Bacteria microenvironment-responsive missile microneedles modulate immunity and penetrate biofilm for diabetic wound therapy
Ganghua Yang, Haowen Kang, Yuanzheng Zhu, Hengyu Wu, Minchen Zhang, Xinghong Zeng, Ying Peng, Wenbing Wan, Yangyan Yi
Abstract
Diabetic wounds, affecting ∼25 % of patients with diabetes, present a therapeutic challenge due to persistent inflammation driven by MCP-1-mediated immune dysregulation and bacterial biofilm formation. We developed a bilayer microneedle system (DAg/HTMS-MNs) combining dextran-modified silver nanoparticles for deep-tissue antibacterial action with heparin-coated taurine-loaded microspheres for immunomodulation. The upper microneedle segment enables biofilm penetration through lectin targeting and gas propulsion, while the lower segment implements a "global decompression-local enhancement" strategy: heparin sequesters MCP-1 to reduce inflammatory cell recruitment, and sustained taurine release promotes macrophage reprogramming to M2 phenotypes. Systematic evaluation demonstrated simultaneous biofilm eradication, inflammation resolution (2-fold enhanced M2 polarization), and accelerated wound healing. This "missile-guided" approach represents a paradigm shift in diabetic wound therapy by concurrently addressing infection control, oxidative stress, and immune dysregulation in a spatially and temporally controlled manner.