Principal Investigators: Dennis R. Carter, PhD and Gary S. Beaupré, PhD Investigators: Kelvin W. Li, PhD; R. Lane Smith, PhD; Derek P. Lindsey, MS; Stuart B. Goodman, MD, PhD; Nicholas J. Giori, MD, PhD Project Category: Bone & Joint - 2005 The proposed project will consist of a series of complementary experimental and computational studies that examine the role of mechanical stimuli in the repair and regeneration of bone, cartilage, and tendon defects. The goal of this work is to develop tissue-specific loading protocols to guide and enhance the tissue repair and regeneration process. The founding hypothesis for our study is that differentiation of mesenchymal stem cells can be directed in a predictable way by the local mechanical environment to achieve tissue and organ-specific specialization. The results of the proposed study will provide an important link between cell-based studies and clinical rehabilitation techniques. Guided regeneration will unquestionably become an important component of future treatments for skeletal diseases such as osteoporosis and osteoarthritis. A primary function of skeletal tissues is a mechanical one related to locomotion, manipulation, and structural support. The sensitivity of skeletal tissues to mechanical stimuli is in large part responsible for the exquisite relationship between function and morphology that all skeletal tissues attain. Sensitivity to mechanical stimuli also plays a central role in tissue repair and regeneration that occurs during physical rehabilitation, with fracture healing as an example of a prototypical regeneration process. In this study we developed experimental protocols and computational models to examine the mechanical influence on repair and regeneration of skeletal tissues. These models were used to identify the limitations of current tissue regeneration techniques and to develop guidelines for improving the long-term success of bone, cartilage and tendon regeneration. The ultimate clinical goal of this project is to develop protocols for repairing skeletal defects using autologous marrow-derived mesenchymal stem cells in patients. Recent Publications: Li KW, Lindsey DP, Wagner DR, Giori NJ, Schurman DJ, Goodman SB, Smith RL, Carter DR, Beaupre GS: Mechanobiological influences on tissue-engineered tendon implants in vitro. Trans Orthop Res Soc 30:399, 2005. Li KW, Lindsey DP, Wagner DR, Giori NJ, Schurman DJ, Goodman SB, Smith RL, Carter DR, Beaupre GS: Gene Regulation Ex Vivo Within a Wrap-Around Tendon. Conditionally accepted to: Tissue Engineering, June, 2005. Funding Source: VA Merit Review Funding Status: Completed
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