Dynamic enzyme-mimetic peptide hydrogel for the treatment of bacterial-infected inflammatory wounds

Peptide-based hydrogels offer biocompatibility and sequence flexibility for wound healing, yet dynamically regulating therapy within the complex wound microenvironment remains challenging. Inspired by natural silk protein and copper-peptide complexes, we designed an amphiphilic peptide that can self-assemble into active center structures similar to natural enzymes, and further form stable hydrogel networks. After coordination with copper ions, the system demonstrates dynamically regulated dual antioxidase activities: superoxide dismutase (SOD)-like behavior under weakly alkaline conditions and peroxidase (POD)-like activity under acidic conditions. This pH-regulated activity conversion process closely mirrors the pH fluctuations commonly observed in infected and inflamed wound sites, enabling real-time adaptation to local microenvironmental changes. In addition, this enzyme-mimicking hydrogel exhibits efficient reactive oxygen species (ROS) scavenging capability and notable antibacterial performance, effectively promoting wound closure and the formation of skin appendages in a bacterial-infected inflammatory wound model. It also exhibits good mechanical properties, especially in terms of self-healing properties and injectability, showing promising prospects for engineering applications. This versatile hydrogel platform, capable of precisely mimicking and dynamically regulating the activity of key enzymes involved in the wound healing process, offers a promising strategy for modulating the wound microenvironment and promoting a more efficient cascade of healing responses. Meanwhile, this work clarifies the structure-activity relationship between the colloidal self-assembly of amphiphilic peptides and the biochemical interface properties of hydrogels, thereby expanding the theoretical framework for designing and controlling biocatalytic interfacial colloidal materials.