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: 10704534
• 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/10704534
• 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; Femur; 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; 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; Second Look Surgery; 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; bone; cartilage repair; clinical practice; clinical translation; clinically relevant; comorbidity; contrast enhanced; efficacy testing; experimental study; fabrication; functional outcomes; healing; implantation; in vivo; joint biomechanics; joint function; joint injury; joint loading; mechanical properties; microCT; military veteran; novel; osteochondral tissue; pre-clinical; preservation; sample fixation; scaffold; stem cells; success; supportive environment; transmission process

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 关节软骨排列在关节的骨表面上，并有效地传递产生的高应力 与日常生活活动。然而，这种组织的损伤极为普遍，美国约有 9% 的组织受到损伤。 30 岁及以上患有髋部或膝部骨关节炎 (OA) 的人群。这给很多人带来了负面影响 患有这种疾病的退伍军人限制了他们进行许多日常生活活动的能力并降低了他们的能力 整体生活质量。不幸的是，对于受损患者来说，可行的治疗选择很少 关节软骨，大多数最终导致使用金属和塑料假体进行关节置换，这很容易发生 佩戴并最终需要进行修复手术。为了满足这一临床需求，我们开发了新型水凝胶 促进间充质干细胞（MSC）的软骨形成并提供支持性 细胞外基质沉积和软骨样组织功能成熟的环境，均在体外 以及我们的尤卡坦小型猪软骨修复大型动物模型。此外，我们最近证明了 活的、工程化的软骨结构可以形成模仿复杂的解剖结构 原生关节表面的几何形状。我们还开发了能够实现永久骨化的技术 活体植入物与现有骨骼的固定和体内整合。在本提案中，我们利用了这一点 在解决生物关节表面重修的“圣杯”方面取得的进展：更换大部分承重关节 关节软骨表面。我们的实验将使用尤卡坦小型猪的股骨髁作为模型，并且 将通过复杂且临床相关的结果指标来评估成功与否。一旦在此验证 临床前环境下，该技术可直接转化为人体临床试验，并扩展到其他领域 身体的关节。最终，这项工作有一天可能会消除金属关节置换术的需要 塑料并减轻骨关节炎对退伍军人以及整个社会的严重影响。

项目成果

Fabrication of MSC-laden composites of hyaluronic acid hydrogels reinforced with MEW scaffolds for cartilage repair.

制造含有 MSC 的透明质酸水凝胶复合材料，并用 MEW 支架加固，用于软骨修复。

• 发表时间: 2021-12-01
• 影响因子: 9
• 作者: Galarraga, Jonathan H;Locke, Ryan C;Witherel, Claire E;Stoeckl, Brendan D;Castilho, Miguel;Mauck, Robert L;Malda, Jos;Levato, Riccardo;Burdick, Jason A
• 通讯作者: Burdick, Jason A

Gravity-based patterning of osteogenic factors to preserve bone structure after osteochondral injury in a large animal model.

基于重力的成骨因子模式，以在大型动物模型中骨软骨损伤后保留骨结构。

• 发表时间: 2022-07-05
• 影响因子: 9
• 作者: Zlotnick, Hannah M;Locke, Ryan C;Hemdev, Sanjana;Stoeckl, Brendan D;Gupta, Sachin;Peredo, Ana P;Steinberg, David R;Carey, James L;Lee, Daeyeon;Dodge, George R;Mauck, Robert L
• 通讯作者: Mauck, Robert L

Transient inhibition of meniscus cell migration following acute inflammatory challenge.

急性炎症挑战后半月板细胞迁移的短暂抑制。

• 发表时间: 2023-09
• 作者: Lemmon, Elisabeth A;Bonnevie, Edward D;Patel, Jay M;Miller, Liane M;Mauck, Robert L
• 通讯作者: Mauck, Robert L

Resorbable Pins to Enhance Scaffold Retention in a Porcine Chondral Defect Model.

可吸收的针增强猪软骨缺陷模型中的支架保留。

• 发表时间: 2021
• 影响因子: 2.8
• 作者: Patel, Jay M;Sennett, Mackenzie L;Martin, Anthony R;Saleh, Kamiel S;Eby, Michael R;Ashley, Blair S;Miller, Liane M;Dodge, George R;Burdick, Jason A;Carey, James L;Mauck, Robert L
• 通讯作者: Mauck, Robert L

Fabrication and maturation of integrated biphasic anatomic mesenchymal stromal cell-laden composite scaffolds for osteochondral repair and joint resurfacing.

用于骨软骨修复和关节表面重修的集成双相解剖间充质基质细胞负载复合支架的制造和成熟。

• 发表时间: 2021
• 作者: Fryhofer, George W;Zlotnick, Hannah M;Stoeckl, Brendan D;Farrell, Megan J;Steinberg, David R;Mauck, Robert L
• 通讯作者: Mauck, Robert L