In a mouse model of MRSA‐infected wounds, treatment with CPAM/GS hydrogel‐NIR(+) significantly accelerated wound healing, eliminated bacteria, and modulated wound microenvironment by reducing pro‐inflammatory cytokines and promoting angiogenesis.
Abstract
The rise of multidrug‐resistant bacterial infections and biofilms poses a significant challenge to wound healing. Herein, we developed a temperature‐responsive gel–sol phase‐transition multifunctional hydrogel, named CPAM/GS, by incorporating a novel nanozyme, CeO2@PtAu@Mn2(CO)10, into a gelatin/sodium alginate matrix. The synthesized CeO2@PtAu@Mn2(CO)10 nanozyme exhibits multi‐enzyme activities, including peroxidase‐, oxidase‐, and catalase‐like properties, enabling it to generate ROS in response to the pH of the infected microenvironment and supply oxygen under hypoxic conditions. The CPAM/GS hydrogel demonstrates excellent photothermal performance (η = 47.99%) and allows on‐demand release of carbon monoxide (CO) and nanozymes upon NIR irradiation. In vitro experiments confirmed its potent antibacterial efficacy against methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa through the synergistic effects of photothermal therapy, chemodynamic therapy, and CO gas therapy, achieving a 100% and 99.8% antibacterial rate under NIR irradiation. Furthermore, this hydrogel effectively disrupts preformed biofilms, suppresses virulence gene expression, and promotes cell migration. In a mouse model of MRSA‐infected wounds, treatment with CPAM/GS hydrogel‐NIR(+) significantly accelerated wound healing, eliminated bacteria, and modulated wound microenvironment by reducing pro‐inflammatory cytokines and promoting angiogenesis. Its excellent biosafety and hemostatic performance were also confirmed. This work proposes a multifunctional synergistic strategy for treating multidrug‐resistant bacterial infections and promoting wound regeneration.
This work demonstrates a safe and effective strategy for combating MDR infections through the combined action of photothermal therapy and nanozyme catalysis, offering promising potential for clinical wound management.
Weiwei Zhang, Lixiang Fan, Xuanjun Zhang et al.· ACS Applied Materials and In...· 0 citations
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.
Songjie Li, Han Chen, Xin Dan et al.· Nano Reseach· 0 citations
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 infected with methicillin‐resistant
Staphylococcus aureus
(MRSA) pose a significant challenge to clinical healing. Proliferating MRSA not only invades neutrophils to induce immunosuppression but also produces hydrogen sulfide (H
2
S) and forms biofilms to enhance its resistance to antimicrobial agents. Herein, three AgTCPP‐BiMOF‐2dDR (PBMD‐1/2/3) particles with cubic, rhombohedral and urchin‐like morphologies are designed as bacteria‐derived H
2
S scavengers to induce N1 neutrophil polarization. Among these morphologies, the formation of heterogeneous structure between urchin‐like PBMD‐3 and in situ produced Bi
2
S
3
enables bandgap modulation, enhancing photodynamic (55.55%, ·OH conversion rate) and photothermal (11.75%) conversion efficiencies under 650/980 nm laser irradiation, respectively. Additionally, more bismuth active sites in the urchin‐like structure significantly boost H
2
S‐scavenging activity, thereby leading to the high expression of the N1 marker CD54 (24.4%). Capitalizing on these merits, urchin‐like PBMD‐3 exhibits the most prominent therapeutic effect, with eradication rates of MRSA and biofilms being nearly 100% in vitro. With catalase (CAT)‐like activity, dual‐metal (Ag/Bi) PBMD‐3 converts endogenous H
2
O
2
into dissolved oxygen to alleviate ROS accumulation and hypoxia. In a MRSA‐infected rat skin wound model, PBMD‐3A hydrogel shows prominent wound healing with negligible systemic toxicity. This work establishes a novel morphology‐dependent immunotherapeutic strategy for the treatment of MRSA‐infected diabetic wounds.
Chronic wounds remain a major clinical challenge due to persistent inflammation, excessive oxidative stress, and impaired tissue regeneration. Herein, we developed a multifunctional hydrogel dressing (GX/ML) by integrating a reactive oxygen species (ROS)‐responsive dynamic borate ester cross‐linking network with electrocatalytic MXene nanosheets and anti‐inflammatory luteolin. The hydrogel enables real‐time monitoring of wound inflammation through electrochemical sensing of H2O2 levels, while on‐demand drug release is triggered by either high ROS or near‐infrared irradiation. In vitro and in vivo results demonstrated exceptional ROS‐scavenging capability, efficient antibacterial activity (>96% against S. aureus and E. coli), and promotion of macrophage polarization toward the pro‐healing M2 phenotype. In a diabetic mouse wound model, the GX/ML hydrogel accelerated wound closure (98.1% healing rate by day 19), enhanced angiogenesis, collagen deposition, and re‐epithelialization, and modulated immune responses via cytokine signaling pathways (e.g., NF‐κB and NOD‐like receptor pathways). Transcriptomic analysis confirmed regulation of genes related to immune inflammation and tissue remodeling. This work provides a synergistic strategy through a smart hydrogel platform that integrates real‐time inflammatory monitoring with condition‐triggered drug release, offering a feedback‐responsive approach for chronic wound management.
Hua Wei, Hongyu Zhao, Xiao-Han Li et al.· Aggregate· 1 citation
In this report, hydrogels were combined with silver nanoparticles to impart antibacterial properties, yielding robust materials that prevent bacterial infections while maintaining stimulus responsiveness. The antibacterial hydrogel was based on double‐network (DN) hydrogels and prepared via in situ reduction of silver nitrate to silver nanoparticles (AgNPs). The DN hydrogel consists of polyvinyl alcohol‐co‐glutaraldehyde and poly(acrylamide‐co‐sodium acrylate‐co‐N‐isopropylacrylamide), serving as the first and second networks, respectively. The FT‐IR, x‐ray diffraction, and TEM analysis revealed the successful incorporation of silver nanoparticles within the DN hydrogel. The stimulus responsiveness of these hydrogels was assessed through temperature‐ and pH‐dependent swelling, and their thermal properties were also evaluated. The antibacterial efficacy of AgNPs embedded in DN hydrogels was validated by optical density (OD600) measurements in suspension culture, which confirmed significant growth inhibition of both Escherichia coli (Gram‐negative) and Staphylococcus aureus (Gram‐positive) bacteria. Interestingly, the assessment of antibacterial activity using an agar diffusion assay with silver nanoparticle‐loaded hydrogels also revealed excellent bacterial growth inhibition against both Escherichia coli and Staphylococcus aureus (p < 0.0001). Hydrogels also showed notable cytocompatibility. These findings highlight the potential of AgNPs‐embedded stimuli‐responsive DN nanocomposite hydrogels, which may serve as promising materials for various biomedical products that require an antibacterial microenvironment.
