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.

摘要