Ultrathin 2D Titanium Carbide MXene (Ti₃C₂T_x) Nanoflakes Activate WNT/HIF‐1α‐Mediated Metabolism Reprogramming for Periodontal Regeneration

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 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-1𝜶 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-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 3 C 2 T x has highly efficient therapeutic effects in osteogenic differentiation and periodontal defect repairment.

Piezoresistive MXene/Silk fibroin nanocomposite hydrogel for accelerating bone regeneration by Re-establishing electrical microenvironment

“…In summary, the excellent bone repairing ability of the 0.4%MXene/RSF + ES group may be ascribed to two factors: (i) MXene is degraded to release Ti-based species since the exposure to water and oxygen, which may promote osteogenesis and neovascularization. Cui et al demonstrated that MXene have highly efficient therapeutic effects for osteogenic differentiation by activating the WNT/HIF-1α-mediated metabolism reprogramming [ 60 ]. Meanwhile, it was also reported that Ti-molecules couple with osteogenesis and angiogenesis processes by upmodulating the PI3K/AKT signaling pathway [ 61 ].…”

Ti3C2TxMXene Composite 3D Hydrogel Potentiates mTOR Signaling to Promote the Generation of Functional Hair Cells in Cochlea Organoids

“…Whereas Cui et al have demonstrated that Ti 3 C 2 T x MXene induces distinguish differentiation of human periodontal ligament cells by activating WNT/HIF1-𝛼 signaling pathway. [26] Through GO enrichment analysis on mRNA-seq data, we find cell response to interferon-𝛽 in top 10 GO terms has been significantly up-regulated. Interferon-𝛽 activity has been reported to be regulated by mTOR signaling.…”

“…Others stated that MXene concentrations are safe up to 180 μg mL −1 for human periodontal ligament cells and safety up to 500 μg mL −1 for HaCat cell line in 2D culture system. [26,45] Furthermore, Ti 3 C 2 Tx is a potential material for tissue restoration following tumor surgery due to its great selectivity against tumor cells compared to normal cells. [46] In addition, MXenes have an outstanding electrical conductivity of ≈15 100 S cm−1 for a 214 nm thick film, [22] making it promising to adjust the conductivity of Matrigel.…”

“…It has been previously reported that MXene promoted the differentiation of human periodontal ligament cells through activating WNT/HIF1-𝛼 signaling. [26] Recently, mTOR signaling has been discovered to participate in the differentiation and long-term survival of hair cells. [14,31] Here, we found some of the top 10 upregulated GO terms were related to mTOR signaling, particularly the cell response to interferon-beta (Figure 4f).…”

“…[25] Recently, Ti 3 C 2 T x MXene has been reported to activate WNT/HIF-1𝛼-Mediated metabolism and induce osteogenic differentiation of human periodontal ligament cells. [26] Hypoxia-inducible factors-1𝛼 (HIF-1𝛼) transcription is enhanced by mTOR activity, while the addition of mTOR inhibitor rapamycin can eliminate many of the effects mediated by the expression of HIF-1𝛼. [27] mTOR activity has been reported to participate in the maintenance and differentiation of stem cells, including neural stem cells, [28] hematopoietic stem cells, [29] and germ stem cells.…”