RI COBRE: CARTILAGE TISSUE ENGINEERING FOR JOINT REPAIR

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景资料： 滑膜细胞是软骨组织工程的一种可行的、可获得的细胞来源，并且可以被转化生长因子-1（TGF-1）刺激以分化和合成软骨样基质，然而，缺乏将实验室成功的前体细胞转化为体内环境。 滑膜细胞和其他间充质干细胞通常需要补充生长因子以诱导软骨形成，特别是TGF-β 1。其他生长因子如TGF-β 3、胰岛素样生长因子-1（IGF-1）和骨形态发生蛋白也已用于诱导滑膜细胞或其他间充质干细胞中的软骨形成。虽然在体外培养环境中可以快速加入新鲜制备的生长因子溶液，但体内生长因子的补充依赖于药物递送技术。可生物降解的聚合物释放系统通常用于随时间递送治疗性蛋白质和生长因子;然而，从PLGA微球递送的特征是提供蛋白质的初始爆发，随后很少或没有释放。长时间可控的生长因子递送是软骨组织工程中的一个巨大挑战。 研究目标： 该计划的目标是设计一种软骨生物复合材料，该复合材料采用B型滑膜成纤维细胞（SF-B）和受控生长因子递送系统，以促进软骨的功能修复和再生，用于受损关节的康复。 这项研究的总体假设是，基于细胞的工程化软骨生物复合材料可以使用滑膜细胞（SF-B）的亚群来创建，其可以通过生长因子诱导分化为软骨细胞。然而，产生具有更多生理生化、超微结构和机械特性的组织工程构建体所必需的生物化学和生物物理因素仍然未知。由于天然软骨存在于缺氧的微环境中，因此体外研究的重点是使用不同的氧梯度来最大化软骨形成来构建软骨生物复合材料。在体外研究的基础上，将在临床前猪模型中测试优化的生物复合材料。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Synoviocytes are a viable, accessible cell source for cartilage tissue engineering and can be stimulated by transforming growth factor-¿1 (TGF-¿1) to differentiate and synthesize cartilage-like matrix, however the translation of the laboratory success with precursor cells to the in vivo circumstance has been lacking. Synoviocytes and other mesenchymal stem cells typically require supplementation with growth factors to induce chondrogenesis, especially TGF-¿1. Other growth factors such as TGF-¿3, insulin-like growth factor-1 (IGF-1) and bone morphogenetic proteins have also been used to induce chondrogenesis in synovial cells or other mesenchymal stem cells. While bolus additions of freshly prepared growth factor solutions may be possible in in vitro culture settings, supplementation of growth factors in vivo relies on drug delivery techniques. Biodegradable polymer release systems are commonly used for the delivery of therapeutic proteins and growth factors over time; however, delivery from PLGA microspheres characteristically provides an initial burst of the protein, followed by little or no release. Controlled growth factor delivery for prolonged periods of time is a great challenge in cartilage tissue engineering. Research Goals: The goal of this program is to engineer a cartilage biocomposite that employs type-B synovial fibroblasts (SF-B) and a controlled growth factor delivery system to promote functional repair and regeneration of cartilage, for rehabilitation of damaged joints. The overall hypothesis of this study is that cell-based engineered cartilage biocomposites can be created using a sub-population of synoviocytes (SF-B), which can be induced by growth factors to differentiate into chondrocytes. However, both the biochemical and the biophysical factors that are necessary to produce a tissue engineered construct with more physiologic biochemical, ultra-structural and mechanical properties remain unknown. Because native cartilage exists in a hypoxic microenvironment, the emphasis of the in vitro studies is on the construction of a cartilage biocomposite using varied oxygen gradients to maximize chondrogenesis. Building on the in vitro studies, an optimized biocomposite will be tested in a pre-clinical porcine model.