Le Deng

Diabetic wounds represent a significant clinical challenge due to a complex pathological microenvironment marked by hyperglycemia, persistent inflammation, and high susceptibility to infection. Metal composite hydrogels have emerged as a next-generation therapeutic platform that uniquely combines the multifaceted capabilities of metal components, such as potent antibacterial, anti-inflammatory, and antioxidant activities, with the ideal moist healing properties of hydrogels. This review focuses on recent progress in the design strategies for these materials, including physical, chemical, and hybrid doping methods. The review then details their multimodal mechanisms of action, including direct antibacterial pathways, like reactive oxygen species generation and photothermal therapy, along with immunomodulatory interventions that regulate macrophage polarization and resolve chronic inflammation. Furthermore, their role in promoting tissue repair processes, such as angiogenesis and collagen remodeling, is discussed. Finally, the review critically examines prevailing challenges and future directions concerning biosafety, scalable fabrication, and clinical translation, with the goal of providing a comprehensive reference for advancing novel therapies for diabetic wound care.

Purpose: We aimed to develop an oxidative-stress-activated palladium-copper nanozyme to reduce bacterial’s heat sensitivity by down-regulating heat shock proteins to overcome the shortcomings of conventional photothermal antimicrobial therapy and achieve mild photothermal bactericidal efficacy. Methods: We first synthesized palladium-copper nanozymes (PC-NPs) by hydration and used transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy to demonstrate their successful preparation. Their photothermal therapy (PTT) and chemo-dynamic therapy (CDT) activities were then determined by a series of photothermal performance tests and peroxidase-like performance tests, and the destruction of heat shock proteins by reactive oxygen species (ROS) was verified at the protein level by Western Blotting tests, providing a basis for the effective bacteria-killing by the mild-temperature photothermal treatment subsequently applied. We also validated this promising programmed and controlled antimicrobial treatment with palladium-copper nanozymes by in vivo/in vitro antimicrobial assays. A hemolysis assay, MTT cytotoxicity test and histopathological analysis were also performed to assess the in vivo safety of PC-NPs. Results: In the micro-acidic environment of bacterial infection, PC-NPs showed peroxidase-like activity that broke down the H₂O₂ at the wound into hydroxyl radicals and down-regulated bacterial heat shock proteins. The application of PC-NPs increased bacteria’s sensitivity to subsequent photothermal treatment, enabling the elimination of bacteria via mild photothermal treatment. Conclusion: The programmed synergistic catalytic enhancement of CDT and mild photothermal therapy achieves the most efficient killing of bacteria and their biofilms, which brings future thinking in the relationship between heat shock proteins and oxidative stress damage in bacteria.

Preventing bacterial infections and accelerating wound closure are essential in the process of wound healing. Current wound dressings lack enough mechanical properties, self-healing ability, and tissue adhesiveness, and the bacterial killing also relies on the use of antibiotic drugs. Herein, a well-designed hybrid hydrogel dressing is constructed by simple copolymerization of acrylamide (AM), 3-acrylamido phenylboronic acid (AAPBA), chitosan (CS), and the nanoscale tannic acid (TA)/ferric ion (Fe³⁺) complex (TFe). The resulting hydrogel possesses lots of free catechol, phenylboronic acid, amine, and hydroxyl groups and contains many reversible and dynamic bonds such as multiple hydrogen bonds and boronate ester bonds, thereby showing satisfactory mechanical properties, fast self-healing ability, and desirable tissue-adhesive performance. Benefiting from the high photothermal conversion efficiency of the TFe, the hydrogel exhibits satisfactory antibacterial activity against both Gram-positive and Gram-negative bacteria. Moreover, the embedded TFe also endows the hydrogel with good antioxidant activity, anti-inflammatory property, and cell proliferation to promote tissue regeneration. Remarkably, in vivo animal assays reveal that the hybrid hydrogel effectively eliminates biofilm bacteria in the wound sites and accelerates the healing process of infected wounds. Taken together, the developed versatile hydrogels overcome the shortcomings of traditional wound dressings and are expected to become potential antibacterial dressings for future biomedical applications.

Pathogenic bacterial infections of skin wounds have caused a significant threat to clinical treatment and human life safety. Here, we develop a bactericidal hydrogel dressing consisting of a polyacrylamide (PAM) hydrogel framework with in situ surface-deposition of iron-dopped polydopamine (FePDA). The prepared hydrogel dressing (FePDA-PAM) has a compact surface, good tensile strength, and excellent elastic recovery ability. The introduction of Fe³⁺ ions improve the photothermal therapy (PTT) efficiency of the PDA and endow the hydrogel dressing with chemodynamic therapy (CDT) properties. In vitro experiments show that the antibacterial effect of FePDA-PAM hydrogel on Staphylococcus aureus reach nearly 100% under the combined action of H₂O₂ and 808 nm near-infrared (NIR) laser, indicating an excellent combined antibacterial property of PTT and CDT. Furthermore, the FePDA-PAM + H₂O₂ + NIR treatment group in the in vivo antibacterial experiments displays lowest relative wound area and optimal wound healing within 5 days of treatment, thereby indicating the intensive skin wound disinfection. To summarize, the FePDA-PAM hydrogel has simple preparation and good biosafety. It may serve as a potential wound dressing for the combined PTT/CDT dual-mode antibacterial therapy.

We rationally construct a biofilm microenvironment-responsive bactericidal nanoplatform (ZnPMp) consisting of ZnO core, a Fe ³⁺ -doped polydopamine coating and methylene blue (MB) payload for combined CT/CDT/PTT/PDT multi-mode antibacterial therapy.