Surface Functional Modification by Ti3C2Tx MXene on PLLA Nanofibers for Optimizing Neural Stem Cell Engineering

Abstract

AbstractOptimizing 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, Ti3C2Tx 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. Ti3C2Tx 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, Ti3C2Tx MXene coating significantly promotes NSC differentiation into both neurons and astrocytes. Interestingly, Ti3C2Tx 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 Ti3C2Tx MXene modulates the fate of NSCs. Notably, surface modification by Ti3C2Tx MXene mitigates the in vivo foreign body response to implanted PLLA nanofibers. This study confirms that Ti3C2Tx MXene provides multiple advantages for decorating the aligned PLLA nanofibers to cooperatively improve neural regeneration.