Abstract
Chronic diabetic wounds represent a major clinical challenge, compounded by persistent inflammation, microbial invasion, and deficient angiogenesis. To address these intertwined pathophysiological features, we developed a copper-ion coordinated andrographolide-loaded hydrogel (ASFH), significantly enhancing andrographolide solubility and promoting wound healing dynamics. In vitro assessments demonstrated superior antimicrobial activity, optimal mechanical strength, self-healing ability, and cytocompatibility. In diabetic mice, ASFH notably accelerated wound closure, stimulated collagen maturation and re-epithelialization, dynamically shifted macrophages toward an anti-inflammatory phenotype, and markedly enhanced angiogenesis. Mechanistic studies integrating network pharmacology, molecular docking, dynamics simulations, and SPR validation pinpointed the Rac1/JNK1/Jun/Fos signaling cascade as a primary mediator of these regenerative effects. This work presents ASFH as a translationally relevant dressing system, simultaneously addressing critical limitations in diabetic wound management through targeted molecular therapeutic intervention.
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Data availability
All data are available in the main text or the supplementary materials. The raw datasets used and/or analyzed during the current study are available from the corresponding author.
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Acknowledgements
This study was funded by the National Natural Science Foundation of China (82460792, 82160770), the Zunyi Science and Technology Talent Platform Carrier Construction Project (ZSKRPT2023-1), the Department of Science and Technology of Guizhou Province (QKHPTRC-CXTD [2023] 024), the Guizhou Key Laboratory of Modern Traditional Chinese Medicine Creation (Qian Ke He Platform ZSYS [2025] 019), and the Zunyi City Municipal and University Joint Science and Technology Funding Project (Zunshi Kehe HZ [2025]251). The funder played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.
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Penghui Ye—original draft, methodology, investigation, formal analysis, and data curation. Yuhe Dai and Qianbo Zhang—investigation and data curation. Junqi Yang, Lele Liu, and Xiuying Guo—software, Formal analysis, and data curation. Rifang Gu, Ming Tang, Min Tan, Huan Zhu, Jitao Chen, and Felicity Han—Writing—review and editing. Xuqiang Nie—Writing—review and editing, supervision, conceptualization, project administration, and funding acquisition.
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Ye, P., Dai, Y., Zhang, Q. et al. Novel copper-ion coordinated andrographolide-loaded hydrogel activates Rac1/JNK1 axis for enhancing diabetic wound healing. npj Regen Med (2026). https://doi.org/10.1038/s41536-026-00457-y
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DOI: https://doi.org/10.1038/s41536-026-00457-y
