Hip-Joint Resurfacing with Functional Human Cartilage

描述（由申请人提供）：退行性关节疾病造成了巨大的社会和经济代价。虽然人工关节置换术是一种成熟的手术，但有限的寿命使得这种治疗对于年轻或活跃的个体来说是不可接受的，他们经常需要进行复杂的翻修手术。本II期STTR的目标是开发一种骨软骨植入物，适用于髋关节骨关节炎股骨头的完全表面置换，并证明其与骨整合的能力。这项工作的两个新颖之处是：（i）在体外培养的短暂时间内加速生成骨软骨植入物，以及（ii）整个关节的表面置换，而不是局部缺损。我们将在一个新的生物反应器中将成人干细胞与三维编织支架结合，创造一个半球形软骨层，复制天然组织的承重特性。将通过组织分子和生物力学试验对骨软骨植入物的体外生长进行定量，并使用免疫缺陷啮齿动物的皮下囊袋模型评估与活骨的功能整合。这些新兴的再生医疗技术的结合有望提供一种新的手段来开发功能性的、复杂的组织工程化结构，这些结构可以重新修复受退行性疾病（如骨关节炎）影响的大段关节。 公共卫生相关性：该项目是一个II期STTR项目，旨在开发一种新型组织工程方法，以创建用于关节表面置换的骨软骨植入物，作为髋关节骨关节炎的治疗方法。技术基础涉及在解剖学形状的三维编织支架上生长的成人间充质干细胞的组合，该支架在新型生物反应器系统中培养，可以加速机械功能软骨的产生。本研究的最终目标是开发一种组织工程方法，可用于重新修复受退行性疾病（如骨关节炎）影响的大段关节。

DESCRIPTION (provided by applicant): Degenerative joint disease accounts for substantial human suffering at tremendous social and economic cost. While prosthetic joint replacement is a well-established procedure, a finite life span makes this treatment unacceptable for younger or active individuals who often require progressively complicated revision surgeries. The goal of this Phase II STTR is to develop an osteochondral implant suitable for complete resurfacing of the osteoarthritic femoral head of the hip joint and proven ability to integrate with bone. The two novelties of this work are: (i) accelerated generation of an osteochondral implant within a brief period of in vitro culture and (ii) resurfacing of an entire joint instead of a focal defect. We will create a hemispherical layer of cartilage that replicates the load-bearing properties of the native tissue by combining adult human stem cells with a three- dimensionally woven scaffold in a new bioreactor. In vitro growth of the osteochondral implant will be quantified by histomolecular and biomechanical testing, and functional integration with vital bone will be assessed using a subcutaneous pouch model in an immunodeficient rodent. The combination of these emergent regenerative medical technologies is expected to provide a novel means of developing functional, complex tissue engineered constructs that can resurface large segments of joints that have been affected by degenerative diseases such as osteoarthritis. PUBLIC HEALTH RELEVANCE: This project represents a Phase II STTR project to develop a novel tissue engineering approach to create osteochondral implants for joint resurfacing as a treatment for hip osteoarthritis. The technologic basis involves a combination of adult human mesenchymal stem cells grown on an anatomically shaped, three-dimensionally woven scaffold, which is cultured in a novel bioreactor system that can accelerate the generation of mechanically functional cartilage. The ultimate goal of this study is to develop a tissue engineering approach that can be used to resurface large segments of joints that have been affected by degenerative diseases such as osteoarthritis.