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To address this, we developed a photocurable, hydrogel\u2010based cardiac patch (Gel\u2010CS\/FMN@LNP hydrogel) with favorable mechanical robustness. The patch is composed of methacryloylated carboxymethyl chitosan (CACSMA) and methacryloylated gelatin (GelMA), incorporating Formononetin\u2010loaded lipid nanoparticles (FMN@LNPs) for myocardial restoration. In vitro studies demonstrated that the Gel\u2010CS\/FMN@LNP hydrogel not only inhibited cardiomyocyte apoptosis by scavenging reactive oxygen species (ROS) but also promoted migration and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, when a co\u2010culture system of the Gel\u2010CS\/FMN@LNP hydrogel and heart\u2010forming organoids (HFOs) was subjected to oxygen\u2010glucose deprivation (OGD) conditions, the system effectively inhibited HFO apoptosis and suppressed HFO fibrosis. In vivo experiments in MI model rats revealed that the Gel\u2010CS\/FMN@LNP hydrogel group preserved a higher left ventricular ejection fraction (LVEF: 67.2 \u00b1 1.9%) compared to the MI group (LVEF: 41.7 \u00b1 4.7%) at 28 days post\u2010MI, thereby improving cardiac function. Histological analysis showed that the Gel\u2010CS\/FMN@LNP hydrogel reduced myocardial fibrosis in the infarct border zone, promoted angiogenesis, and facilitated macrophage polarization toward the M2 phenotype. RNA sequencing (RNA\u2010seq) identified pathways associated with metabolic regulation (PPAR signaling pathway), myocardial protection (PI3K\u2010Akt signaling pathway), anti\u2010fibrosis (inhibition of extracellular matrix remodeling), and anti\u2010inflammatory immune regulation (TNF signaling pathway). Single\u2010cell RNA sequencing (scRNA\u2010seq) revealed that the Gel\u2010CS\/FMN@LNP hydrogel promoted post\u2010MI cardiac repair through a multi\u2010target network involving circadian rhythm remodeling, matrix regulation, immune balance, and vascular protection. Our hydrogel system, which combines facile injectability, sustained release of active factors, and synergistic therapeutic effects, represents a promising therapeutic approach for post\u2010MI repair.<\/jats:p>","DOI":"10.1002\/adhm.71879","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:46:37Z","timestamp":1792647997000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Photocurable Hydrogel Cardiac Patch Incorporating Formononetin\u2010Loaded Lipid Nanoparticles for Myocardial Repair After Acute Ischemia"],"prefix":"10.1002","author":[{"given":"Jin","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Translational Medicine Putuo Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Translational Medicine Putuo Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Translational Medicine Putuo Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Kong","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Translational Medicine Putuo Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Dai","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Translational Medicine Putuo Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Translational Medicine Putuo Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Translational Medicine Putuo Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5963-2454","authenticated-orcid":false,"given":"Xiao","family":"Jin","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Translational Medicine Putuo Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Translational Medicine Putuo Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Qi","sequence":"additional","affiliation":[{"name":"Neocellmed Co. 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