An autophagy-modulating strontium-delivery hydrogel for post-myocardial infarction angiogenesis and myocardial repair

Cardiomyocyte apoptosis and vascular dysfunction after myocardial infarction are major drivers of heart failure progression. In this study, we systematically evaluated the synergistic effects of an engineered hydrogel incorporating decellularized cardiac extracellular matrix (dECM) and SrSiO₃ on myocardial repair through multiple mechanisms. By combining dECM with gelatin methacryloyl (GelMA) and hyaluronic acid methacrylate (HAMA), we developed a photosensitive hydrogel with enhanced biocompatibility and mechanical properties. Following UV polymerization, the hydrogel exhibited controlled degradation and sustained Sr²⁺ release over 28 days. Functionally, released Sr²⁺ promoted endothelial angiogenesis and regulated autophagic homeostasis via the p-mTOR pathway, thereby reducing hypoxia-induced cardiomyocyte apoptosis. In vivo, the Sr²⁺-containing hydrogel significantly improved cardiac function and reduced myocardial fibrosis in infarcted mice. Human cardiac organoid studies further confirmed the autophagy-regulating mechanism of Sr²⁺. Overall, this work presents a promising myocardial repair strategy based on the synergistic effects of angiogenesis promotion, apoptosis inhibition, and autophagy regulation.