Ultrathin 2D Titanium Carbide MXene (Ti<sub>3</sub> C<sub>2</sub> T<sub>x</sub> ) Nanoflakes Activate WNT/HIF-1α-Mediated Metabolism Reprogramming for Periodontal Regeneration.

Cui, Di; Kong, Na; Ding, Liang; Guo, Yachong; Yang, Wenrong; Yan, Fuhua · Adv Healthc Mater · 2021

basic_science · Level V

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Abstract

Periodontal defect regeneration in severe periodontitis relies on the differentiation and proliferation of periodontal ligament cells (PDLCs). Recently, an emerging 2D nanomaterial, MXene (Ti<sub>3</sub> C<sub>2</sub> T<sub>x</sub> ), has gained more and more attention due to the extensive antibacterial and anticancer activity, while its potential biomedical application on tissue regeneration remains unclear. Through a combination of experimental and multiscale simulation schemes, Ti<sub>3</sub> C<sub>2</sub> T<sub>x</sub> has exhibited satisfactory biocompatibility and induced distinguish osteogenic differentiation of human PDLCs (hPDLCs), with upregulated osteogenesis-related genes. Ti<sub>3</sub> C<sub>2</sub> T<sub>x</sub> manages to activate the Wnt/β-catenin signaling pathway by enhancing the Wnt-Frizzled complex binding, thus stabilizing HIF-1α and altering metabolic reprogramming into glycolysis. In vivo, hPDLCs pretreated by Ti<sub>3</sub> C<sub>2</sub> T<sub>x</sub> display excellent performance in new bone formation and osteoclast inhibition with enhanced RUNX2, HIF-1α, and β-catenin in an experimental rat model of periodontal fenestration defects, indicating that this material has high efficiency of periodontal regeneration promotion. It is demonstrated in this work that Ti<sub>3</sub> C<sub>2</sub> T<sub>x</sub> has highly efficient therapeutic effects in osteogenic differentiation and periodontal defect repairment.

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