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The repair of peripheral nerve traumatic lesions still represents a major cause of permanent motor and sensory impairment. In case of substance loss, a nerve guide should be used to bridge the proximal with the distal stump of the severed nerve. The effectiveness of hollow nerve guides is limited by the delay of axonal growth due to the absence of a regeneration substrate inside the conduit. To fasten up nerve regeneration, nerve guides should thus be enriched by a luminal filler. In this study, we investigated, in a 12-mm rat sciatic nerve defect experimental model, the effectiveness of chitosan-based conduits of different acetylation filled either with a hyaluronic acid gel (NVR gel) or with a magnetic fibrin hydrogel, in comparison with traditional autografts. Results showed that all types of artificial nerve conduits led to functional recovery not significantly different from autografts. By contrast, morphological and morphometrical analyses showed that the best results among nerve guides were found in medium degree of acetylation (DAII: ∼5%) chitosan conduits enriched with the NVR gel.

Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half‐life of few minutes. In previous studies, it was demonstrated that conjugation of various neurotrophic factors to iron oxide nanoparticles (IONP) led to stabilization of the growth factors and to the extension of their biological activity compared to the free factors. In vitro studies performed on organotypic dorsal root ganglion (DRG) cultures seeded in NVR gel (composed mainly of hyaluronic acid and laminin) revealed that the glial cell–derived neurotrophic factor (GDNF) conjugated to IONP‐enhanced early nerve fiber sprouting and accelerated the onset and progression of myelin significantly earlier than the free GDNF and other free and conjugated factors. The present article summarizes results of in vivo study, aimed to test the effect of free versus conjugated GDNF on regeneration of the rat sciatic nerve after a severe segment loss. We confirmed that nerve device enriched with a matrix with GDNF gives more successful results in term of regeneration and functional recovery in respect to the hollow tube; moreover, there are no detectable differences between free versus conjugated GDNF.