Self-snapping hydrogel-based electroactive microchannels as nerve guidance conduits

Peripheral nerve regeneration with large defects needs innovative design of nerve guidance conduits (NGCs) which possess anisotropic guidance, electrical induction and right mechanical properties in one. Herein, we present, for the first time, facile fabrication and efficient neural differentiation guidance of anisotropic, conductive, self-snapping, hydrogel-based NGCs. The hydrogels were fabricated via crosslinking of graphitic carbon nitride (g-C(3)N(4)) upon exposure with blue light, incorporated with graphene oxide (GO). Incorporation of GO and in situ reduction greatly enhanced surface charges, while decayed light penetration endowed the hydrogel with an intriguing self-snapping feature by the virtue of a crosslinking gradient. The hydrogels were in the optimal mechanical stiffness range for peripheral nerve regeneration and supported normal viability and proliferation of neural cells. The PC12 ​cells differentiated on the electroactive g-C(3)N(4) H/rGO3 (3 ​mg/mL GO loading) hydrogel presented 47% longer neurite length than that of the pristine g-C(3)N(4) H hydrogel. Furthermore, the NGC with aligned microchannels was successfully fabricated using sacrificial melt electrowriting (MEW) moulding, the anisotropic microchannels of the 10 ​μm width showed optimal neurite guidance. Such anisotropic, electroactive, self-snapping NGCs may possess great potential for repairing peripheral nerve injuries.