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.
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