RI COBRE: CARTILAGE TISSUE ENGINEERING FOR JOINT REPAIR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景： 滑膜细胞是软骨组织工程可获得的细胞来源，可被转化生长因子-1刺激分化和合成软骨样基质，但目前还缺乏将实验室成功的前体细胞移植到体内环境中的报道。 滑膜细胞和其他间充质干细胞通常需要补充生长因子来诱导软骨形成，尤其是转化生长因子-1。其他生长因子如转化生长因子-β3、胰岛素样生长因子-1和骨形态发生蛋白也被用于在滑膜细胞或其他间充质干细胞诱导软骨生成。虽然在体外培养环境中可能会有新制备的生长因子溶液的成团添加，但体内生长因子的补充依赖于药物输送技术。可生物降解的聚合物释放系统通常用于随着时间的推移输送治疗性蛋白质和生长因子；然而，从PLGA微球释放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输送是软骨组织工程中的一大挑战。 研究目标： 该计划的目标是设计一种使用B型滑膜成纤维细胞(SF-B)和受控生长因子输送系统的软骨生物复合材料，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，可以使用滑膜细胞亚群(SF-B)构建基于细胞的工程化软骨生物复合材料，滑膜细胞亚群可以在生长因子的诱导下分化为软骨细胞。然而，产生具有更多生理生化、超微结构和机械性能的组织工程构建所需的生化和生物物理因素仍不清楚。由于天然软骨存在于低氧的微环境中，因此体外研究的重点是利用不同的氧气梯度构建软骨生物复合材料，以最大限度地促进软骨的形成。在体外研究的基础上，优化后的生物复合材料将在临床前的猪模型中进行测试。

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.