Vertical Nanowire Electrode Array for Enhanced Neurogenesis of Human Neural Stem Cells via Intracellular Electrical Stimulation

Extracellular electrical stimulation (ES) can provide electrical potential from outside the cell membrane, but it is often ineffective due to interference from external factors such as culture medium resistance and membrane capacitance. To address this, we developed a vertical nanowire electrode array (VNEA) to directly provide intracellular electrical potential and current to cells through nanoelectrodes. Using this approach, the cell membrane resistivity and capacitance could be excluded, allowing effective ES. Human fetal neural stem cells (hfNSCs) were cultured on the VNEA for intracellular ES. Combining the structural properties of VNEA and VNEA-mediated ES, transient nanoscale perforation of the electrode was induced, promoting cell penetration and delivering current to the cell. Intracellular ES using VNEA improved the neuronal differentiation of hfNSCs more effectively than extracellular ES and facilitated electrophysiological functional maturation of hfNSCs because of the enhanced voltage-dependent ion-channel activity. The results demonstrate that VNEA with advanced nanoelectrodes serves as a highly effective culture and stimulation platform for stem-cell neurogenesis.