Abstract

Muscle-in-vein conduit is successfully employed for repairing nerve injuries: the vein prevents muscle fiber dispersion, while the muscle prevents the vein collapse and creates a favorable environment for Schwann cell migration and axon regrowth. However, it requires microsurgical skills. In this study we show a simple strategy to improve the performance of a chitosan hollow tube by the introduction of fresh skeletal muscle fibers. The hypothesis is to overcome the technical issue of the muscle-in-vein preparation and to take advantage of fiber muscle properties to create an easy and effective conduit for nerve regeneration. Rat median nerve gaps were repaired with chitosan tubes filled with skeletal muscle fibers (muscle-in-tube graft), hollow chitosan tubes, or autologous nerve grafts. Our results demonstrate that the fresh skeletal muscle inside the conduit is an endogenous source of soluble Neuregulin 1, a key factor for Schwann cell survival and dedifferentiation, absent in the hollow tube during the early phase of regeneration. However, nerve regeneration assessed at late time point was similar to that obtained with the hollow tube. To conclude, the muscle-in-tube graft is surgically easy to perform and we suggest that it might be a promising strategy to repair longer nerve gap or for secondary nerve repair, situations in which Schwann cell atrophy is a limiting factor for recovery.

Highlights

  • The gold standard technique used to repair large peripheral nerve defects is the autologous nerve graft

  • In vitro experiments performed in this study demonstrated that (i) skeletal muscle fibers upregulate the expression of soluble Neuregulin 1 (NRG1) mRNA while they are degenerating and that (ii) the soluble NRG1 protein produced by the muscle is released in the medium

  • Our results show that the muscle-in-tube graft promotes nerve regeneration as efficiently as the hollow chitosan tube and that the fresh skeletal muscle inserted inside the chitosan conduit may be an endogenous source of soluble NRG1, a source that is absent in the hollow tube

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Summary

Introduction

The gold standard technique used to repair large peripheral nerve defects is the autologous nerve graft This procedure has some well-known disadvantages: the need of an additional surgery to harvest the donor nerve, sensory deficits at the donor site, the possibility of neuromain-continuity formation with consequent neuropathic pain, and the limited availability of donor nerves in terms of number and diameter [1,2,3]. Tubular conduits have proven to be an excellent alternative to autologous nerve grafts because they act as physical guidance for the regenerating axons and provide a protective environment for axonal growth by limiting surrounding tissue invasion and by reducing neuroma and scar tissue formation [5]. They facilitate the accumulation and the concentration of neurotrophic and neurotropic factors produced by the injured nerve stumps [6, 7]

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