A self-assembly enzyme-like hydrogel with ROS scavenging and immunomodulatory capability for microenvironment-responsive wound healing acceleration

Abstract

On-demand responsive hydrogels are a promising solution for effective wound management as they can adjust their properties in response to changes in the wound environment, allowing them to provide tailored support for the healing process. However, the conventional hydrogels may not fully meet the diverse demands of the intricate healing process. Herein, a novel glycyrrhizic acid (GA) based self-assembly hydrogel coordinated with copper and polyphenol (GCP hydrogel) was developed to exhibit triggered release behavior in response to the microenvironment. The GCP hydrogel coordinated with copper and protocatechuic acid (PA) and self-assembled with GA, also exhibits enzyme-like properties by mimicking the cascade process of superoxide dismutase (SOD) and catalase (CAT), effectively scavenging reactive oxygen species (ROS). Furthermore, the on-demand release of Cu²⁺ at different stages of the wound healing process can not only enhance the antibacterial ability of methicillin-resistant Staphylococcus aureus (MRSA) but also intelligently promote angiogenesis with outstanding biocompatibility. In addition, the GCP hydrogel effectively modulated the activity of macrophages in response to inflammatory stimuli, exhibiting remarkable anti-inflammatory abilities and promoting tissue regeneration. The multifunctional GCP hydrogel platform has the potential to create a dynamic microenvironment that is conducive to tissue regeneration, making it an ideal candidate for smart wound management.