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.