Combined Gene Therapy/Tissue Engineered Cartilage Repair

描述(来自申请人的逐字)：该第一阶段协议的目标 是开发一种利用基因修复关节软骨的新方法 增强型组织工程(GETE)。关节修复术临床成功 软骨仍然难以捉摸。目前的研究试图修复关节 含有培养的骨膜细胞构建物修复软骨缺损 胰岛素样生长因子L和骨形态发生蛋白-7的转导 蛋白质)基因作为双层植入物。作为生长因子具有很强的软骨形成能力 (胰岛素样生长因子-L)和成骨(骨形态发生蛋白-7)的特性，这些生长因子都有良好的 在骨软骨缺损处修复的潜力。 已经开发出将祖细胞转导的组织结构 携带胰岛素样生长因子-L和骨形态发生蛋白-7基因。技术和功效的进一步发展 将在使用Lapine膝关节缺陷的一系列体内测试中进行评估 模特。这些研究将集中于测试改进的、安全的和 可重复使用的关节表面修复方法。研究设计 发展该技术的方法如下：1)建设一个 携带胰岛素样生长因子-L和骨形态发生蛋白7基因的逆转录病毒表达系统2) GETE基质作为胰岛素样生长因子-L和骨形态发生蛋白-7基因载体的评价。3) 应用GETE技术评价软骨修复能力。这个 评估软骨修复的参数包括：a)胶原分型为 与正常软骨相比，b)GAG、胶原和 修复的软骨组织内的水分含量，c)组织学 修复的软骨的表征，以及d)材料性能的比较 在弹性和渗透性方面与正常软骨相似。 进一步的改进将是第一阶段研究的主题，该研究将 GETE技术在膝关节软骨缺损修复中的应用 在大型动物(羊)承重关节模型中。这一新方法使用 GETE技术将进一步扩大我们对软骨组织修复的了解 并可能在未来有重要的临床应用。 建议的商业应用： 目前尚无可靠、一致的方法用于关节修复 软骨。基于大约500,000个案例的此类设备的估计市场 每年为受损的软骨进行关节镜手术，费用约为2,000美元 每个植入物对美国市场来说意味着每年10.5亿美元的市场规模 独自一人。

DESCRIPTION (Verbatim from Applicant): The objective of this Phase I protocol is to develop a novel approach for the repair of articular cartilage using gene enhanced tissue engineering (GETE). Successful clinical repair of articular cartilage continues to be elusive. The current study seeks to repair articular cartilage defects using constructs containing cultured periosteal cells transduced with IGF-l (insulin-like growth factor) and BMP-7 (bone morphogenic protein) genes as a bilayer implant. As growth factors with strong chondrogenic (IGF-l) and osteogenic (BMP-7) properties, these growth factors have good potential in the healing of osteochondral defects. Tissue constructs have been developed which deliver progenitor cells transduced with IGF-l and BMP-7 genes. Further development of the technology and efficacy will be evaluated in a series of in vivo tests using a lapine knee defect model. These studies will focus on the testing of an improved, safe, and reproducible approach to the repair of joint surfaces. The research design methods to develop the technology are as follows: 1) Construction of a retroviral expression system for delivery of IGF-l and BMP.7 genes. 2) Evaluation of GETE matrices as delivery vehicles for IGF-l and BMP-7 genes. 3) Evaluation of the cartilage reparative capacity using the GETE technology. The parameters for evaluating cartilage repair include: a) Collagen typing as compared to normal cartilage, b) Biochemical measurements of GAG, collagen, and water content within the repaired cartilage tissue, c) Histological characterization of the repaired cartilage, and d) Material properties compared to normal cartilage with respect to modulus and permeability. Further refinements will be the subject of a Phase Il study, which would evaluate this GETE technology in the repair of knee articular cartilage defects in a large animal (sheep) weight bearing joint model. This novel approach using GETE technology should further expand our knowledge of cartilage tissue repair and may have important clinical applications in the future. PROPOSED COMMERCIAL APPLICATION: There is no currently reliable and consistent method used for the repair of articular cartilage. The estimated market for such a device based on approximately 500,000 cases of arthroscopic surgery for damaged cartilage done per year with a price of about $2,000 per implant would mean a market size of 1.05 billion dollars a year for the U.S. market alone.