The Overall Aim of the Program Project is to understand the biology of the regeneration and transplantation of mammalian skeletal muscle and contribute to improvements in reconstructive surgical procedures involving skeletal muscles. Experiments focus on two significant biological and clinical questions: A) In previously denervated muscles in rats, what factors affect the recovery of structural and functional properties of upon reinnervation? and B) In stabilized free neurovascular-repaired grafts in cats, what mechanisms are responsible for the deficits in structural and functional properties produced by tendon and nerve repair. The properties of the graft are expected to be related to the physical activity of the host cat. We hypothesize that structural and functional properties of reinnervated single muscle fibers in grafts of normal muscle and short-term denervated muscles will not differ from those of single muscle fibers in control muscles, but that differentiation of regenerated muscle fibers derived from long-term denervated muscles will be incomplete. Each of the three projects will have specific responsibilities directed toward the testing of the Group and Individual Hypotheses. The responsibilities will be morphological studies (Project 1), physical activity of host animals and protein analyses of grafts and muscles (Project 2), and muscle mechanics of single fibers, motor units, and whole grafts and muscles (Project 3). An Administrative Core will provide support services, an Animal Core will perform the transplantation operations and post-operative care, and a Statistical Core will provide appropriate statistical procedures and consultant services. The significance of the proposed studies is the resolution of two major clinical problems: 1. determination of the optimum conditions for denervated muscle to regain structure and function upon reinnervation; and 2. clarification of the operative procedures and underlying mechanisms responsible for deficits in large stabilized free neurovascular-repaired grafts.
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