The slow rate, incomplete extent, and poor specificity of axonal regeneration is an important medical problem associated with significant dysfunction and loss of productivity. Our long term goal is to develop techniques using polymers to improve the rate, extent, and/or specificity of nerve axon regeneration in humans. To begin at attain this goal, in this application we propose to use a biopolymer hydrogel which we have recently developed as substitute for microsuture to hold together the stumps of severed nerved bundles (Specific Aim I). We expect that this hydrogel will produce greater regenerative success than microsuture in vivo because the hydrogel causes less tissue damage. We also propose to use a biopolymer (polyethylene glycol) in hypotonic salines with reduced calcium to fuse (reconnect) the severed halves of crushed nerve axons within minutes in vitro (Specific Aim II). Finally, we propose to use our recently developed biopolymer hydrogel to add mechanical strength to axons reconnected by polyethylene glycol in vivo (Specific Aim III). This biopolymer-based technique would increase the rate (and perhaps the extent) of reconnection of severed axons with denervated tissues. We will assess the ability of these biopolymer to improve the rate, extent, and specificity of regeneration of rat sciatic axons according to morphological criteria (axolemma and axoplasmic continuity in electron micrographs, diffusion of tracers). electrophysiological criteria (conductio of action potentials), and behavioral criteria (sciatic functional index). Given that traumatic injuries to nerve axons are rather common and axonal integrity is essential for proper neuronal function , successful development of one or more of these proposed techniques using biopolymer to improve axonal regeneration would have significant medical implications for humans.
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