Abstract
Chronic diabetic wounds present a critical clinical challenge due to persistent inflammation and compromised healing. Here, we report a sprayable nanozyme hydrogel that epigenetically remodels macrophages (Mφ) to suppress inflammation and coordinate regeneration. Ultrasmall copper-based nanozymes (CuNZ, ~4 nm) synthesized via an eco-friendly one-pot method demonstrated potent multi-radical scavenging activity. When integrated into gelatin methacryloyl (Gel), CuNZ@Gel exhibited sprayability, conformal skin coverage, and storage stability, offering potential for clinical translation. Notably, the nanozyme hydrogel induced distinct epigenetic modifications in Mφ by remodeling chromatin accessibility, thereby shifting gene expression from a pro-inflammatory to an anti-inflammatory profile. This epigenetic modulation sustained under oxidative stress, actively suppressing inflammation while facilitating regenerative responses. In rat diabetic wound models, CuNZ@Gel significantly accelerated healing through its coordinated antioxidant, anti-inflammatory, and pro-regenerative actions. Unlike conventional passive dressings, this sprayable nanozyme hydrogel proactively remodels the wound microenvironment via epigenetic control of inflammation, providing a promising therapeutic strategy for managing chronic diabetic wounds and inflammatory skin complications.
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Acknowledgements
The authors acknowledge Ebiogen Inc. (Seoul, Republic of Korea) for transcriptome analysis. The authors thank the Dankook University Industry—Academic Cooperation Foundation Shared Equipment Facility (Cheonan, Republic of Korea), the National Center for Inter-University Research Facilities (NCIRF) at Seoul National University (Seoul, Republic of Korea), and the Kongju National University Joint Laboratory and Practical Training Center (Cheonan, Republic of Korea) for support with material characterization. The authors thank Suparna Bhattacharya (Institute of Tissue Regeneration Engineering) for assistance with the HAT activity assay. The authors acknowledge members of the Institute of Tissue Regeneration Engineering for their critical comments and suggestions on this work.
Funding
This work was supported by the National Research Foundation of Korea (NRF) under grant numbers RS-2025-25408965 and RS-2023-00247485 (to R.K.S.); RS-2024-00334160 and RS-2025-00515296 (to J.H.L.); RS-2021-NR060095, RS-2023-00220408, and RS-2024-00348908 (to H.W.K.). This work was also supported by the research fund from Dankook University in 2025 (Dankook Pioneer Research Fund to H.W.K. and J.H.L.).
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Kurian, A.G., Park, JH., Karunasagara, S. et al. Sprayable nanozyme hydrogel epigenetically remodels inflammation for diabetic wound regeneration. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72968-7
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DOI: https://doi.org/10.1038/s41467-026-72968-7
