Bilayer nerve guidance conduits for continuous delivery of NGF@ZIF-8 nanoparticles for peripheral nerve injury repair

Peripheral nerve injury remains a major clinical challenge due to limited regenerative capacity and insufficient therapeutic strategies. In this study, we developed biomimetic nerve guidance conduits composed of high-concentration gelatin methacryloyl (GelMA) hydrogel (GMH), providing mechanical support and structural integrity. The conduits lumen was filled with a softer, low-concentration GelMA hydrogel (GML) incorporating zeolitic imidazolate framework-8 (ZIF-8) nanoparticles encapsulating nerve growth factor (NGF), enabling sustained neurotrophic delivery. This bilayer design combines mechanical reinforcement with localized biochemical stimulation. In vitro experiments demonstrate that the system can continuously release NGF, exhibits good cellular compatibility, promotes neurite outgrowth in PC-12 cells, and can facilitate the conversion of RAW264.7 cells to an anti-inflammatory phenotype. Rat sciatic nerve injury model experiments have demonstrated that these nerve guidance conduits have a beneficial effect on the regeneration and functional recovery of nerve axons. Together, these findings highlight a versatile platform for nerve guidance conduits with the potential to improve functional recovery in peripheral nerve regeneration.