This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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. Thestudies 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 constructof cartilage in an in vivo model of joint repair.
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