A Sr2+-Incorporated Polysaccharide Hydrogel Promotes Multifunctional Cardiac Repair after Myocardial Infarction

Abstract

Following myocardial infarction (MI), adverse ventricular remodeling driven by impaired angiogenesis, cardiomyocyte loss, and fibrosis leads to progressive cardiac dysfunction. Here, we developed a thermosensitive injectable Sr2+-loaded OSA–DTPH–agarose hydrogel (Sr@OSDA) constructed through dynamic Schiff-base crosslinking, agarose-mediated physical networking, and reversible Sr2+–carboxylate coordination interactions. The hydrogel exhibited favorable biocompatibility, mechanical properties comparable to native myocardium, and sustained local Sr2+ availability within the infarct microenvironment. Unlike conventional multicomponent strategies, Sr@OSDA employed Sr2+ as the primary bioactive cue while maintaining a simplified therapeutic design. In a rat MI model, Sr@OSDA significantly promoted angiogenesis, which was associated with the activation of the AKT/eNOS signaling pathway and enhanced CD31+ microvessel density and α-SMA+ arteriole formation. Moreover, Sr@OSDA enhanced reparative macrophage responses, modulated autophagic activity during the early stage after MI, and partially restored connexin 43 (Cx43) expression. These coordinated reparative responses contributed to improved myocardial repair and attenuated adverse ventricular remodeling after infarction. Collectively, Sr@OSDA provides a mechanically adaptive hydrogel platform with bioactive ion delivery capability for ischemic myocardial repair by harnessing the pleiotropic bioactivities of Sr2+.