix; Fluoroscopy; Funding; Generations; Geometry; Goals; Growth; Hip Osteoarthritis; Histologic; Human; Hyaluronic Acid; Hydrogels; Image; Implant; In Vitro; Inflammation; Inflammatory; Injury; Intervention; Joints; Knee; Knee Osteoarthritis; Knee joint; Lead; Life Expectancy; Mechanics; Medial; Meniscus structure of joint; Mesenchymal Differentiation; Mesenchymal Stem Cells; Metals; Methods; Miniature Swine; Modeling; Molds; Motion; Operative Surgical Procedures; Outcome; Outcome Measure; Patients; Population; Pre-Clinical Model; Property; Prosthesis; Quality of life; Reaction; Replacement Arthroplasty; Sampling; Services; Societies; Stress; Surface; Surgical Management; Symptoms; System; Techniques; Technology; Testing; Time; Tissue Engineering; Tissues; Translating; Traumatic Arthropathy; Veterans; Weight-Bearing state; Work; aged; articular cartilage; base; bone; cartilage repair; clinical practice; clinical translation; clinically relevant; comorbidity; contrast enhanced; efficacy testing; experimental study; functional outcomes; healing; histological image; implantation; in vivo; joint biomechanics; joint function; joint injury; joint loading; loss of function; mechanical properties; microCT; military veteran; novel; osteochondral tissue; pre-clinical; preservation; sample fixation; scaffold; stem cells; success; supportive environment

Abstract Articular cartilage lines the boney surfaces of joints and efficiently transmits the high stresses that originate with activities of daily living. However, damage to this tissue is extremely prevalent, with ~9% of the U.S. population aged 30 and older having osteoarthritis (OA) of the hip or knee. This adversely impacts the many Veterans with this condition, limiting their ability to carry out many activities of daily living and lowering their overall quality of life. Unfortunately, there are very few viable treatment options for patients with damaged articular cartilage, and most culminate in joint replacement with metal and plastic prostheses, which are prone to wear and ultimately require revision surgery. To address this clinical need, we developed novel hydrogels that promote the chondrogenic differentiation of mesenchymal stem cells (MSCs) and provide a supportive environment for extracellular matrix deposition and functional maturation of a cartilage-like tissue, both in vitro and in our Yucatan minipig large animal model of cartilage repair. Moreover, we recently demonstrated that living, engineered cartilage constructs can be formed into anatomic structures that mimic the complex geometries of native joint surfaces. We have also developed technology that enables the permanent boney fixation and in vivo integration of the living implant with existing bone. In this proposal, we capitalize on this progress to address the `holy grail' of biologic joint resurfacing: replacement of the majority of a load-bearing articular cartilage surface. Our experiment will use the femoral condyle of the Yucatan minipig as a model, and success will be assessed via sophisticated and clinically relevant outcome measures. Once validated in this pre-clinical setting, this technology may be directly translated into human clinical trials, and extended to other joints in the body. Ultimately, this work may one day eliminate the need for joint replacement with metal and plastic and alleviate the serious implications of OA in the Veteran population, as well as society as a whole.

抽象的 关节软骨线的关节表面并有效地传输了起源的高应力 与日常生活的活动。但是，对该组织的损害极为普遍，大约9％的美国 髋或膝盖的骨关节炎（OA）的30岁及以上的人口。这对许多人产生了不利影响 有这种情况的退伍军人，限制了他们进行许多日常生活的能力，并降低他们 整体生活质量。不幸的是，损坏的患者几乎没有可行的治疗选择 关节软骨，最终用金属和塑料假体替代关节，易于 佩戴并最终需要修改手术。为了满足这种临床需求，我们开发了新型水凝胶 促进间充质干细胞（MSC）的软骨分化并提供了支持 细胞外基质沉积和软骨样组织功能成熟的环境，均在体外 在我们的Yucatan Minipig大型软骨修复模型中。此外，我们最近证明了 生活，工程的软骨构建体可以形成模仿复合物的解剖结构 天然关节表面的几何形状。我们还开发了实现永久性的技术 固定和体内植入物与现有骨骼的体内整合。在此提案中，我们利用了这一点 解决生物学关节重新铺面的“圣杯”的进展：替代大多数负载 关节软骨表面。我们的实验将将Yucatan Minipig的股骨con作为模型，并且 成功将通过复杂和临床相关的结果指标评估。一旦在此验证 临床前的环境，该技术可以直接转化为人类临床试验，并扩展到其他 体内的关节。最终，这项工作可能有一天消除了用金属替换的连接需求 塑料并减轻OA对退伍军人人口以及整个社会的严重影响。