Dual-Responsive Recombinant Human Collagen Hydrogel Delivering Manganese-Based Nanozymes for Temporally Synergistic Repair of Oxidative Stress Wounds

Abstract The clinical treatment of oxidative stress wounds remains challenging, as existing dressings often fail to simultaneously achieve timely clearance of microenvironmental reactive oxygen species (ROS) and effective reconstruction of the extracellular matrix. In this study, we constructed a dual-network hydrogel (denoted as Gel/MnBTC) composed of methacrylated recombinant human type III collagen (rhCol III-MA) and phenylboronic acid-grafted hyaluronic acid (HA-PBA), encapsulating polydopamine-coated manganese-based metal−organic framework nanozymes (MnBTC@PDA) within the matrix. Photoinduced free-radical polymerization synergized with dynamic boronate ester bonds to form a stable yet responsively dissociable matrix. Under acidic and high-ROS microenvironments, the system released nanozymes on demand, rapidly scavenging ROS via superoxide dismutase (SOD)-like and catalase (CAT)-like activities, thereby relieving oxidative inhibition of fibroblasts and restoring their migratory capacity. In the later stages, the collagen backbone significantly promoted re-epithelialization and the mature deposition of type I collagen. In vivo experiments demonstrated that Gel/MnBTC accelerated wound closure, remodeled the immune microenvironment, and exhibited favorable biocompatibility and temporally synergistic repair efficacy. These properties render Gel/MnBTC a promising smart-responsive dressing for the treatment of oxidative stress wounds.