Concentration-Dependent Effects of MXenes on Viability and Odontogenic Differentiation of Human Dental Pulp Stem Cells.

Background/Objectives: MXenes (transition metal carbides, nitrides, and carbonitrides) are promising 2D nanomaterials for biomedical applications due to their high conductivity, mechanical strength, and hydrophilicity. This study investigated the concentration-dependent effects of Ti3C2Tx MXenes on the viability, mineralization, and odontogenic differentiation of human dental pulp stem cells (DPSCs). Methods: Ti3C2Tx MXenes were synthesized and characterized by Scanning Electron Microscope with Energy Dispersive X-ray (SEM/EDX), Dynamic Light Scattering (DLS), zeta potential, UV-Vis, and conductivity analysis. DPSCs were characterized by their mesenchymal stem cell phenotype (CD73+, CD90+, CD105+, CD34-, CD45-). Cells were exposed to 10, 50, and 100 µg/mL MXenes. Cell viability was assessed by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay and apoptosis was evaluated using Annexin V-FITC staining. Mineralization was assessed by Alizarin Red S staining. Odontogenic differentiation was evaluated by qPCR for DSPP, RUNX2, and OCN. Results: Characterization confirmed successful MXene synthesis with a zeta potential of -22 mV and conductivity of 6110 S/cm. MXenes at 10 and 50 µg/mLmaintained viability above 100%, while 100 µg/mL reduced viability to 65.6% at day 14 (p < 0.01). Apoptosis rates at 10 and 50 µg/mL (5.1% and 6.8%) were not significantly different from the control (4.2%), whereas 100 µg/mL significantly increased apoptosis to 28.4% (p < 0.01). Mineralization was enhanced at 10 and 50 µg/mL (p < 0.05 and p < 0.01) but reduced at 100 µg/mL (p < 0.01). Gene expression of DSPP, RUNX2, and OCN was upregulated 2-3-fold at 10-50 µg/mL but suppressed at 100 µg/mL (p < 0.01). Conclusions: Ti3C2Tx MXenes exert concentration-dependent effects on DPSCs. Moderate concentrations (10-50 µg/mL) promote metabolic activity, mineralization, and odontogenic differentiation, while high concentrations (100 µg/mL) induce apoptosis and cytotoxicity. These findings support the therapeutic potential of MXenes in regenerative dentistry, provided that concentration thresholds are carefully controlled.