Graphdiyne-Ivy fiber neural scaffold promotes stem cell directed differentiation and neuronal maturation.

Conductive nerve scaffolds have emerged as a promising alternative to autologous grafts for promoting nerve regeneration. However, the optimization of scaffold materials and the elucidation of their regulatory mechanisms on neural stem cell (NSC) differentiation remain critical research priorities. Graphdiyne (GDY), a novel two-dimensional carbon allotrope, exhibits excellent electrical conductivity and favorable biocompatibility, yet its application in the neural field is still in its infancy. In this study, a structurally synergistic GDY/polycaprolactone (GDY/PCL) conductive composite scaffold-termed the GDY-Ivy Fiber Neural Scaffold-was fabricated using a combined electrospinning-freeze-drying strategy. This approach enabled efficient GDY loading while preserving its intrinsic properties. The resulting scaffold demonstrated superior electrical conductivity, mechanical strength, structural stability, and cytocompatibility. In vitro experiments further confirmed that the GDY-Ivy Fiber Scaffold significantly promoted NSC differentiation into neurons, inhibited glial activation, and enhanced synapse formation and the generation of functionally mature neurons. RNA-Seq analysis revealed that the scaffold orchestrated multiple key signaling pathways, including neurotrophic factor and Wnt-related pathways, thereby promoting NSC neuronal differentiation and functional maturation. In vivo experiments demonstrated that the GDY-Ivy Fiber Neural Scaffold enhances guidance for axonal oriented growth and Schwann cell activation, and promotes neovascularization, thereby improving the repair quality of peripheral nerve injury. Overall, the GDY-Ivy Fiber Neural Scaffold developed in this study establishes an optimized electrophysiological and structural microenvironment that promotes neuronal growth. These findings not only expand the application scope of carbon-based materials in neuroregenerative medicine but also offer novel design strategies for neural repair scaffolds.