Peripheral nerve injury with substance loss: fabrication and in vivo evaluation of new bioactive devices

Severe peripheral nerve injuries (PNI) are a challenge in clinical practice as no commercial device guarantees outcomes better than those provided by autografts. In this context, there has been intense research devoted to improving nerve conduits (NC) and introducing bioactive molecules (self-assembling peptides, growth factors) seems to be a promising strategy. In this study, biofunctionalized NCs based on the new polymer oxidized polyvinyl alcohol (OxPVA) were developed and then implanted in a rat model of sciatic nerve transection (Sprague Dawley rat; gap: 5mm). Five experimental groups (Reverse Autograft, OxPVA, OxPVA+EAK, OxPVA+EAK-YIGSR, OxPVA+NGF) were considered and NC effectiveness was verified after 6 weeks by functional evaluations (sciatic functional index, gait analysis), histological (Hematoxylin-Eosin, Azan-Mallory, Toluidine-blue staining)/immunohistochemical (CD3, F4/80)/immunofluorescence (S100, PGP9.5) analyses and morphometric studies. The operated limb gastrocnemius muscle was also considered for eventual atrophy and fibroconnective infiltrate. In parallel, a pilot study on conduits fillers (EAK-YIGSR, hyaluronic acid, chitosan, and their EAK-YIGSR modification) was also conducted, aiming to evaluate their ultrastructural properties. The results confirmed the incorporation of EAK-YIGSR within the OxPVA as promising strategy to improve the outcomes associated with such devices; moreover, EAK-YIGSR displays a good potential as luminal filler for future pre-clinical studies in disease’s animal models.