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

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@MnO 2 ) 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 MnO 2 nanoparticles (PC@MnO 2 NPs). The CFP/PC@MnO 2 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@MnO 2 hydrogel degrades rapidly under ROS, releasing PC@MnO 2 to scavenge ROS and generate O 2 in situ to alleviate hypoxia; the PC@MnO 2 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@MnO 2 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.

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Publication Details

Journal
Advanced Science
Published
2026-07-24
DOI
https://doi.org/10.1002/advs.76774
Primary Topic
Wound Healing and Treatments
Type
article
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article

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

Yixiang Hepeng, Ruiyuan Liu, Jingxian Wu, Zhi Xu et al.
Advanced Science
Wound Healing and Treatments
article

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

Yixiang Hepeng, Ruiyuan Liu, Jingxian Wu, Zhi Xu, Xu Wu, Z L Yang, Bosong Zhou, X Luo, Chaoyang Huang, Xiang Li
article en

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@MnO 2 ) 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 MnO 2 nanoparticles (PC@MnO 2 NPs). The CFP/PC@MnO 2 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@MnO 2 hydrogel degrades rapidly under ROS, releasing PC@MnO 2 to scavenge ROS and generate O 2 in situ to alleviate hypoxia; the PC@MnO 2 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@MnO 2 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.

Advanced Science
Kunming Medical University (CN), Nanfang Hospital (CN), Southern Medical University (CN)
Openalex Percentile: Top 12%
Wound Healing and Treatments
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