Graphene-Metal Nanocomposites for Precise Electrical Modulation of Neural Stem Cells: Mechanisms and Therapeutic Potential

Spinal cord injury (SCI) remains one of the most formidable challenges in neurorestoratology, characterized by limited functional recovery due to an inhibitory microenvironment, glial scar formation, and loss of electrophysiological continuity. Although neural tissue engineering has emerged as a promising strategy for reconstructing disrupted neural circuits, conventional scaffolds often fail to deliver precise bioelectrical cues or effectively regulate neural stem cell (NSC) fate. In this review, we critically examine the synergistic potential of graphene-based nanocomposites doped with noble metals, particularly gold (Au) and silver (Ag), as advanced bioactive interfaces for SCI repair. Emphasis is placed on interfacial electrochemistry, where metal nanoparticles act as electronic bridges that enhance charge injection capacity, reduce interfacial impedance, and modulate capacitive coupling at the cell–material interface.We further analyze electro-mechanical mechanisms induced by electrical stimulation, including activation of voltage-gated calcium channels, Ca 2+ influx, and downstream PI3K/Akt/mTOR and β-catenin/Wnt signaling pathways governing neuronal differentiation, survival, neurite outgrowth, and electrophysiological maturation. Emerging evidence suggests that nanotopography and plasmonic features enhance axonal alignment, although their relative contributions remain unresolved.Despite translational challenges such as long-term stability, biodegradability, and the transition toward wireless stimulation, graphene–metal nanocomposites represent a next-generation class of active neural interfaces with strong potential for functional recovery following SCI.