Phase‐Programmed Microneedles Enable Sequential Hydrogen and Quercetin Release for Scar‐Reduced Regeneration of Burn Wounds
Yongnian Zeng, Zhigang Chu, Huiyuan Yang, Wen Zhang, Peng Jiang, Jiapeng Lei, Siyu Zhang, Qiongfang Ruan, Shuhua Liu, Wei LiABSTRACT
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 H 2 ‐releasing prodrug AB. Upon exposure to the mildly acidic wound microenvironment, the system triggers sustained generation of hydrogen (H 2 ) 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.