Artificial nerve guidance conduits (NGCs) have gained significant attention in the field of peripheral nerve regeneration for the treatment of critically sized nerve defects. Nanotechnology-based NGCs are being explored as potential solutions for repairing and reconstructing peripheral nerve injuries due to their unique structure and topography. In this study, we present a novel core–sheath GelMA/PCL nanofiber construct fabricated through electrospinning and phase separation methods. The core–sheath GelMA/PCL nanofibers replicate the topological morphology of the native extracellular matrix (ECM). The outer layer, composed of GelMA, serves as an “adhesion domain” facilitating direct interaction with surrounding cells and tissues while improving wettability, integrin-mediated cell adhesion/attachment, and degradation. PCL, acting as the “elastic domain” within the nanofibers, enhances mechanical properties, maintains long-term stability of the NGCs, and enables controlled release of GelMA. Histomorphometric analysis along with electrophysiological and behavioral assessments demonstrate that these core–sheath GelMA/PCL nanofiber-based NGCs can activate endogenous mechanisms for peripheral nerve repair while promoting sensory/motor nerve regeneration and functional recovery. Overall, our findings demonstrate that GelMA/PCL nanofibers within the nuclear sheath can effectively remodel the nerve regeneration microenvironment by integrating “mechanical- biochemical” signals, thereby offering a novel strategy for addressing critical-size nerve defects.

This study developed electroconductive GelMA/PCL/graphene oxide (GO) nanofibrous scaffolds and performed a preliminary in vitro evaluation for peripheral nerve repair, focusing on optimizing the GO concentration. GO (0.1–1.0 wt%) was incorporated into GelMA/PCL via electrospinning. The 1.0 wt% GO scaffold exhibited reduced fiber diameters (200–300 nm) and enhanced electrical conductivity (8.4 × 10⁻⁴ mS/cm). All scaffolds were superhydrophilic (contact angle ≈ 0°). Tensile strength and fracture strain increased up to 0.5 wt% GO but decreased at 1.0 wt% GO to levels not significantly different from those of the control. PC12 cells demonstrated robust adhesion, proliferation, and viability on all scaffolds. Under electrical stimulation (100 mV/cm), the 1.0 wt% GO scaffold promoted qualitative axonal elongation and directional alignment compared with scaffolds lacking GO or subjected to no electrical stimulation. Scaffold-immobilized GO showed no cytotoxicity in CCK-8 assays, indicating a favorable preliminary safety profile. These results highlight the potential of GelMA/PCL/1.0 wt% GO scaffolds as a promising platform for advanced nerve guidance conduits; however, further validation using primary neurons and in vivo models is required.