Combining HUMSC Secretome and a Conductive Hydrogel Enhances Angiogenesis and Electrical Transmission at Myocardial Infarct Sites to Support Cardiac Repair

The postinfarction myocardium is in an environment of ischemia and hypoxia, and the damaged myocardium develops into scar tissue lacking electrical conductivity after a series of pathological changes. Thus, the regeneration of blood perfusion and electrical connections is crucial to repair the injured myocardium. In this study, an injectable self-doping conductive hydrogel composed of functionalized carboxymethyl chitosan (CMC) and oxidized hyaluronic acid (OHA) is developed for human umbilical cord mesenchymal stem cell (HUMSC)-derived secretome delivery to protect cardiac function after myocardial infarction (MI). In vitro experiments shows that the conductive hydrogel had good biocompatibility and conductivity consistent with the natural myocardium, and the secretome presents a good ability to promote cell proliferation, migration and angiogenesis. In a rat MI model, echocardiography shows an improvement in ejection fraction and fraction shortening after hydrogel injection. Additionally, susceptibility to arrhythmia is decreased in the standard clinically programmed electrical stimulation (PES) protocol. Immunofluorescence staining demonstrates that hydrogel treatment reduces cardiomyocyte apoptosis and oxidative stress, improves cardiomyocyte morphology and function, promotes angiogenesis. Overall, this study demonstrated the application potential of a conductive hydrogel combined with a cell-free strategy to reconstruct electromechanical coupling in infarcted myocardium and promote cardiac repair and regeneration.