Phase-Programmed Microneedles Enable Sequential Hydrogen and Quercetin Release for Scar-Reduced Regeneration of Burn Wounds

Burn wounds complicated by bacterial infection and fibrotic scarring remain a major clinical challenge, demanding therapeutics capable of coordinated infection control, inflammation modulation, and tissue regeneration. Here, we report a phase-programmed microneedle (MN) patch (QR/AB-MNs) that enables spatiotemporally controlled release of ammonia borane (AB) and quercetin (QR) to achieve synergistic antimicrobial and anti-fibrotic therapy. The MNs comprise a poly (lactic-co-glycolic acid) (PLGA) shell encapsulating QR and a sulfobutylether-β-cyclodextrin (SBECD) core loaded with the H₂-releasing prodrug AB. Upon exposure to the mildly acidic wound microenvironment, the system triggers sustained generation of hydrogen (H₂) and AB degradation products, effectively eliminating bacteria and biofilms while mitigating oxidative stress. Subsequently, gradual PLGA degradation ensures prolonged QR release, suppressing fibroblast hyperproliferation and TGF-β mediated collagen deposition, thereby preventing hypertrophic scarring. In murine and rabbit burn models, QR/AB-MNs markedly accelerated wound closure, reduced inflammation and bacterial burden, restored skin appendages, and yielded scar-reduced regeneration with native-like collagen architecture. Transcriptomic profiling further revealed that QR/AB-MNs orchestrate a broad anti-fibrotic transcriptional program, concurrently attenuating pro-fibrotic signaling, cell-extracellular matrix interactions, and collagen synthesis. Collectively, this programmable MN platform integrates redox modulation, anti-infective therapy, and matrix remodeling to achieve comprehensive, scarless-like healing of infected burn wounds.