Surface Functional Modification by Ti₃ C₂ T_x MXene on PLLA Nanofibers for Optimizing Neural Stem Cell Engineering

Optimizing cell substrates by surface modification of neural stem cells (NSCs), for efficient and oriented neurogenesis, represents a promising strategy for treating neurological diseases. However, developing substrates with the advanced surface functionality, conductivity, and biocompatibility required for practical application is still challenging. Here, Ti₃ C₂ T_x MXene is introduced as a coating nanomaterial for aligned poly(l-lactide) (PLLA) nanofibers (M-ANF) to enhance NSC neurogenesis and simultaneously tailor the cell growth direction. Ti₃ C₂ T_x MXene treatment provides a superior conductivity substrate with a surface rich in functional groups, hydrophilicity, and roughness, which can provide biochemical and physical cues to support NSC adhesion and proliferation. Moreover, Ti₃ C₂ T_x MXene coating significantly promotes NSC differentiation into both neurons and astrocytes. Interestingly, Ti₃ C₂ T_x MXene acts synergistically with the alignment of nanofibers to promote the growth of neurites, indicating enhanced maturation of these neurons. RNA sequencing analysis further reveals the molecular mechanism by which Ti₃ C₂ T_x MXene modulates the fate of NSCs. Notably, surface modification by Ti₃ C₂ T_x MXene mitigates the in vivo foreign body response to implanted PLLA nanofibers. This study confirms that Ti₃ C₂ T_x MXene provides multiple advantages for decorating the aligned PLLA nanofibers to cooperatively improve neural regeneration.