Multifunctional Manganese Oxide Nanocomposite Hydrogel With Synergistic Reactive Oxygen Species‐Scavenging, Oxygen‐Generating, Immunomodulatory, and Photothermal Antimicrobial Activities for Enhanced Diabetic Wound Healing

Abstract

ABSTRACT Diabetic wounds are characterized by a complex pathological microenvironment, marked by persistent hypoxia, excessive reactive oxygen species (ROS), chronic inflammation, and bacterial infection. To address this challenge, we developed a multifunctional composite hydrogel (CFP/PC@MnO2) for diabetic wound healing. It is formed by covalent crosslinking of carboxymethyl chitosan (CMCS), 4‐formylphenylboronic acid (4FPBA), and polyvinyl alcohol (PVA) via Schiff base and boronate ester bonds, followed by incorporation of phycocyanin‐modified MnO2 nanoparticles (PC@MnO2 NPs). The CFP/PC@MnO2 hydrogel exhibits favorable mechanical properties, local injectability, self‐healing capability, tissue adhesion, and the ability to form a protective wound barrier. Meanwhile, the CFP/PC@MnO2 hydrogel degrades rapidly under ROS, releasing PC@MnO2 to scavenge ROS and generate O2 in situ to alleviate hypoxia; the PC@MnO2 NPs further exhibit strong NIR‐triggered photothermal antibacterial activity. In vitro, this hydrogel exhibits excellent biocompatibility, effectively scavenges ROS, alleviates oxidative stress, and suppresses inflammation. In a full‐thickness wound model in diabetic rats, the CFP/PC@MnO2 hydrogel combined with photothermal therapy effectively eradicates bacteria, promotes M2 macrophage polarization to modulate the immune microenvironment, and enhances angiogenesis and collagen deposition, thereby accelerating wound healing. Overall, this multifunctional hydrogel integrates ROS scavenging, self‐sustained oxygenation, immunomodulation, and photothermal antibacterial action, offering a synergistic, innovative strategy for diabetic wound treatment.