Tissue engineered osteochondral patella resurfacing

描述(申请人提供)：拟议研究的目标是开发一种组织工程化的骨软骨结构，将导致狗的整个膝盖骨关节表面的功能性重新铺设。我们的长期目标是开发一种临床适用的生物关节成形术方法来治疗人类因损伤或骨关节炎造成的关节软骨丢失。关节软骨对侮辱和损伤的自然反应是多种多样的，充其量是不令人满意的。目前解决这种不满意反应的外科方法包括人工关节成形术、自体或同种异体移植和组织刺激技术。不幸的是，目前的治疗选择受到假体磨损、松动和感染、可用性、集成度差以及解剖尺寸和形状匹配差的限制。这些限制导致功能障碍、残疾、发病率以及患者、医疗保健行业、政府机构和纳税人的经济和情感成本。克服这些问题的一个潜在方法是开发与患者匹配的组织工程化骨软骨结构，这些结构将使受影响的整个关节表面重新浮出水面(S)。通过我们团队的合作伙伴关系进行的初步工作表明，可以使用先进的成像技术、成熟的软骨细胞培养技术和体外组织工程方法来创建功能性骨软骨结构。此外，可以使用同种异体软骨细胞创建这些结构，并成功地将其植入狗膝盖的关节软骨缺损处，从而产生组织存活和整合。基于这些数据，我们假设可以创建组织工程化的骨软骨结构，以允许对狗的整个膝盖骨关节表面进行功能性表面重铺，通过跛行评分、临床成像、生化、生物力学和组织学结果测量进行评估。在验证这一假设时，我们的具体目标是：1)使用定义明确的培养液和生长因子补充优化犬骨软骨结构的体外培养，以用于体内软骨表面的重建；2)评估将工程化的骨软骨结构植入成年狗膝盖的体内植入。这些目标的完成将为实现我们所宣布的长期目标奠定基础，这将有可能为修复患者的大型关节软骨缺陷提供临床工具，从而推迟甚至消除人工关节成形术的需要。

DESCRIPTION (provided by applicant): The goal of the proposed research is to develop a tissue-engineered osteochondral construct that will result in functional resurfacing of the entire articular surface of the patella in dogs. Our long-term objective is to develop a clinically applicable biologic arthroplasty approach for treating articular cartilage loss due to injury or osteoarthritis in humans. The natural response of articular cartilage to insult and injury is variable and, at best, unsatisfactory. Current surgical approaches for addressing this unsatisfactory response involve synthetic arthroplasty, autogenous or allogeneic grafts, and tissue stimulation techniques. Unfortunately, current treatment options are limited by prosthetic wear, loosening, and infection, availability, poor integration, and poor anatomic size and shape matching. These limitations results in dysfunction, disability, morbidity, and financial and emotional costs to patients, the health-care industry, government agencies, and tax-payers. A potential means for overcoming these issues is to develop tissue-engineered osteochondral constructs matched to patients that will resurface the entire articular surface(s) affected. Initial work through our group's collaborative partnership suggests that functional osteochondral constructs can be created using advanced imaging, established chondrocyte culture techniques, and in vitro tissue engineering methodology. Further, these constructs can be created using allogeneic chondrocytes and be successfully implanted into articular cartilage defects in the knees of dogs, resulting in tissue viability and integration. Based on these data, we hypothesized that tissue-engineered osteochondral constructs can be created that will allow for functional resurfacing of the entire articular surface of the patella in dogs as assessed by lameness scoring, clinical imaging, biochemical, biomechanical, and histologic outcome measures. In testing this hypothesis, our specific aims are to: 1) Optimize in vitro culture of canine osteochondral constructs using a well-defined culture medium and growth factor supplementation for in vivo cartilage resurfacing of the patella, and 2) Assess in vivo implantation of engineered patellar osteochondral constructs implanted into knees of adult dogs. Completion of these aims will provide the basis for pursuing our stated long-term objective, which will have the potential for providing a clinical tool for repair of large articular cartilage defects in patients thereby delaying, or even eliminating, the need for artificial joint arthoplasty.