RI COBRE: CARTILAGE TISSUE ENGINEERING FOR JOINT REPAIR

RI COBRE：用于关节修复的软骨组织工程

• 批准号: 7959907
• 负责人: DEBORAH McK. CIOMBOR
• 金额: $ 15.26万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959907
• 关键词: Cartilage; Cells; Centers of Research Excellence; Chondrogenesis; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Encapsulated; Engineering; Environment; Funding; Gene Expression; Grant; Growth Factor; Healed; Health; Human; Hypoxia; Implant; Institution; Joint repair; Joints; Laboratories; Microspheres; Musculoskeletal; Organ; Osteoblasts; Oxygen; Oxygen measurement, partial pressure, arterial; Polymers; Proliferating; Research; Research Personnel; Resources; Source; Synovial Cell; System; Techniques; Therapeutic Intervention; Tissue Engineering; Tissues; United States National Institutes of Health; base; bone; controlled release; cost; healing; in vivo Model; loss of function; repaired; response; scaffold; skeletal

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.

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。 近年来，对用于治疗肌肉骨骼损伤的治疗性干预，特别是修复或替换受损软骨的需求急剧增加。目前可用的软骨修复技术具有局限性，包括有限的愈合、高成本、导致功能丧失的组织植入物的分解以及有能力的细胞组分的有限可用性。软骨修复的治疗性干预，包括基于细胞的工程修复，需要了解生长因子的调节作用以及与物理力协同作用的潜力。 在发育过程中，感受态细胞暴露于生长因子的空间和时间梯度，并在反应中增殖或分化，产生复杂的组织和器官。此外，发育中的组织暴露于不断变化的微环境中，其中包括不同的氧张力。我们实验室的初步数据表明：1）滑膜细胞可被诱导，在一种生长因子TGFIS的时间梯度作用下发生软骨形成。2)在包封的聚合物微球和/或支架中生长因子序列的受控释放可以概括生长因子表达的发育序列，和3）来源于在TKR时去除的人骨的成骨细胞通过改变它们的基因表达谱来响应不同的缺氧条件。在这里提出的研究中采取的方法探索了使用受控的氧气环境来确定组织工程构建体对其物理微环境变化的反应。的 这里提出的研究将表征这些软骨祖细胞对许多相关生长因子的反应，并将确定它们在模拟正常关节的氧梯度的系统中的最佳浓度。我们将利用这些信息来进一步检查所产生的工程构建体 关节修复的体内模型中的软骨。