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

Periodontal defect regeneration in severe periodontitis relies on the differentiation and proliferation of periodontal ligament cells (PDLCs). Recently, an emerging 2D nanomaterial, MXene (Ti 3 C 2 T x ), 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 3 C 2 T x has exhibited satisfactory biocompatibility and induced distinguish osteogenic differentiation of human PDLCs (hPDLCs), with upregulated osteogenesis‐related genes. Ti 3 C 2 T x manages to activate the Wnt/ β ‐catenin signaling pathway by enhancing the Wnt‐Frizzled complex binding, thus stabilizing HIF‐1 α and altering metabolic reprogramming into glycolysis. In vivo, hPDLCs pretreated by Ti 3 C 2 T x display excellent performance in new bone formation and osteoclast inhibition with enhanced RUNX2, HIF‐1 α , 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 3 C 2 T x has highly efficient therapeutic effects in osteogenic differentiation and periodontal defect repairment.