Dual ROS/pH-responsive mangiferin-loaded smart microneedles for precision therapy of wound infections

Infected wound healing remains critically challenged by persistent bacterial biofilms and dysregulated inflammation, whereas conventional silver dressings lack dynamic microenvironment responsiveness and fail to synergize antibacterial efficacy with tissue regeneration. Although conventional silver dressings offer proven antibacterial efficacy, their static nature limits dynamic microenvironment adaptation and synergistic tissue regeneration. To resolve these limitations, we developed an intelligent microneedle patch (PCMA MN) integrating a pH/reactive oxygen species (ROS)-dual-responsive hydrogel matrix composed of gallic acid-grafted chitosan (CG) and TSPBA-crosslinked polyvinyl alcohol (PT) for on-demand drug release, mangiferin (MF)-loaded PLGA microspheres for promoting angiogenesis, and a synergistic silver-gallic acid antibacterial coating. PCMA MNs demonstrated bactericidal capacity comparable to silver dressings, while significantly accelerating wound closure by 14.25%. This regenerative improvement was driven by enhanced angiogenesis and dynamic macrophage polarization toward regenerative M2 phenotypes, which collectively resolved inflammation and facilitated collagen deposition. Our bioresponsive platform establishes a novel strategy coordinating real-time pharmacokinetics with pro-regenerative immunomodulation, offering transformative potential for complex wound management. • Infected wound healing remains critically compromised by persistent biofilms and dysregulated inflammation. Although conventional silver dressings demonstrate proven antibacterial efficacy, their static nature impedes dynamic adaptation to evolving wound microenvironments and fails to synchronize rapid pathogen eradication with pro-regenerative immunomodulation, ultimately limiting tissue repair outcomes . To address these dual challenges, we engineered an intelligent microneedle patch (PCMA MNs) integrating a pH/reactive oxygen species (ROS)-dual-responsive hydrogel matrix of gallic acid-grafted chitosan (CG) and TSPBA-crosslinked polyvinyl alcohol (PT) for on-demand drug release, mangiferin (MF)-loaded PLGA microspheres to promote angiogenesis, and a synergistic silver-gallic acid coating for rapid biofilm disruption. This design establishes a spatiotemporal therapeutic cascade: initial Ag + burst release achieves bactericidal efficiency comparable to silver dressings, while subsequent pH/ROS-triggered MF release accelerates angiogenesis and dynamically shifts macrophages toward regenerative M2 phenotypes, thereby resolving inflammation and facilitating collagen deposition. Collectively, PCMA MNs demonstrate significant clinical advantages by accelerating wound closure by 14.25% over conventional antimicrobial therapies, representing a transformative strategy that coordinates real-time pharmacokinetics with immunomodulatory regeneration for complex wound management.