Surface Functional Modification by Ti ₃C ₂T _x MXene on PLLA Nanofibers for Optimizing Neural Stem Cell Engineering

Abstract

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, Ti ₃C ₂T _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. Ti ₃C ₂T _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, Ti ₃C ₂T _x MXene coating significantly promotes NSC differentiation into both neurons and astrocytes. Interestingly, Ti ₃C ₂T _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 Ti ₃C ₂T _x MXene modulates the fate of NSCs. Notably, surface modification by Ti ₃C ₂T _x MXene mitigates the in vivo foreign body response to implanted PLLA nanofibers. This study confirms that Ti ₃C ₂T _x MXene provides multiple advantages for decorating the aligned PLLA nanofibers to cooperatively improve neural regeneration.