Jul 2026· Advancement of science· 0 citations· 68 references
Medicine
TL;DR
This multifunctional hydrogel integrates ROS scavenging, self‐sustained oxygenation, immunomodulation, and photothermal antibacterial action, offering a synergistic, innovative strategy for diabetic wound treatment.
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.
A multifunctional, mechanism-targeted strategy that provides a rational, disease-relevant approach for treating chronic diabetic wounds by dampening inflammatory signaling and protecting reparative cells is developed.
Yuefei Zhu, Na Yan, Yongqiang Xiao et al.· Small· 0 citations
Diabetic wounds pose considerable therapeutic challenges owing to impaired tissue regeneration and elevated risk of bacterial infection. This study developed a hydrogel-based microenvironment-responsive multifunctional composite system. This composite material comprises a pH/reactive oxygen species (ROS) dual-responsive hydrogel scaffold formed by dihydrocaffeic acid-grafted chitosan and phenylboronic acid-functionalized oxidized dextran hinges, encapsulating gallium ions and ROS-responsive curcumin micelles. Taking advantage of the acidic microenvironment (pH 4.5-6.5) and elevated ROS levels in diabetic wounds, the composites exhibit significant efficacy in inhibiting bacterial biofilm formation, scavenging excess ROS, alleviating inflammatory responses, significantly promoting angiogenesis and collagen deposition. This integrated strategy successfully addresses major challenges in diabetic wound treatment-namely, susceptibility to infection, persistent inflammation, elevated oxidative stress, and impaired angiogenesis by enabling synergistic regulation of antibacterial, anti-inflammatory, antioxidant, and pro-regenerative effects. This comprehensive strategy bridges antimicrobial defense and immune regulation in the context of comprehensive wound management, thereby providing a valuable reference for the development of effective clinical therapies for diabetic wounds.
Jige Yuan, Kun Qian, Qu Tang et al.· Journal of materials chemist...· 0 citations
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 Zn/Ce 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.
Songjie Li, Han Chen, Xin Dan et al.· Nano Reseach· 0 citations
The antibacterial experiments results show that the combination of antibacterial and anti-inflammation mediated by TAPP/Mn3O4@CS-GA hydrogel can accelerate infected wound healing.
Ningning Xu, Yu Liu, Shuling Yu et al.· International Journal of Bio...· 0 citations
Healing of diabetic wounds is severely hindered by a persistent vicious cycle of bacterial infection and metabolic disorders. Pathological microenvironments, characterized by high glucose levels and excessive reactive oxygen species (ROS), exacerbate chronic inflammation and impede the transition of macrophages toward a pro-healing phenotype. To address these challenges, we developed a multi-stimuli-responsive composite hydrogel platform (GHFA/Cu@TA) by integrating fulvic acid (FA) and copper-tannic acid nanozymes (Cu@TA NPs) into a dynamic covalent network composed of methacrylated gelatin (GelMA) and phenylboronic acid-modified hyaluronic acid (HA-PBA). This platform implements a self-feedback mechanism to restore metabolic homeostasis: glucose-triggered release of Cu@TA NPs effectively scavenges microenvironmental ROS to drive tissue microenvironment remodeling, thereby decelerating responsive hydrogel degradation upon homeostasis normalization to ensure synchronized on-demand drug delivery. Intelligently released FA promotes M2 macrophage polarization to reshape the immune microenvironment, while Cu@TA NPs achieve photothermal biofilm eradication under near-infrared (NIR) light. This "metabolic sensing-feedback regulation-homeostasis reconstruction" strategy offers a distinct therapeutic framework for addressing diabetic wound and contributes to the rational design of bioactive dressings with stimuli responsiveness.
Na Yang, Lingling Tang, Huanghe Zeng et al.· International Journal of Bio...· 0 citations
Infected burn wounds are characterized by bacterial invasion, oxidative stress, and persistent inflammation, which severely impair tissue regeneration. Herein, we report a crosslinker-free, hydrogen-bonded cationic guar gum hydrogel (CBBM) co-loaded with berberine (BBR) and MnO2-coated black phosphorus nanosheets (BPNS@MnO2) for the microenvironment-adaptive treatment of infected burn wounds. The dynamic guar gum network endowed the hydrogel with injectability, self-healing ability, and conformal adaptability. BPNS@MnO2 exhibited pH-dependent enzyme-like activities, including OXD-like antibacterial activity under acidic conditions and SOD-/CAT-like ROS-scavenging activity under near-neutral conditions and endowed the hydrogel with NIR-triggered photothermal responsiveness. Moreover, NIR irradiation further enhanced the antibacterial efficacy and moderately enhanced BBR release from the hydrogel. In vitro, CBBM combined with NIR irradiation achieved potent antibacterial efficacy against S. aureus and E. coli under the tested conditions and reduced intracellular ROS levels. In vivo, the CBBM + NIR treatment accelerated infected burn wound healing, achieving a wound closure rate of 97.53 ± 2.01% by day 14, accompanied by reduced inflammation, enhanced collagen deposition, and increased expression of the angiogenesis-related markers VEGF and CD31. These results demonstrate that the CBBM hydrogel is a promising multifunctional guar gum-based dressing for infected burn wound healing by integrating local drug delivery, catalytic regulation, and photothermal activation.
Ziyi Zhao, Yanxiang Sang, Benyan Zheng et al.· International Journal of Bio...· 0 citations
