Evaluation of cross-linking procedures of collagen tubes used in peripheral nerve repair

Three different cross-linking methods were compared to prepare collagen tubes, namely irradiation by ultraviolet (UV), heating and immersing in glutaraldehyde (GA). Bridge grafting of 15 mm was carried out with these tubes, as well as with non-cross-linked collagen tubes for comparison, in a defect of rat sciatic nerves (N=21 in each group). As a control, isografting was carried out (N=6). The specimens were taken from the grafted site in each experimental group for histological observation after, respectively 1, 2, 4, 6 and 8 weeks (N=3 each). Evoked muscle action potentials were recorded on the calf muscle in the experimental and control groups after 12 weeks, and the grafted material and tibial nerve were harvested for histological analysis (N=6). The inner space of UV-irradiated tubes was preserved with almost no cell infiltration and nerve regeneration matching for isograft was obtained. Rapid degradation of the heat-treated tubes occurred and many macrophages were mobilized to remove the collagen debris. The non-treated tube swelled and the regenerated nerve tissue in the tube was constricted with time. The GA-immersed tubes showed less cellular activity and poor regenerated nerve tissue compared with the other cross-linking methods. Therefore, UV irradiation to collagen tubes is recommended as a cross-linking method for nerve conduit.