Investigators: Gary S. Beaupré, PhD and Dennis R. Carter, PhD Project Staff: R. Lane Smith, PhD; Eric E. Sabelman, PhD; Stuart B. Goodman, MD, PhD; Nicholas Giori, MD, PhD; and Derek P. Lindsey, MS Project Categories: Arthritis / Osteoporosis - 2000 Purpose: 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. Background: 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. We believe that successful repair and regeneration of skeletal tissues in adults can be improved by guiding cell differentiation using tissue-specific biomechanical stimuli. The challenge is to translate cell and molecular level findings into clinically useful protocols using appropriate tissue and organ level models. The availability of valid models for tissue responses to mechanical stimuli will aid in identifying and overcoming potential shortcomings that presently limit long-term, successful regeneration in patients. Expected Outcomes: In this study we will develop experimental protocols and computational models that examine the mechanical influence on repair and regeneration of skeletal tissues. These models will be 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 is to develop protocols for repairing skeletal defects using autologous marrow-derived mesenchymal stem cells in patients. Funding Source: VA RR&D Merit Review Funding Status: Approved Letter of Intent |
