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.

摘要 关节软骨衬骨关节表面，并有效地传递高应力， 与日常生活的活动。然而，对这种组织的损伤非常普遍，约9%的美国人 年龄在30岁及以上的患有髋关节或膝关节骨关节炎（OA）的人群。这对许多人产生了不利影响。 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，并降低了他们的生活质量。 整体生活质量。不幸的是，对于受损的患者，几乎没有可行的治疗选择。 关节软骨，最最终在关节置换与金属和塑料假体，这是容易 最终需要翻修手术。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，并提供支持性的 细胞外基质沉积和软骨样组织功能成熟的环境，两者都在体外 以及我们尤卡坦小型猪软骨修复的大型动物模型。此外，我们最近证明， 活的、工程化的软骨构建体可以形成模拟复合体的解剖结构， 原生关节表面的几何形状。我们还开发了一种技术， 固定和活体植入物与现有骨的体内整合。在本提案中，我们利用这一点 在实现生物关节表面置换的“圣杯”方面取得进展： 关节软骨面我们的实验将使用尤卡坦小型猪的股骨髁作为模型， 将通过复杂的和临床相关的结果测量来评估成功。一旦在此验证， 在临床前环境中，该技术可以直接转化为人类临床试验，并扩展到其他领域。 身体的关节。最终，这项工作可能有一天会消除对金属关节置换的需要， 塑料和减轻OA在退伍军人群体以及整个社会中的严重影响。

项目成果

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

• DOI: 10.1088/1758-5090/ac3acb
• 发表时间: 2021-12-01
• 期刊: Biofabrication
• 影响因子: 9
• 作者: Galarraga JH;Locke RC;Witherel CE;Stoeckl BD;Castilho M;Mauck RL;Malda J;Levato R;Burdick JA
• 通讯作者: Burdick JA

The porcine accessory carpal bone as a model for biologic joint replacement for trapeziometacarpal osteoarthritis.

• DOI: 10.1016/j.actbio.2021.05.011
• 发表时间: 2021-07-15
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Stoeckl BD;Zlotnick HM;Farrell MJ;Fryhofer GW;Hast MW;Miller LM;Sennett ML;Baxter JR;Schaer TP;Mauck RL;Steinberg DR
• 通讯作者: Steinberg DR

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

• DOI: 10.1002/jor.24969
• 发表时间: 2021-11
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Fryhofer GW;Zlotnick HM;Stoeckl BD;Farrell MJ;Steinberg DR;Mauck RL
• 通讯作者: Mauck RL

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。

• DOI: 10.1177/1947603520962568
• 发表时间: 2021
• 期刊: Cartilage
• 影响因子: 2.8
• 作者: Patel,JayM;Sennett,MackenzieL;Martin,AnthonyR;Saleh,KamielS;Eby,MichaelR;Ashley,BlairS;Miller,LianeM;Dodge,GeorgeR;Burdick,JasonA;Carey,JamesL;Mauck,RobertL
• 通讯作者: Mauck,RobertL

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

• DOI: 10.1088/1758-5090/ac79cd
• 发表时间: 2022-07-05
• 期刊: BIOFABRICATION
• 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.