Bilayer hydrogel with ROS-triggered release and thermal regulation ability for diabetic infected wounds healing

Abstract Persistent bacterial infection, oxidative stress imbalance, and cellular dysfunction within diabetic wound microenvironments represent key clinical challenges that hinder wound healing. To address these challenges, we developed a smart reactive oxygen species (ROS)-responsive bilayer thermoregulatory hydrogel, PP@PZC&SAg. The system was based on a dynamically cross-linked phenylboronate ester network. The in situ green synthesis of Ag nanoparticles endowed the hydrogel with highly efficient photothermal bactericidal capabilities, whereas the incorporated zinc/cerium layered double oxide nanozyme (PZC) mimicked catalase activity to scavenge excess ROS in the microenvironment. The top layer comprised a thermosensitive hydrogel that utilized its phase-change properties to precisely regulate photothermal temperatures, thereby effectively destroying bacterial biofilms while preventing thermal damage to surrounding tissues. The PP@PZC&SAg hydrogel system exhibited considerable photothermal activity, rapidly reaching and maintaining a stable operating temperature while simultaneously eliminating bacteria and disrupting biofilms. Furthermore, through synergistic ROS scavenging and the release of active Zn and Ce ions, this system restored endothelial cell proliferation, migration, and tubulogenic capacity, which are typically impaired under high-glucose conditions, ultimately promoting rapid diabetic wound healing. This approach simultaneously combats bacterial infections, alleviates oxidative stress, and restores cellular function, thereby offering a novel, multifaceted, and targeted therapeutic strategy for treating diabetic wounds.