Bioactivated Oxidized Polyvinyl Alcohol towards Next-Generation Nerve Conduits Development.

Elena Stocco,Monica Dettin,Grazia M L Messina,Andrea Porzionato,Veronica Macchi,Alessia Lamanna,Giovanna Iucci,Deborah Sandrin,Alessandro Auditore,Martina Marsotto,Silvia Barbon,Raffaele De Caro,Antonino Licciardello,Enrico De Rose,Annj Zamuner

doi:10.3390/polym13193372

Abstract

The limitations and difficulties that nerve autografts create in normal nerve function recovery after injury is driving research towards using smart materials for next generation nerve conduits (NCs) setup. Here, the new polymer partially oxidized polyvinyl alcohol (OxPVA) was assayed to verify its future potential as a bioactivated platform for advanced/effective NCs. OxPVA-patterned scaffolds (obtained by a 3D-printed mold) with/without biochemical cues (peptide IKVAV covalently bound (OxPVA-IKVAV) or self-assembling peptide EAK (sequence: AEAEAKAKAEAEAKAK), mechanically incorporated (OxPVA+EAK) versus non-bioactivated scaffold (peptide-free OxPVA (PF-OxPVA) supports, OxPVA without IKVAV and OxPVA without EAK control scaffolds) were compared for their biological effect on neuronal SH-SY5Y cells. After cell seeding, adhesion/proliferation, mediated by (a) precise control over scaffolds surface ultrastructure; (b) functionalization efficacy guaranteed by bioactive cues (IKVAV/EAK), was investigated by MTT assay at 3, 7, 14 and 21 days. As shown by the results, the patterned groove alone stimulates colonization by cells; however, differences were observed when comparing the scaffold types over time. In the long period (21 days), patterned OxPVA+EAK scaffolds distinguished in bioactivity, assuring a significantly higher total cell amount than the other groups. Experimental evidence suggests patterned OxPVA-EAK potential for NCs device fabrication.

Highlights

A high incidence of nerve injuries and the limitations of autologous nerve supplies for grafting and nerve transfer has created interest towards the development of vanguardengineered nerve conduits (NCs) based on smart polymers to promote nerve repair processes
We described for the first time the preparation and characterization of the new polymer oxidized polyvinyl alcohol (OxPVA), distinguishing it as an intriguing material for the fabrication of biocompatible synthetic scaffolds [5], including devices to support nerve regeneration [6,7,8]
The ultrastructure of the supports was investigated by scanning electron microscopy (SEM); canalicular rows ran in parallel along the scaffolds upper surface

Summary

Introduction

A high incidence of nerve injuries and the limitations of autologous nerve supplies for grafting and nerve transfer has created interest towards the development of vanguardengineered nerve conduits (NCs) based on smart polymers to promote nerve repair processes. Different from the first-generation devices, which were based on synthetic, nonresorbable hollow tubes (i.e., silicone- or polytetra-fluoroethylene-based) and requiring a second surgery for removal [1], the next-generation NCs, in addition to biodegradability (like the ones currently in use), should assure a controlled regeneration in axons path. To achieve this purpose, the incorporation of bioactive elements including growth factors, topographical cues and supportive cells, is the most promising strategy [2]. Despite encouraging pre-clinical study results showing OxPVA ability to sustain axonal regeneration, the great intrinsic potential of the polymer deserves to be explored, bearing in mind the need for optimization in conduit microenvironments [3]

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