Phase-Programmed Microneedles Enable Sequential Hydrogen and Quercetin Release for Scar-Reduced Regeneration of Burn Wounds.
- 1Department of Burns, Tongren Hospital of Wuhan University (Wuhan Third Hospital), School of Pharmaceutical Sciences, Wuhan University, Wuhan, People's Republic of China.
- 2Key Laboratory of Advanced Pharmaceutics, School of Health, China Three Gorges University, Yichang, People's Republic of China.
- 3Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, People's Republic of China.
Abstract
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.
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BibTeX
@article{zeng2026phaseprogrammed,
title = {{Phase-Programmed Microneedles Enable Sequential Hydrogen and Quercetin Release for Scar-Reduced Regeneration of Burn Wounds.}},
author = {Yongnian Zeng and Zhigang Chu and Huiyuan Yang and Wen Zhang and Peng Jiang and Jiapeng Lei and Siyu Zhang and Qiongfang Ruan and Shuhua Liu and Wei Li},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78512},
url = {https://europepmc.org/article/MED/42949795},
note = {CC BY},
}
RIS
TY - JOUR
TI - Phase-Programmed Microneedles Enable Sequential Hydrogen and Quercetin Release for Scar-Reduced Regeneration of Burn Wounds.
AU - Yongnian Zeng
AU - Zhigang Chu
AU - Huiyuan Yang
AU - Wen Zhang
AU - Peng Jiang
AU - Jiapeng Lei
AU - Siyu Zhang
AU - Qiongfang Ruan
AU - Shuhua Liu
AU - Wei Li
PY - 2026
DA - 2026/10/28
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78512
UR - https://europepmc.org/article/MED/42949795
AB - 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.
SN - 2198-3844
ER -