There is accumulating evidence that the healing process of an injured organ in the adult mammal can be modified to yield a partly or wholly regenerated organ. The majority of the evidence has originally come from studies of skin regeneration, peripheral nerve regeneration and conjunctiva regeneration. Recently, progress has been reported in several laboratories in studies of regeneration of other organs, including heart valves, urological organs, bone and the spinal cord. In the proposed study the mechanism of induction of regeneration will be studied in the peripheral nervous system. Recently obtained evidence shows that during healing of the transected rat sciatic nerve, contractile fibroblasts organize in a capsule that surrounds the regenerating nerve. The data suggest that these contractile fibroblasts compress the regenerating nerve, limiting development of a near normal diameter. This data further suggests that use of scaffolds that induces thinning of this capsule is expected to weaken contractile forces, enhancing the quality of regeneration. Blocking of the contraction process in healing peripheral nerves in rats will be studied primarily using scaffolds that disorganize contractile cells, preventing their organization. Pharmacological agents that block synthesis of a-smooth muscle actin will also be employed. The structure of the regenerating nerve will be studied in part by new methodology that will be adapted to the injured peripheral nervous system: two-photon microscopy and second harmonic generation. An attempt will be made to elucidate the mechanism of contraction blocking during healing of injured nerves, and to find out an association, if any, with induced regeneration. Blocking of the contraction process in healing peripheral nerves in rats will be studied primarily using scaffolds that disorganize contractile cells, preventing their organization. Pharmacological agents that block synthesis of a-smooth muscle action will also be employed. The structure of the regenerating nerve will be studied in part by new methodology that will be adapted to the injured peripheral nervous system: two-photon microscopy and second harmonic generation. An attempt will be made to elucidate the mechanism of contraction blocking during healing of injured nerves, and to find out an association, if any, with induced regeneration.
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