Molecular Mechanisms of Myocardial Repair and Cardiac Function Improvement With Hydrogel‐Mediated Macrophage‐Derived Exosome Delivery

This study investigates how a multifunctional regulatory hydrogel loaded with macrophage-derived exosomes (MDEs) remodels the cardiac microenvironment, enhances cardiac function, and promotes myocardial repair in heart failure post-myocardial infarction. The hydrogel was prepared and characterized, and its effects on cardiomyocyte survival, proliferation, migration, and tube formation were evaluated using in vitro models. In vivo experiments on a mouse myocardial infarction model demonstrated improved cardiac function and decreased incidence of arrhythmias after treatment with the hydrogel. RNA sequencing and proteomics analyses highlighted the potential involvement of PI3K/Akt/mTOR, Hippo, TGF-β, HIF-1, and FoxO pathways; mechanistic causality remains to be established. The findings are consistent with enhanced cardiomyocyte activities, increased expression of key proteins such as HIF-1α and BNIP3, and remodeling of the myocardial microenvironment that may facilitate myocardial repair and functional recovery; these associations do not establish causality.