Hybrid nanocomposite conduit based on oxidized polyvinyl alcohol and multiwalled carbon nanotubes: a new device supporting peripheral nerve regeneration in animal model of disease

Abstract

Severe peripheral nerve injuries represent a significant clinical problem, and intense efforts are dedicated toward the identification of the ‘ideal’ nerve conduit (NC). In this context, incorporating electrical cues within the device wall seems to be extremely appealing. Here, a new NC based on the new polymer oxidized polyvinyl alcohol (OxPVA) (oxidation degree 1%) + water-soluble multiwalled carbon nanotubes (MWCNT-S) (0.1wt% in OxPVA) was developed and characterized for ultrastructure and mechanical behavior. Subsequently, OxPVA+MWCNT-S NCs were implanted in animal model of disease (Sprague–Dawley rat; sciatic nerve, gap: 5mm) and compared with OxPVA and Reverse Autograft. Following sciatic functional index evaluation, implants-associated outcomes were verified on explants through histology, immunohistochemistry, immunofluorescence and morphometric studies on semithin sections, after 6weeks from surgery. According to preclinical study evidence, all the NCs supported nerve regeneration (S100/β-tubulin/neurofilaments) without severe inflammatory reaction (CD3/F4/80). Morphometric studies showed the highest cross-section area and fascicular area for Reverse Autograft followed by OxPVA+MWCNT-S and OxPVA. The epineurium thickness was the highest in Reverse Autograft followed by OxPVA and OxPVA+MWCNT-S. Myelinated axon density was highest for OxPVA+MWCNT-S, followed by OxPVA and Reverse Autograft; myelinated axons total number followed this descending order Reverse Autograft˃OxPVA+MWCNT-S˃OxPVA. Additionally, the g-ratio distribution highlighted a similar trend for OxPVA+MWCNT-S and Reverse Autograft with most nerve fibers within the 0.6–0.7 interval. Atrophy of the operated-limb gastrocnemius was comparable in the whole cohort. Interestingly, MWCNT-S incorporation in OxPVA showed to be an appealing strategy to improve the morpho-structural outcomes associated with these devices.