Stage-Responsive Multifunctional Microneedle Patches for Enhanced Biofilm Penetration and Accelerated Healing of Bacterial Infected Skin Wounds.

Biofilms, formed by microorganisms and surrounding substances, hinder traditional drug delivery and delay wound healing. Microneedles, with their excellent mechanical properties, minimally invasive nature, and ability to penetrate biofilms for rapid drug delivery, offer a promising solution for biofilm eradication. In this study, we developed an intelligent, responsive bilayer microneedle system (CurMN@RRH) based on photodynamic therapy to accelerate wound healing caused by bacterial infections. Cur@ZIF-8 nanoparticles are synthesized in a one-pot process and embedded in gelatin and hyaluronic acid to form the microneedle tips. The microneedle substrate consists of ROS-responsive boronate-ester-based hydrogels (TSPBA-PVA), loaded with the antioxidant glutathione (GSH). In the early stages of wound healing, the acidic environment triggered by bacterial infection prompts the release of curcumin from Cur@ZIF-8 nanoparticles, which generates hydroxyl radicals under blue light to promote bacterial death. In later stages, the CurMN@RRH microneedles release GSH, clearing excessive reactive oxygen species and reducing inflammation, thus accelerating healing. Both in vitro and in vivo experiments demonstrate that the intelligent CurMN@RRH microneedles exhibited strong antibacterial, anti-inflammatory, and antioxidant properties, promoted cell proliferation, and accelerated tissue wound healing. This approach offers a novel strategy for treating bacterial infection-induced wounds.