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MXenes, two-dimensional transition metal carbides and nitrides, are increasingly explored for biomedical applications such as sensors, wound healing materials, and drug delivery systems.
Their biocompatibility, however, is strongly dependent on synthesis conditions. In this study, we examined the effects of etching and delamination strategies—using concentrated or diluted HF/HCl etchants and Li⁺ versus Na⁺ intercalation—on the surface chemistry and biological performance of Ti₃C₂Tₓ and its carbonitride analog Ti₃C₁.₅N₀.₅Tₓ.
Physicochemical analyses revealed that water-assisted etching and Na⁺ intercalation enhanced hydroxylation and reduced fluorine terminations. Biological assays with human keratinocytes (HaCaT) demonstrated superior performance of Ti₃C₁.₅N₀.₅Tₓ, which showed lower cytotoxicity, reduced ROS generation, minimal pro-inflammatory signaling, and preserved wound healing activity. For Ti₃C₂Tₓ, dilute etchants combined with Na⁺ intercalation significantly improved tolerance, lowering apoptosis and oxidative stress.
At subcytotoxic concentrations (≤25 μg/mL), optimized MXene formulations maintained cell viability, supported wound closure, and elicited minimal inflammatory responses. In vivo tests further confirmed the absence of acute skin toxicity or immune activation. Together, these results highlight the decisive role of surface terminations and intercalants in MXene–cell interactions and provide guidelines for engineering biocompatible MXenes suitable for biomedical translation.