Evaluation of biodegradable polymer conduits--poly(L-lactic acid)--for guiding sciatic nerve regeneration in mice.

Polymeric biomaterials are often used for stimulating nerve regeneration. Among different conduits, poly(lactide acid) - PLA polymer is considered to be a good substrate due to its biocompatibility and resorbable characteristics. This polymer is an aliphatic polyester which has been mostly used in biomedical application. It is an organic compound with low allergenic potential, low toxicity, high biocompatibility and predictable kinetics of degradation. In this study we fabricated and evaluated a PLA microporous hollow fiber as a conduit for its ability to bridge a nerve gap in a mouse sciatic nerve injury model. The PLA conduit was prepared from a polymer solution, throughout extrusion technique. The left sciatic nerve of C57BL/6 mouse was transected and the nerve stumps were placed into a resorbable PLA (PLA group) or a PCL conduit (PCL group), n=5 each group. We have also used another group in which the nerves were repaired by autograft (autograft group, n=5). Motor function was analyzed according to sciatic functional index (SFI). After 56days, the regenerated nerves were processed for light and electron microscopy and morphometric analyses were performed. A quantitative analysis of regenerated nerves showed significant increase in the number of myelinated fibers and blood vessels in animals that received PLA conduit. The PLA group exhibited better overall tissue organization compared to other groups. Presenting well-organized bundles, many regenerating clusters composed of preserved nerve fibers surrounded by layers of compacted perineurium-like cells. Also the SFI revealed a significant improvement in functional recovery. This work suggests that PLA conduits are suitable substrate for cell survival and it provides an effective strategy to be used to support axonal growth becoming a potential alternative to autograft.

Mesenchymal stem cells in a polycaprolactone conduit promote sciatic nerve regeneration and sensory neuron survival after nerve injury.

Despite the fact that the peripheral nervous system is able to regenerate after traumatic injury, the functional outcomes following damage are limited and poor. Bone marrow mesenchymal stem cells (MSCs) are multipotent cells that have been used in studies of peripheral nerve regeneration and have yielded promising results. The aim of this study was to evaluate sciatic nerve regeneration and neuronal survival in mice after nerve transection followed by MSC treatment into a polycaprolactone (PCL) nerve guide. The left sciatic nerve of C57BL/6 mice was transected and the nerve stumps were placed into a biodegradable PCL tube leaving a 3-mm gap between them; the tube was filled with MSCs obtained from GFP+ animals (MSC-treated group) or with a culture medium (Dulbecco's modified Eagle's medium group). Motor function was analyzed according to the sciatic functional index (SFI). After 6 weeks, animals were euthanized, and the regenerated sciatic nerve, the dorsal root ganglion (DRG), the spinal cord, and the gastrocnemius muscle were collected and processed for light and electron microscopy. A quantitative analysis of regenerated nerves showed a significant increase in the number of myelinated fibers in the group that received, within the nerve guide, stem cells. The number of neurons in the DRG was significantly higher in the MSC-treated group, while there was no difference in the number of motor neurons in the spinal cord. We also found higher values of trophic factors expression in MSC-treated groups, especially a nerve growth factor. The SFI revealed a significant improvement in the MSC-treated group. The gastrocnemius muscle showed an increase in weight and in the levels of creatine phosphokinase enzyme, suggesting an improvement of reinnervation and activity in animals that received MSCs. Immunohistochemistry documented that some GFP+ -transplanted cells assumed a Schwann-cell-like phenotype, as evidenced by their expression of the S-100 protein, a Schwann cell marker. Our findings suggest that using a PCL tube filled with MSCs is a good strategy to improve nerve regeneration after a nerve transection in mice.