Sprayable Nanozyme Hydrogel Epigenetically Reprograms Inflammation for Diabetic Wound Regeneration [GeoMX spatial transcriptomics]

Here we report a novel sprayable nanozyme hydrogel that epigenetically reprograms macrophages 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 excellent sprayability, conformal skin coverage, and long-term storage stability, offering substantial translatable potential. Notably, the nanozyme hydrogel induced distinct epigenetic modifications in macrophages by remodeling chromatin accessibility, effectively shifting gene expression from pro-inflammatory to anti-inflammatory profiles. This epigenetic modulation persisted under oxidative stress, actively suppressing inflammatory while facilitating regenerative responses.