Electrically rewired healing of the infarcted heart via a smart bioadhesive patch targeting fibrosis and calcium imbalance

In this study, an injectable conductive hydrogel (MeGG/PN@PP@G-8) based on a gellan gum/chitosan dual network (MeGG/PN) was designed and constructed. PEDOT: PSS imparts electrical coupling to the material, while the G-8 small molecule provides anti-inflammatory and anti-fibrotic activity. This system reduced ROS levels by 93.7% under H₂O₂-induced oxidative stress and increased the proportion of RAW264.7 macrophages toward the M2 phenotype by threefold, thereby shaping an immune microenvironment conducive to repair. In a rat myocardial infarction model, MeGG/PN@PP@G-8 patch treatment reduced IL-1β, IL-6, and TNF-α expressions by 96.1%, 95.3%, and 94.9%, respectively, nearly returning to sham group levels. Furthermore, treatment with the hydrogel reduced fibrosis area and enhanced angiogenesis and sarcomere remodeling. Transcriptome analysis further revealed that the material simultaneously inhibits pro-pathogenic pathways such as NF-κB/TNF and TGF-β/SMAD, while activating PI3K-Akt, ECM receptors, and angiogenic genes, achieving multi-pathway synergistic effects of anti-inflammatory, anti-fibrotic, pro-regenerative, and electrophysiological repair. The “wet adhesion-electrical coupling-drug synergy” strategy proposed in this study provides an innovative material platform and mechanistic basis for tissue regeneration and functional recovery after myocardial infarction.