NERVE REPAIR BY SYNTHETIC AND BIOLOGICAL POLYMERS

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DESCRIPTION (provided by applicant): Presently, there are no effective therapies to restore function of nerves traumatized by mechanical cleavage. By applying a biocompatible and synthetic polymer, polyethylene glycol (PEG), the investigators have successfully restored the conduction of compound action potentials (CAP) in severed guinea pig spinal cord and peripheral nerves in vitro. However, the technique would not be successful for similar injuries in vivo due to the mechanical instability of the nerve trunk. The investigators are attempting to achieve mechanically stable nerve fusion by adhesively bonding the nerve connective tissue using surgical adhesives . Specifically, they will use two commercially available surgical adhesives and one experimental adhesive for anastomosing the severed nerve trunks after PEG-fusion of the cell membranes in an isolated sciatic nerve transection model. Their preliminary experiments with animal (guinea pig) connective tissue indicate that these adhesives would be able to provide the required mechanical stability to a new fused nerve trunk in vivo. The commercial adhesives used in the study (fibrin and cyanoacrylate) have been used in general surgery with manageable immune response. The experimental adhesive (Mussel Adhesive Protein) has been shown in published literature to elicit minimal immune response. The strong adhesive performance and reasonable biocompatibility of these adhesives compel the investigators to believe that these surgical adhesives are ideal candidates for nerve fusion studies using PEG. Their study will lay the groundwork for subsequent in vivo studies with guinea pigs. Use of surgical adhesives will enable PEG repair of transected nerves in vivo, which in turn will improve the post-injury quality of life of nerve-trauma victims. As part of the investigation, mechanical, electrophysiological and histological tests will be performed on uninjured guinea pig sciatic nerves to determine the critical functional tensile load (CFTL) of the nerve. ln the experiments, surgical adhesives will be used in conjunction with PEG on isolated and completely severed sciatic nerves, and the optimal conditions for PEG/surgical adhesive nerve fusion will be determined. Each surgical adhesive system will be evaluated using CFTL values as a standard for comparison. In addition, comparative immunological performance of each adhesive will also be determined using established procedures. Frequent consultation with a neurosurgeon, who is a member of the research team, will provide necessary input to direct the study and experiments towards clinically relevant solutions for transection nerve injuries.