A “drug-carrier homologation” cardiac patch for myocardial infarction therapy <i>via</i> month-long controlled H ₂ S release

Hydrogen sulfide (H₂S), a gaseous signaling molecule with multiple cardioprotective effects, has attracted considerable attention for treating myocardial infarction (MI), a leading global cause of death. However, its ultrashort half-life (seconds to minutes) and the extended recovery required for myocardial repair pose substantial challenges to therapeutic efficiency, emphasizing the urgent need for month-level controlled H₂S delivery strategies, an endeavor still unresolved. Inspired by natural trisulfide H₂S donors, we introduce a novel disulfide/trisulfide cross-linked network derived from natural lipoic acid (LA) and its trisulfide derivative LATS, engineered as a drug-carrier homologated cardiac patch (Fe@LA/LATS) for MI therapy. Fe@LA/LATS adheres firmly to wet cardiac tissue, providing a stable mechanical support while undergoing thiol-responsive depolymerization to release LA and H₂S. <i>In situ</i>-released LA scavenges reactive oxygen species (ROS) and attenuates the inflammatory response around the infarcted myocardium. Concurrently, H₂S significantly stimulates cardiomyocyte proliferation and angiogenesis, further accelerating myocardial regeneration and functional recovery. Impressively, Fe@LA/LATS containing 5% LATS ensures a controlled release of H₂S at therapeutically effective levels for 1 month, with a seamless release process until complete degradation. This new strategy dramatically enhances the overall therapeutic efficiency, exhibiting promising potential for further applications.