Triple-Cue-Guided Multichannel Hydrogel Conduit to Synergistically Enhance Peripheral Nerve Repair

Multichannel nerve guidance conduits (NGCs) have demonstrated superior efficacy in the regeneration of large nerve defects. Here, we present the incorporation of three synergistic guiding cues into a single multichannel hydrogel conduit: topographical guidance, a conductivity gradient, and a nerve growth factor (NGF) gradient. The aligned hydrogel conduit is fabricated through directional lyophilization of a graphene oxide (GO)/poly(vinyl alcohol) (PVA) solution. The conductivity gradient is achieved via the dopamine-induced reduction of GO, during which amino groups with a concentration gradient are simultaneously generated, facilitating the eventual formation of an NGF gradient. <i>In vitro</i> experiments validate the excellent guidance effect and promotion of neuritogenesis by the NGF-gradient/aligned PVA/reduced graphene oxide (rGO)/polydopamine (PDA)/heparin hydrogel conduit (denoted as NGF-AGHC) on PC12 neuronal cells. Furthermore, <i>in vivo</i> testing reveals that NGF-AGHC exhibits a stronger longitudinal attraction to axons and promotes remyelination. Additionally, functional recovery assessments, histological analyses, and morphological evaluations all indicate that NGF-AGHC significantly enhances peripheral nerve regeneration, with performance comparable to that of the autograft group. Altogether, through a straightforward preparation method integrating topographical guidance, conductivity gradients, and NGF gradients, our NGCs offer a promising approach to peripheral nerve repair.