Bacteria microenvironment-responsive missile microneedles modulate immunity and penetrate biofilm for diabetic wound therapy.

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.