2D TiCTMXene 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 TiCTMXenenanosheets are dispersed on tissue culture polystyrene (TCPS). When primary mouse neural stem cells (NSCs) are cultured on laminin-coated TiCTMXene 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 TiCTMXene films form more active and synchronous network activity than those cultured on TCPS substrates. Moreover, TiCTMXene 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 TiCT MXene film preserved normal synapse development. Finally, electrical stimulation coupled with TiCTMXene film significantly enhances the proliferation of NSCs. These results indicate that TiCTMXene 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 2DTiCTMXenenanosheets were applied to be an interface for regulating neural stem cells (NSCs). NSCs cultured on TiCTMXene film possessed higher proliferative ability with higher and more synchronous electrical activities. Moreover, TiCTMXene film significantly promoted the neural differentiation ratio of NSCs, and the neurons derived from NSCs cultured on TiCTMXene film had longer neurites and greater numbers of branch points and branch tips.When electrical stimulation was applied to NSCs via the TiCTMXene 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.