A Whole‐Course‐Repair System Based on Stimulus‐Responsive Multifunctional Hydrogels for Myocardial Tissue Regeneration

Abstract Myocardial infarction (MI) has emerged as the predominant cause of cardiovascular morbidity globally. The pathogenesis of MI unfolds as a progressive process encompassing three pivotal phases: inflammation, proliferation, and remodeling. Smart stimulus‐responsive hydrogels have garnered considerable attention for their capacity to deliver therapeutic drugs precisely and controllably at the MI site. Here, a smart stimulus‐responsive hydrogel with a dual‐crosslinked network structure is designed, which enables the precise and controlled release of therapeutic drugs in different pathological stages for the treatment of MI. The hydrogel can rapidly release curcumin (Cur) in the inflammatory phase of MI to exert anti‐apoptotic/anti‐inflammatory effects. Recombinant humanized collagen type III (rhCol III) is loaded in the hydrogel and released as the hydrogel swelled/degraded during the proliferative phase to promote neovascularization. RepSox (a selective TGF‐β inhibitor) releases from Pluronic F‐127 grafted with aldehyde nanoparticles (PF127‐CHO@RepSox NPs) in the remodeling phase to against fibrosis. The results in vitro and in vivo suggest that the hydrogel improves cardiac function and alleviates cardiac remodeling by suppressing inflammation and apoptosis, promoting neovascularization, and inhibiting myocardial fibrosis. A whole‐course‐repair system, leveraging stimulus‐responsive multifunctional hydrogels, demonstrates notable effectiveness in enhancing post‐MI cardiac function and facilitating the restoration of damaged myocardial tissue.