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。第一阶段STTR的目标是开发一种适合于人类髋关节骨关节炎股骨头完全置换的植入物，并通过使用干细胞和模拟软骨支架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机械功能软骨的生成；（ii）整个关节的表面重塑，而不是局部缺陷。我们将创造一个半球形的软骨层，通过结合成人干细胞和由新的三维（3D）编织技术和一种新颖的、高度可扩展的细胞培养装置制成的生物材料支架，复制天然组织的承重特性。工程组织的成熟和生长将通过非破坏性MRI和生物力学测试来监测，并将使用免疫缺陷啮齿动物的皮下袋模型来评估与重要骨骼的功能整合。这些新兴再生医学技术的结合有望提供一种开发功能性组织工程结构的新方法，从而提高软骨修复手术的成功率。

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 I STTR is to develop an implant suitable for complete resurfacing of an osteoarthritic femoral head of the human hip joint and proven ability to integrate with bone by using stem cells and a cartilage-mimetic scaffold. The two novelties of this work are: (i) accelerated generation of mechanically functional cartilage 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 biomaterial scaffold made by a new three-dimensional (3D) weaving technology and a novel, highly scalable cell culture device. Maturation and growth of the engineered tissue will be monitored by non-destructive MRI 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 tissue engineered constructs that can improve the success of cartilage repair procedures. This project represents a Phase I STTR to combine adult human stem cell and three-dimensional weaving technologies to create a layer of cartilage that can integrate with bone. The two primary novelties of this work are: (i) accelerated generation of mechanically functional cartilage within a brief period of in vitro culture and (ii) resurfacing of an entire joint instead of a focal defect. The ultimate goal of this study is to develop a tissue engineering approach that can be used to resurface large segments of the joint that have been affected by degenerative diseases such as osteoarthritis.