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However, developing substrates with the advanced surface functionality, conductivity, and biocompatibility required for practical application is still challenging. Here, Ti<jats:sub>3<\/jats:sub>C<jats:sub>2<\/jats:sub>T<jats:italic><jats:sub>x<\/jats:sub><\/jats:italic> MXene is introduced as a coating nanomaterial for aligned poly(<jats:sc>l<\/jats:sc>\u2010lactide) (PLLA) nanofibers (M\u2010ANF) to enhance NSC neurogenesis and simultaneously tailor the cell growth direction. Ti<jats:sub>3<\/jats:sub>C<jats:sub>2<\/jats:sub>T<jats:italic><jats:sub>x<\/jats:sub><\/jats:italic> 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<jats:sub>3<\/jats:sub>C<jats:sub>2<\/jats:sub>T<jats:italic><jats:sub>x<\/jats:sub><\/jats:italic> MXene coating significantly promotes NSC differentiation into both neurons and astrocytes. Interestingly, Ti<jats:sub>3<\/jats:sub>C<jats:sub>2<\/jats:sub>T<jats:italic><jats:sub>x<\/jats:sub><\/jats:italic> 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<jats:sub>3<\/jats:sub>C<jats:sub>2<\/jats:sub>T<jats:italic><jats:sub>x<\/jats:sub><\/jats:italic> MXene modulates the fate of NSCs. Notably, surface modification by Ti<jats:sub>3<\/jats:sub>C<jats:sub>2<\/jats:sub>T<jats:italic><jats:sub>x<\/jats:sub><\/jats:italic> MXene mitigates the in vivo foreign body response to implanted PLLA nanofibers. This study confirms that Ti<jats:sub>3<\/jats:sub>C<jats:sub>2<\/jats:sub>T<jats:italic><jats:sub>x<\/jats:sub><\/jats:italic> MXene provides multiple advantages for decorating the aligned PLLA nanofibers to cooperatively improve neural regeneration.<\/jats:p>","DOI":"10.1002\/adhm.202300731","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T12:10:58Z","timestamp":1687349458000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Surface Functional Modification by Ti<sub>3<\/sub>C<sub>2<\/sub>T<i><sub>x<\/sub><\/i> MXene on PLLA Nanofibers for Optimizing Neural Stem Cell Engineering"],"prefix":"10.1002","volume":"12","author":[{"given":"Yi\u2010Dan","family":"Zhu","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Sleep Disordered Breathing Department of Otolaryngology\u2010Head and Neck Surgery Otolaryngology Institute of Shanghai JiaoTong University Shanghai 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