It is well known that peripheral nerve constitutes a favorable environment for supporting axonal regeneration. However, the precise nature of cellular and non-cellular elements offering this support to the regenerating axons remains to be defined. Peripheral nerve grafts have been used to bridge long gaps in the injured peripheral nerve in experimental and clinical situations. The disadvantages of using nerve autograft (obtained from the same individual) is its limited availability and inevitable loss of function at the autograft location. Hence, nerve allografts obtained from other individuals have been utilized in nerve repair. We recently reported that acellular basal lamina allografts, lacking viable cells, exhibit reduced immunogenicity and were better tolerated by the host in comparison to cellular allografts. The rate and extent of axonal regeneration through acellular grafts was compromised in comparison to cellular grafts. The experiments proposed here will determine the role of Schwann cells and growth factor(s) on regeneration, in order to enhance axonal regeneration through acellular grafts. The hypothesis to be tested is that introduction of Schwann cell derivatives (i.e., growth factors) into acellular nerve segments can enhance their ability to support regeneration, and still maintain reduced immunogenicity. The underlying cellular processes involved in regeneration are also to be defined. Three independent strategies will be employed to modify the acellular grafts to enhance their regeneration supporting ability. These are: pretreatment of acellular nerves with nerve growth factor and ciliary neurotrophic factor, two factors known to influence neuronal survival and axonal growth; pretreatment of acellular nerves with soluble extract(s) prepared from peripheral nerve; and coculture of acellular nerves with Schwann cells. Inbred strains of rats will be used to determine the immunologic fate of grafted nerves, and to determine the extent of axonal regeneration through the various grafts by morphological and physiological methods. These results will define the role of specific growth factors and other treatments on the regeneration process through acellular basal lamina grafts. The findings may lead to the development of an ideal "bioprosthesis" for nerve gap repair, allowing maximum recovery after nerve injury.
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