Stability and dermal safety of Ti₃C₂T_x MXenes for potential skin-interfaced biosensor applications

Ti₃C₂T_x MXene is a two-dimensional material with exceptional electrical conductivity, rendering them promising candidates as ink for printable skin biosensors. However, their susceptibility to oxidation under biologically relevant conditions and the consequences of oxidation on material properties remain unclear, posing challenges for practical applications. The skin is the barrier to the external environment. Its microenvironment, including sweat, may influence MXenes stability and behavior. Rigorous dermal safety assessment is therefore essential before MXenes widespread use. In this study, we systematically investigated the oxidation kinetics of Ti₃C₂T_x MXenes with different flake sizes in biologically relevant solutions under varying temperatures and light exposure. Our results showed that oxidation was accelerated primarily by ionic strength and temperature. To prolong the lifetime of MXenes, we evaluated common antioxidant skincare ingredients vitamin E, niacinamide, and N-acetyl cysteine, finding that vitamin E significantly slowed oxidation in dispersions. To assess oxidation-dependent toxicity, we examined skin irritation and sensitization induced by freshly synthesized, partially oxidized, and fully oxidized MXenes. Accordingly, MXene dispersions were pre-incubated to obtain partially and fully oxidized samples. Oxidation was defined by the loss of the plasmonic band in the UV-Vis spectrum, a functional readout linked to conductivity, and thus relevant to the intended application of MXenes. Then, dermal toxicity was assessed using the KeratinoSens® assay and reconstituted human scaffold-free skin cultures. Across all oxidation states, Ti₃C₂T_x MXenes did not induce statistically significant skin irritation or sensitization. Furthermore, cellular uptake and mechanistic insights were explored by using confocal Raman spectroscopy and flow cytometry, showing Ti₃C₂T_x MXene internalization and reduction in intracellular reactive oxygen species level. Together, these findings reveal the oxidation behavior of Ti₃C₂T_x MXenes, identify a practical strategy to extend their functional lifetime, and establish dermal safety profiles under potential application relevant conditions, providing key intermediate evidence for future safe and sustainable biomedical applications.