Toward Safer Biomedical Applications of MXenes: How Etching and Delamination Influence the Biocompatibility of Ti-Based MXenes

Engineering Biocompatible MXenes: Influence of Etching and Delamination Routes on Titanium-Based MXenes for Biomedical Applications.

The growing interest in MXenes for biomedical use stems from their conductivity, photothermal response, and versatile surface chemistry. However, their biological compatibility remains highly sensitive to synthesis parameters. Here, we systematically evaluated how etching conditions (concentrated vs. diluted HF/HCl) and intercalation methods (Li⁺ vs. Na⁺) influence the physicochemical properties and biocompatibility of Ti₃C₂Tₓ and Ti₃C₁.₅N₀.₅Tₓ.

Surface analyses showed that dilute etchants combined with Na⁺ intercalation increased hydroxylation and reduced fluorine surface terminations. In vitro assays with human keratinocytes revealed that Ti₃C₁.₅N₀.₅Tₓ consistently outperformed Ti₃C₂Tₓ, with decreased cytotoxicity, lower ROS production, reduced inflammatory cytokine release, and preserved wound-healing function. Among Ti₃C₂Tₓ variants, diluted etching conditions markedly improved biological outcomes.

At physiologically relevant doses, optimized MXenes supported keratinocyte viability, accelerated wound closure, and minimized apoptosis, oxidative stress, and inflammatory signaling. Complementary in vivo histological evaluations confirmed negligible skin toxicity, with no tissue damage or immune infiltration observed. These findings demonstrate that subtle adjustments to etching and delamination protocols can finely tune MXene surface chemistry and substantially enhance biocompatibility. Such insights offer a practical roadmap for developing safer MXenes in biomedical applications.