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。 近年来，对治疗肌肉骨骼损伤，特别是修复或替换受损软骨的治疗干预的需求急剧增加。目前可用的软骨修复技术具有局限性，包括愈合有限、成本高、组织植入物破裂导致功能丧失以及可获得的合格细胞成分有限。对软骨修复的治疗干预，包括基于细胞的工程化修复，需要了解生长因子的调节作用以及与物理力量协同作用的潜力。 在发育过程中，有能力的细胞暴露在生长因子的空间和时间梯度下，并相应地增殖或分化，创造复杂的组织和器官。此外，发育中的组织暴露在不断变化的微环境中，其中包括不同的氧气压力。我们实验室的初步数据表明，1)滑膜细胞可以根据一种生长因子TGFIS的时间梯度被诱导成软骨；2)一系列生长因子在包裹的聚合物微球和/或支架中的受控释放可以概括生长因子表达的发育序列；3)从TKR取出的人骨来源的成骨细胞通过改变它们的基因表达谱来应对不同的缺氧条件。在这里提出的研究中采用的方法探索了利用受控氧气环境来确定组织工程构建物对其物理微环境变化的反应。这个 这里提出的研究将描述这些软骨前体细胞对一些相关生长因子的反应，并将确定它们在模拟正常关节的氧气梯度的系统中的最佳浓度。我们将使用此信息进一步检查产生的工程构造 关节修复的活体模型中的软骨。

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. The demand for therapeutic interventions for the treatment of musculoskeletal damage, especially repair or replacement of damaged cartilage, has increased dramatically in recent years. Currently available cartilage repair techniques have limitations, including limited healing, high cost, breakdown of the tissue implant leading to loss of function, and limited availability of competent cellular components. Therapeutic intervention for the repair of cartilage, including cell-based engineered repair, requires an understanding of the regulatory effects of growth factors and the potential for synergies with physical forces. In development, competent cells are exposed to spatial and temporal gradients of growth factors and proliferate or differentiate in response, creating complex tissues and organs. Addtionally, the developing tissues are exposed to a changing microenvironment, which includes varying oxygen tensions. Preliminary data in our laboratory has shown that 1) synovial cells can be induced to undergo chondrogenesis in response to a temporal gradient of one growth factor, TGFIS.; 2) that the controlled release of a sequence of growth factors in encapsulated polymer microspheres and/or scaffolds can recapitulate developmental sequences of growth factor expression and 3) that osteoblasts derived from human bone removed at TKR respond to varying conditions of hypoxia by changing their profile of gene expression. The approach taken in studies proposed here explores the use of controlled oxygen environments to determine the response of tissue engineered constructs to changes in their physical microenvironment. The studies proposed here will characterize the response of these chondroprogenitor cells to a number of relevant growth factors and will define their optimum concentrations in a system which will mimic the oxygen gradients of a normal joint. We will use this information to further examine the resulting engineered construct of cartilage in an in vivo model of joint repair.