A temporally coordinated MXene@PDA hydrogel sequentially orchestrates hemostasis, inflammation resolution, and...

Uncontrolled hemorrhage and oxidative stress-driven inflammation following acute trauma remain major clinical challenges. Here, we report an ultrafast self-gelling biomimetic hydrogel (PSMP) that integrates an MXene@polydopamine (MXene@PDA) heterojunction nanozyme into a dynamic polyvinyl alcohol/silk fibroin matrix. PSMP provides rapid wet-tissue adhesion and mechanical sealing, thereby enabling efficient hemostasis in complex bleeding environments. The dynamic polymer network, together with catechol-mediated interfacial interactions and the hemostasis-promoting effect of MXene@PDA, allows PSMP to rapidly fill bleeding cavities, firmly adhere to wet tissues, and accelerate clot formation. During the transition to tissue repair, reactive oxygen species (ROS)-responsive matrix degradation triggers the release of MXene@PDA nanozymes. These nanozymes scavenge mitochondrial ROS, preserve mitochondrial homeostasis, and are associated with reduced activation of cGAS-STING-NF-κB-related inflammatory signaling. In parallel, PSMP promotes pro-angiogenic responses consistent with activation-associated changes in the Angiopoietin-Tie2 signaling pathway. Evaluations in rodent, rabbit, and porcine models of lethal hemorrhage and full-thickness wounds support an association between PSMP treatment and the temporal coordination of early hemostasis, subsequent inflammation attenuation, and angiogenic responses. This temporally coordinated system offers a promising strategy for advanced wound management.