Sprayable MXene Hydrogels With Composition‐Driven Interfacial Stabilization and on‐Skin Gelation for Conformal Postsurgical Photothermal Therapy

ABSTRACT Oxidative degradation of Ti 3 C 2 T x MXene in aqueous and biological environments remains a persistent obstacle to its long‐term use in biomedical applications, yet the role of the surrounding polymer matrix in governing this process has received little systematic attention. Here, we show that the lactide‐to‐glycolide ratio of a PLGA‐PEG‐PLGA triblock copolymer directly controls interfacial interactions at the MXene surface and, through this mechanism, determines how well the encapsulated nanosheets resist oxidation over time. Combined computational and experimental analyses reveal that glycolide‐rich segments form dense hydrogen‐bonding networks at the MXene interface, providing effective surface protection despite accelerated bulk hydrolysis. This competing interplay defines a compositional window in which MXene stability and hydrogel degradability are simultaneously optimized, a balance we validate through combined DFT, molecular dynamics, and experimental characterization. Building on this design principle, we formulate a sprayable composite that gels in situ upon contact with tissue, conformally coating irregular wound surfaces without manual placement. The optimized hydrogel exhibits robust photothermal performance under physiological conditions and effectively suppresses tumor growth in a postoperative melanoma model. These findings highlight the importance of interfacial design in stabilizing oxidation‐sensitive nanomaterials within dynamic polymer systems and provide practical guidelines for developing durable MXene‐based biomedical platforms.