MXene-Integrated Dual Network Hydrogel Accelerates Radiation-Combined Wound Healing through Modulating Oxidative Stress and Immune Response

Radiation-induced skin injury (RSI) remains a significant clinical challenge due to persistent oxidative stress, chronic inflammation, and impaired tissue regeneration. It is demonstrated that RSI is accompanied by dysregulation of the immune microenvironment, wherein macrophages act as key regulators of all pathological cascades. Here, we developed a dual network hydrogel (Gel/SA@MXene) through dual cross-linking via UV irradiation and calcium ions to accelerate radiation-combined wound healing. The hydrogel provided good biocompatibility, tunable mechanical properties, and controllable degradability by adjusting the composition ratio of GelMA and SA, cross-linking density, and the incorporation of MXene, where SA formed an extensive hydrogen-bonding network with MXene nanosheets to stabilize them and ensure homogeneous dispersion. The optimized hydrogel degraded and supplied MXene nanosheets, which successfully mitigated oxidative stress, promoted macrophage polarization toward the M2 phenotype, and broke the cycle of chronic inflammation. This remodeled immune microenvironment effectively alleviated oxidative damage in radiation-exposed HaCaT skin cells and supported cell migration and proliferation. In addition, <i>in vivo</i> experiments revealed that Gel/SA@MXene significantly ameliorated tissue inflammation and enhanced collagen deposition, thereby facilitating the healing of the skin wounds complicated by radiation injury Overall, this study highlights the potential of Gel/SA@MXene as a multifunctional platform that integrates antioxidant, immunomodulatory, and regenerative functions, effectively transforming the irradiated wound bed from a state of metabolic paralysis to one conducive to healing.