Dual-responsive copper complex delivered by dissolvable microneedle promotes polymicrobial infection eradication and cutaneous wound healing

Abstract

Cross-kingdom polymicrobial wound infections present significant clinical challenges, including persistent pathogen colonization, delayed healing, and an elevated risk of complications. Despite the broad-spectrum antimicrobial activity and immunomodulatory properties of copper ions (Cu²⁺), their therapeutic efficacy in infectious wound management is often suboptimal due to the lack of precise control of ion release kinetics. Here, we developed a dissolvable microneedle dressing loaded with our novel copper complex containing an Azo-Schiff base (Cu-Azo@DMN). This system demonstrates oxidative stress-mediated antimicrobial activity and enables pH-responsive Cu²⁺ release in the acidic polymicrobial infection microenvironment. Furthermore, Cu-Azo@DMN also exhibits enhanced antimicrobial efficacy through photo-responsive Cu²⁺ release. Following pathogen clearance, the system autonomously tunes down Cu²⁺ release to resolve inflammation and promote angiogenesis, thereby facilitating tissue regeneration. Collectively, our findings feature Cu-Azo@DMN as a smart wound dressing that enables dual-responsive Cu²⁺ release, offering a streamlined management of cross-kingdom polymicrobial infections and immunomodulation wound healing.