Aug 2026· ACS Applied Materials and Interfaces· 0 citations· 66 references
Medicine
TL;DR
Both in vitro and diabetic in vivo models demonstrate efficient bacterial elimination, inflammation suppression, and enhanced re-epithelialization and neovascularization, ultimately accelerating wound repair, establishing a highly integrated nanozyme-enabled therapeutic paradigm for the localized treatment of infected diabetic wounds.
Abstract
Chronic diabetic wounds represent a severe complication of diabetes mellitus and a prototypical form of chronic nonhealing wounds, characterized by biofilm-associated infection, persistent inflammation, and impaired angiogenesis. Herein, a multifunctional microneedle platform incorporating cationic chitosan-coated ruthenium dioxide nanozymes (RuO2@QCS NPs), termed RuO2@QCS-MN, is developed to accelerate diabetic wound healing through microenvironment reprogramming. This integrated system combines photothermal antibacterial activity, reactive oxygen species (ROS) scavenging, and in situ oxygen generation to coordinately regulate the pathological milieu of infected wounds. The microneedles effectively penetrate bacterial biofilms and deliver nanozymes to bacteria-enriched regions, enabling efficient yet mild photothermal antibacterial therapy. Meanwhile, RuO2@QCS NPs exhibit catalase-like activity, catalyzing endogenous hydrogen peroxide into oxygen, thereby enhancing nanozyme diffusion, alleviating oxidative stress, modulating inflammatory responses, and promoting macrophage polarization. Simultaneous oxygen generation may alleviate hypoxia and promote angiogenic responses. Both in vitro and diabetic in vivo models demonstrate efficient bacterial elimination, inflammation suppression, and enhanced re-epithelialization and neovascularization, ultimately accelerating wound repair. This work establishes a highly integrated nanozyme-enabled therapeutic paradigm for the localized treatment of infected diabetic wounds.
This work developed a synergistic single-platform strategy for precise regulation of diabetic wound microenvironments, providing a promising therapeutic alternative for refractory diabetic wound treatment.
Diabetic wounds exhibit prolonged inflammation and excessive oxidative stress, impairing tissue repair. Chronic hypoxia arises from vascular dysfunction and metabolic dysregulation, creating a pathological cycle of oxidative damage, defective angiogenesis, and persistent inflammation. To address these challenges, we develop the multifunctional rosmarinic acid-cerium nanozyme (RA-Ce NP) hydrogel composites designed for diabetic wound therapy. The system integrates RA-Ce NPs, phenylboronic acid-grafted poly-l-lysine, and oxidized hyaluronic acid into a dynamically crosslinked hydrogel network through Schiff base and boronate ester linkages. Both in vitro and in vivo studies demonstrate that the hydrogel enables multienzyme mimicry for synergistic reactive oxygen species scavenging, controlled oxygen generation to relieve tissue hypoxia, and promotion of neovascularization. Our work provides a clinically translatable platform for diabetic wound therapy, offering antibacterial, anti-inflammatory, and angiogenesis-promoting functions.
Junjie Wang, Zhijun You, Ling Zhou et al.· ACS Applied Materials and In...· 0 citations
Persistent hyperglycemia and alkaline microenvironments in chronic diabetic wounds promote bacterial resistance, continuous inflammation, and delayed wound repair. Herein, a thermosensitive hydrogel, integrating zirconium-based metal-organic framework (Zr-MOF)-loaded glucose oxidase (GOx) nanozyme and l-arginine (l-Arg), is developed for diabetic wound microenvironment remodeling and moist healing. Upon encountering glucose, GOx neutralizes hyperglycemia, producing gluconic acid to lower the wound pH and generating hydrogen peroxide (H2O2). The resulting acidic wound environment activates the peroxidase (POD)-like activity of Zr-MOFs, generating highly toxic hydroxyl radicals that eliminate bacterial biofilms. The excess H2O2 drives the conversion of l-Arg into nitric oxide, preventing excessive reactive oxygen species accumulation and promoting angiogenesis, epithelialization, and collagen deposition. Experiments demonstrate that the prepared hydrogel effectively reverses both the alkaline pH and hyperglycemia conditions characteristic of diabetic wounds, significantly accelerating the healing of bacteria-infected chronic diabetic wounds and providing an approach for chronic wound management.
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
In diabetic wounds, diverse reactive oxygen species (ROS) intertwine to form a complex oxidative stress network, directly causing damage to cells and tissues. Most single-therapy materials fail to fully regulate this complex oxidative stress microenvironment, hindering wound healing. In this study, a nanozyme-hydrogel composite system was constructed. Through the complementarity of photothermal and enzyme-catalytic functions, cellular functions were enhanced while the oxidative stress microenvironment of diabetic wounds was alleviated, thereby collectively promoting wound healing. A cerium oxide (CeO2)-based nanozyme with abundant oxygen vacancies and high photothermal efficiency was fabricated via gadolinium (Gd) doping and platinum (Pt) nanocluster modification. Gd doping enhanced the catalase (CAT) -mimetic activity by increasing oxygen vacancies, while Pt nanoclusters enabled photothermal conversion. Through this functional complementarity, efficient wound regulation was achieved. To ensure stable retention, the nanozyme (GCP) was loaded into an in situ photo-cross-linkable hydrogel to form the GCP@PG dressing. In vitro and in vivo, GCP@PG scavenged intracellular ROS and promoted angiogenesis. In diabetic rats with full-thickness skin defects, the wound closure rate reached 97.95% on day 14. By integrating the functional complementarity of enzyme catalysis and photothermal effects, this composite system provides a strategy for diabetic wound repair.
Yang Yang, Dinping She, Shuya Zhang et al.· Chemistry of Materials· 0 citations
A precision-engineered hydrogel that integrates structural integrity with environment-triggered delivery and seamlessly coupling nanocontrolled release with microenvironmental sensing is presented, presenting a precision-engineered platform for the synergistic treatment of recalcitrant diabetic wounds.
