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大量的人类痛苦和巨大的社会和经济成本。虽然假体关节置换术是一种完善的手术，但有限的寿命使得这种治疗对年轻或活跃的个体来说是不可接受的，他们经常需要逐渐复杂的翻修手术。这个二期STTR的目标是开发一种骨软骨植入物，适合于髋关节骨关节炎股骨头的完全表面重建，并证明其与骨整合的能力。这项工作的两个新颖之处是：(i)在体外培养的短时间内加速骨软骨植入物的生成；（ii）整个关节的表面重塑，而不是局部缺陷。我们将在一个新的生物反应器中结合成人干细胞和三维编织支架，创造一个半球形软骨层，复制天然组织的承重特性。骨软骨植入物的体外生长将通过组织分子和生物力学测试进行量化，与重要骨骼的功能整合将通过免疫缺陷啮齿动物的皮下袋模型进行评估。这些新兴的再生医学技术的结合有望提供一种开发功能性、复杂的组织工程结构的新方法，这种结构可以修复受退行性疾病（如骨关节炎）影响的大块关节。

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.