Multifunctional Polysaccharide Hydrogel Ameliorates Cardiac Function After Myocardial Infarction via Antioxidant, Immunomodulatory, and Pro-Angiogenic Activities

Myocardial infarction (MI) triggers excessive oxidative stress, a detrimental immune response, and insufficient angiogenesis, which collectively impede effective cardiac repair. This study developed a multifunctional composite polysaccharide hydrogel, termed KgXdgel, based on konjac glucomannan (KGM) and xanthan gum (XG) functionalized with gallic acid (GA) and dopamine (DA), respectively, to integrate reactive oxygen species (ROS) scavenging, macrophage polarization, and pro-angiogenic activities. In vitro assays demonstrated that the KgXdgel hydrogel exhibited excellent cytocompatibility, effectively scavenged ROS, promoted the polarization of macrophages towards the reparative M2 phenotype, and enhanced the migration and tube formation of human umbilical vein endothelial cells. In a rat MI model, treatment with KgXdgel significantly improved cardiac function (e.g., left ventricular ejection fraction, LVEF; left ventricular fractional shortening, LVFS), attenuated left ventricular dilation (LVIDs), and favorably modulated the post-infarction microenvironment. This was evidenced by the upregulation of the M2 marker CD163 and the angiogenic factor VEGF, alongside the downregulation of pro-inflammatory cytokines (e.g., IL-1β, TNF-α) and the M1 marker iNOS. These findings conclusively demonstrate that the KgXdgel hydrogel synergistically promotes cardiac repair post-MI through its integrated antioxidant, immunomodulatory, and pro-angiogenic functions, presenting a promising multi-targeted therapeutic strategy.