Abstract

Infected burn wounds are difficult to heal due to a self-sustaining cycle of infection, inflammation, oxidative stress, and pain that disrupts orderly tissue regeneration. Herein, we develop a programmable marine polysaccharide-based core-shell microneedle patch (CC-MN) that effectively disrupts this pathological cycle through stage-specific therapeutic regulation. The CC-MN integrates a chito-oligosaccharide (COS) shell and a chondroitin sulfate (CS) core. Its programmability is encoded by the core-shell architecture, enabling rapid COS shell dissolution for early-stage antibacterial intervention, followed by sustained CS core release for prolonged immunomodulatory and pro-regenerative regulation. Specifically, CC-MN achieved antibacterial inhibition rates of 94.0%, 98.8%, and 99.5% against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, respectively. Meanwhile, sustained CS release attenuated inflammation, scavenged excessive reactive oxygen species, reduced pain-associated inflammatory mediators including prostaglandin E2, and promoted macrophage polarization toward a pro-regenerative phenotype. In a Pseudomonas aeruginosa-infected burn wound model, CC-MN treatment reduced wound bacterial burden to ~0.5% of the untreated control and accelerated wound closure to 96.1% by day 16, accompanied by decreased inflammatory cytokine expression, enhanced angiogenesis, and improved collagen remodeling. This work presents a translatable and programmable microneedle platform for comprehensive management of infected burn wounds.