Peripheral nerve injuries are serious conditions, and surgical treatment has critical limitations. Therefore, nerve guidance conduits (NGCs) are proposed as an alternative. In this study, multifunctional NGCs are fabricated for the regeneration of injured peripheral nerves. Graphene oxide (GO) and gelatin-methacrylate (GelMA) are polymerized and chemically reduced to form reduced (GO/GelMA) (r(GO/GelMA)). The prepared materials present good electrical conductivity, flexibility, mechanical stability, and permeability, which are suitable for use as NGCs. In vitro studies show 2.1-and 1.4-fold promotion of neuritogenesis of PC12 neuronal cells on r(GO/GelMA) compared to GelMA and unreduced GO/GelMA, respectively. Animal studies using a rat sciatic nerve injury model with a 10 mm gap between the proximal and distal regions of the defect reveal that r(GO/GelMA) NGCs significantly enhance peripheral nerve regeneration, indicated by improved muscle weight increase, electro-conduction velocity, and sciatic nerve function index. Specifically, r(GO/GelMA) NGCs are utilized to potentiate regrowth with myelination in rat sciatic nerves followed by histological, immunohistological, and morphometrical analyses. This study successfully shows the feasibility of electrically conductive hydrogel NGCs as functional conduits for improved nerve regeneration in a preclinical study, where these NGCs can not only mimic nerve tissues but also strongly promote nerve regeneration.

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In this study, we designed a cell-adhesive poly(ethylene glycol) (PEG)-based hydrogel that simultaneously provides topographical and electrical stimuli to C2C12 myoblasts. Specifically, PEG hydrogels with microgroove structures of 3 μm ridges and 3 μm grooves were prepared by micromolding; in situ polymerization of poly(3,4ethylenedioxythiophene) (PEDOT) was then performed within the micropatterned PEG hydrogels to create a microgrooved conductive hydrogel (CH/P). The CH/P had clear replica patterns of the silicone mold and a conductivity of 2.49 × 10 −3 S/cm, with greater than 85% water content. In addition, the CH exhibited Young's modulus (45.84 ± 7.12 kPa) similar to that of a muscle tissue. The surface of the CH/P was further modified via covalent bonding with celladhesive peptides to facilitate cell adhesion without affecting conductivity. An in vitro cell assay revealed that the CH/P was cytocompatible and enhanced the cell alignment and elongation of C2C12 myoblasts. The microgrooves and conductivity of the CH/P had the greatest positive effect on the myogenesis of C2C12 myoblasts compared to the other PEG hydrogel samples without conductivity or/and microgrooves, even in the absence of electrical stimulation. Electrical stimulation studies indicated that the combination of topographical and electrical cues maximized the differentiation of C2C12 myoblasts into myotubes, confirming the synergetic effect of incorporating microgroove surface features and a conductive PEDOT component into hydrogels.

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A nonbiofouling conductive polymer (i.e., polypyrrole [PPy]) bioelectrode was fabricated by grafting zwitterionic methacryloyloxyethyl phosphorylcholine polymer (MPC) using gamma radiation.