Abstract
Diabetic wounds require continuous and coordinated modulation of the microenvironment concurrent with tissue regeneration, which remains a significant challenge. As a proof of concept, we herein propose to use dimeric copper peptide (D-CuP) for diabetic wound treatment. The D-CuP is synthesized and then incorporated into a reactive oxygen species (ROS)-responsive hydrogel matrix to improve therapeutic compliance, culminating in the formulation of G/D-CuP. Compared to monomer copper peptide (M-CuP), a wound healing agent, D-CuP exhibits multivalency, enhanced biological stability against proteases, and broad biological activities. Meanwhile, the hydrogel matrix, exhibiting ROS-scavenging capabilities, has been engineered to be an intelligent drug reservoir for wound-responsive release of D-CuP at the wound site while simultaneously attenuating inflammatory responses. Ultimately, the G/D-CuP group demonstrates superior therapeutic efficacy, achieving 97.2% closure of infected wounds.