Alignment of collagen and laminin-containing gels improve nerve regeneration within silicone tubes.

PURPOSE: Placement of extracellular matrix components has been used as a mean to enhance axonal growth across nerve long gaps repaired by tubulization. However, such matrices may impede axonal regeneration depending on its density and microgeometry. METHODS: Silicone tubes were prefilled with collagen or laminin-containing gels and implanted into a 6 mm gap, a length considered limiting for regeneration, in the mouse sciatic nerve. Gels were polymerized prior to implantation either in horizontal position or subjected to gravitational (in vertical position) or to magnetic forces to induce longitudinal alignment of the fibrils. Recovery of motor, sensory and sudomotor functions in the hindpaw was evaluated during 4 months postoperation. RESULTS: Reinnervation started earlier and achieved slightly higher levels with aligned collagen gels than with the horizontal gel. For the three groups repaired with tubes with Matrigel, there was a gradation of the functional results, reinnervation started earlier and reached higher values in matrix with magnetically-induced, longitudinal orientation than with the horizontal gel, whereas gravitational alignment followed an intermediate evolution. Final morphological evaluation showed more dense residual mass of collagen than of Matrigel at the center of the regenerate nerves. The number of myelinated fibers was increased in tubes with alignment compared to horizontal gels. CONCLUSIONS: Alignment of collagen and laminin gels within a silicone tube increases the success and the quality of regeneration in long nerve gaps. The laminin gel performed better than the collagen gel under each condition tested. The combination of an aligned matrix with embedded Schwann cells should be considered in further steps for the development of an artificial nerve graft for clinical application.

Improvement of regeneration with predegenerated nerve transplants in silicone chambers.

We compared regeneration and reinnervation of target organs after sciatic nerve resection and repair with silicone tubes filled with saline solution or with a peroneal nerve segment as a nerve transplant versus an autologous sciatic nerve graft leaving either 4 mm or 6 mm gaps. The aims of this study were to evaluate the effects of predegeneration and donor immunogenicity of nerve transplants. Functional reinnervation was assessed by noninvasive methods to determine recovery of sweating, sensory and motor functions in the hindpaw after three months postoperation for 4 mm and four months postoperation for 6 mm gap groups. Morphometrical analysis of the regenerated nerve were performed at the end of the follow-up. The group with an autograft achieved faster and higher levels of reinnervation for the four functions tested than any of the groups repaired by tubulization. The introduction of a small nerve transplant improved regeneration and reinnervation with respect to a saline solution filled tube slightly with a 4 mm gap, but significantly with a 6 mm long gap. The beneficial effects of the nerve transplant were significantly increased when it was predegenerated, while disappearing when its cellular component was eliminated by repeated freezing. The immunogenicity of the nerve transplant dramatically affected nerve regeneration, as it was impeded by an heterologous transplant in the tube. In summary, the use of silicone chambers with an autologous predegenerated nerve transplant may be an alternative for repairing long gaps in injured nerves, approaching the level of success of an ideal autologous nerve graft.