2D Ti₃C₂T_xMXene couples electrical stimulation to promote proliferation and neural differentiation of neural stem cells

Preclinical studies involving stem cells require efficient physiochemical regulations on the fate of such cells. Because of their unique planar structure, metallic conductivity, and flexible surface functionalization, MXenes show potential for modulating stem cell fate. Here, the Ti₃C₂T_xMXenenanosheets are dispersed on tissue culture polystyrene (TCPS). When primary mouse neural stem cells (NSCs) are cultured on laminin-coated Ti₃C₂T_xMXene film, they form stable adhesion, retain their proliferative ability, and show extensive spreading of terminal extensions. With respect to their functional activity, NSCs cultured on Ti₃C₂T_xMXene films form more active and synchronous network activity than those cultured on TCPS substrates. Moreover, Ti₃C₂T_xMXene film significantly promotes the neural differentiation and the neurons have longer neurites and greater numbers of branch points and branch tips. NSC-derived neurons grown on the Ti₃C₂T_x MXene film preserved normal synapse development. Finally, electrical stimulation coupled with Ti₃C₂T_xMXene film significantly enhances the proliferation of NSCs. These results indicate that Ti₃C₂T_xMXene is an efficient interface for the proliferation and neural differentiation of NSC and the maturation of NSC-derived neurons, which expands the potential uses of the MXene family of materials and provides new strategies for stem cell studies. Statement of significance: The 2DTi₃C₂T_xMXenenanosheets were applied to be an interface for regulating neural stem cells (NSCs). NSCs cultured on Ti₃C₂T_xMXene film possessed higher proliferative ability with higher and more synchronous electrical activities. Moreover, Ti₃C₂T_xMXene film significantly promoted the neural differentiation ratio of NSCs, and the neurons derived from NSCs cultured on Ti₃C₂T_xMXene film had longer neurites and greater numbers of branch points and branch tips.When electrical stimulation was applied to NSCs via the Ti₃C₂T_xMXene film, it significantly enhanced the proliferation of NSCs. This work expands the potential uses of the MXene family of materials and provides new strategies for stem cell studies.