Combined Gene Therapy/Tissue Engineered Cartilage Repair

描述（申请人逐字提供）：本I期方案的目的 目的是开发一种新的基因修复关节软骨的方法， 增强组织工程（GETE）。成功的临床修复关节 软骨仍然是难以捉摸的。目前的研究旨在修复关节 使用含有培养的骨膜细胞的构建体的软骨缺损 用IGF-1（胰岛素样生长因子）和BMP-7（骨形态发生因子）转导 蛋白质）基因作为双层植入物。作为生长因子， 由于这些生长因子具有促胰岛素样生长因子-1（IGF-1）和成骨因子（BMP-7）的特性，因此这些生长因子具有良好的生物相容性。 骨软骨缺损愈合的潜力。 已经开发了递送转导的祖细胞的组织构建体， 有IGF-1和BMP-7基因。技术和功效的进一步发展 将在一系列使用膝关节缺损的体内试验中进行评价 模型这些研究将集中在测试一种改进的，安全的， 修复关节表面的可重复方法。研究设计 开发该技术的方法如下：1）构建一个 用于递送IGF-1和BMP. 7基因的逆转录病毒表达系统。（二） 评估GETE基质作为IGF-1和BMP-7基因的递送载体。第三章 GETE技术评价软骨修复能力。的 用于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、胶原蛋白和 修复的软骨组织内的水含量，c）组织学 修复软骨的表征，和d）比较的材料性质 在模量和渗透性方面与正常软骨相似。 进一步的改进将是第二阶段研究的主题， 评价GETE技术在膝关节软骨缺损修复中的应用 在大型动物（绵羊）负重关节模型中。这种新方法使用 GETE技术应进一步扩大我们对软骨组织修复的认识 并且在未来可能具有重要的临床应用。 拟定商业应用： 目前尚无可靠且一致的方法用于关节面损伤的修复 软骨 根据大约500，000个案例，对此类器械的市场进行了估计 每年为受损软骨进行关节镜手术，价格约为2，000美元 对于美国市场来说，每个植入物意味着每年10.5亿美元的市场规模 一个人

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.