Nanozyme-driven multifunctional dressings: moving beyond enzyme-like catalysis in chronic wound treatment

Abstract

The treatment of chronic wounds presents significant challenges due to the necessity of accelerating healing within complex microenvironments characterized by persistent inflammation and biochemical imbalances. Factors such as bacterial infections, hyperglycemia, and oxidative stress disrupt cellular functions and impair angiogenesis, substantially delaying wound repair. Nanozymes, which are engineered nanoscale materials with enzyme-like activities, offer distinct advantages over conventional enzymes and traditional nanomaterials, making them promising candidates for chronic wound treatment. To enhance their clinical potential, nanozyme-based catalytic systems are currently being optimized through formulation advancements and preclinical studies assessing their biocompatibility, anti-oxidant activity, antibacterial efficacy, and tissue repair capabilities, ensuring their safety and clinical applicability. When integrated into multifunctional wound dressings, nanozymes modulate reactive oxygen species levels, promote tissue regeneration, and simultaneously combat infections and oxidative damage, extending beyond conventional enzyme-like catalysis in chronic wound treatment. The customizable architectures of nanozymes enable precise therapeutic applications, enhancing their effectiveness in managing complex wound conditions. This review provides a comprehensive analysis of the incorporation of nanozymes into wound dressings, detailing fabrication methods and emphasizing their transformative potential in chronic wound management. By identifying and addressing key limitations, we introduce strategic advancements to drive the development of nanozyme-driven dressings, paving the way for next-generation chronic wound treatments.

Keywords: Chronic wound therapy; Enzyme-like activities; Multifunctional wound dressing; Nanozyme; Reactive oxygen species regulation.

Fig. 1

Overall wound healing progress. a Hemostasis begins with platelet aggregation to prevent blood loss, resulting in the formation of an initial fibrin framework. b The inflammatory phase is triggered by immune receptors that detect pathogens, leading to immune cell recruitment and pro-inflammatory signaling. c In the proliferative phase, fibroblasts, keratinocytes, and vascular endothelial cells form granulation tissue to promote extracellular matrix (ECM) remodeling. Meanwhile, macrophages secrete vascular endothelial growth factor (VEGF) to promote angiogenesis, facilitating the transport of oxygen to the wound site and recovering energy supply. d The remodeling phase is characterized by the continued synthesis and degradation of collagen in the ECM. Cytokines (especially TGF-β) stimulate fibroblasts to produce collagen, which is then broken down by enzymes to restore the normal structure of the dermis. TNF-α tumor necrosis factor-α, IL interleukin, ROS reactive oxygen species, TGF-β transforming growth factor-β, TIMP-1 tissue inhibitor of metallopeptidase-1

Fig. 2

Overview of nanozyme-based therapeutic mechanisms for wound healing. Before treatment, pathogenic infections activate immune cells to infiltrate the wound site and release abundant antibacterial substances, but the biofilm formed by bacterial accumulation protects the bacteria, resulting in persistent inflammation. Furthermore, oxidative stress impedes angiogenesis and damages dermal cells, complicating tissue regeneration and prolonging the healing process. In contrast, nanozymes have the potential to modify the wound microenvironment. Their enzyme-like activity adapts to pH changes: under acidic conditions, they increase pro-oxidant activity to combat infection, whereas in alkaline environments, they shift toward anti-oxidant activity, reducing oxidative stress and inflammation. This dual functionality fosters a more conducive healing environment and promotes tissue regeneration. ROS reactive oxygen species, VEGF vascular endothelial growth factor, POD peroxidase, OXD oxidase, SOD superoxide dismutase, CAT catalase