Oxidative stress is associated with many acute and chronic inflammatory diseases, yet limited treatment is currently available clinically. The development of enzyme-mimicking nanomaterials (nanozymes) with good reactive oxygen species (ROS) scavenging ability and biocompatibility is a promising way for the treatment of ROS-related inflammation. Herein we report a simple and efficient one-step development of ultrasmall Cu_5.4O nanoparticles (Cu_5.4O USNPs) with multiple enzyme-mimicking and broad-spectrum ROS scavenging ability for the treatment of ROS-related diseases. Cu_5.4O USNPs simultaneously possessing catalase-, superoxide dismutase-, and glutathione peroxidase-mimicking enzyme properties exhibit cytoprotective effects against ROS-mediated damage at extremely low dosage and significantly improve treatment outcomes in acute kidney injury, acute liver injury and wound healing. Meanwhile, the ultrasmall size of Cu_5.4O USNPs enables rapid renal clearance of the nanomaterial, guaranteeing the biocompatibility. The protective effect and good biocompatibility of Cu_5.4O USNPs will facilitate clinical treatment of ROS-related diseases and enable the development of next-generation nanozymes.

Hydrogels are promising and widely utilized in the biomedical field. In recent years, the anti‐inflammatory function of hydrogel dressings has been significantly improved, addressing many clinical challenges presented in ongoing endeavours to promote wound healing. Wound healing is a cascaded and highly complex process, especially in chronic wounds, such as diabetic and severe burn wounds, in which adverse endogenous or exogenous factors can interfere with inflammatory regulation, leading to the disruption of the healing process. Although insufficient wound inflammation is uncommon, excessive inflammatory infiltration is an almost universal feature of chronic wounds, which impedes a histological repair of the wound in a predictable biological step and chronological order. Therefore, resolving excessive inflammation in wound healing is essential. In the past 5 years, extensive research has been conducted on hydrogel dressings to address excessive inflammation in wound healing, specifically by efficiently scavenging excessive free radicals, sequestering chemokines and promoting M₁‐to‐M₂ polarization of macrophages, thereby regulating inflammation and promoting wound healing. In this study, we introduced novel anti‐inflammatory hydrogel dressings and demonstrated innovative methods for their preparation and application to achieve enhanced healing. In addition, we summarize the most important properties required for wound healing and discuss our analysis of potential challenges yet to be addressed.

Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt to diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) and alternatively activated (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay of signaling pathways, transcriptional regulators, and epigenetic modifications orchestrates macrophage polarization, allowing them to respond to various stimuli dynamically. Here, we provide a comprehensive overview of the signaling cascades governing macrophage plasticity, focusing on the roles of Toll‐like receptors, signal transducer and activator of transcription proteins, nuclear receptors, and microRNAs. We also discuss the emerging concepts of macrophage metabolic reprogramming and trained immunity, contributing to their functional adaptability. Macrophage plasticity plays a pivotal role in tissue repair and regeneration, with macrophages coordinating inflammation, angiogenesis, and matrix remodeling to restore tissue homeostasis. By harnessing the potential of macrophage plasticity, novel therapeutic strategies targeting macrophage polarization could be developed for various diseases, including chronic wounds, fibrotic disorders, and inflammatory conditions. Ultimately, a deeper understanding of the molecular mechanisms underpinning macrophage plasticity will pave the way for innovative regenerative medicine and tissue engineering approaches.

A desirable microenvironment is essential for wound healing, in which an ideal moisture content is one of the most important factors. The fundamental function and requirement for wound dressings is to keep the wound at an optimal moisture. Here, we prepared serial polyurethane (PU) membrane dressings with graded water vapor transmission rates (WVTRs), and the optimal WVTR of the dressing for wound healing was identified by both in vitro and in vivo studies. It was found that the dressing with a WVTR of 2028.3 ± 237.8 g/m²·24 h was able to maintain an optimal moisture content for the proliferation and regular function of epidermal cells and fibroblasts in a three-dimensional culture model. Moreover, the dressing with this optimal WTVR was found to be able to promote wound healing in a mouse skin wound model. Our finds may be helpful in the design of wound dressing for wound regeneration in the future.