Injectable, Conductive, Multifunctional Hydrogels with Sustained Luteolin Release for Promoting Myocardial Infarction Repair

Myocardial infarction (MI) triggers a pathological cascade involving inflammation, oxidative stress, and electrophysiological dysfunction, collectively leading to adverse cardiac remodeling. To address these interconnected pathological challenges, we developed an injectable conductive hydrogel (FLCM). Constructed from a thermo-/photo-cross-linkable Pluronic F127 diacrylate matrix functionalized with luteolin, recombinant human collagen type I, and MXene nanosheets, FLCM exhibits excellent injectability, electrical conductivity, mechanical robustness, cell affinity, and sustained drug release capability. In a rat MI model, FLCM implantation effectively attenuated the inflammatory response by reducing pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) while promoting M2 macrophage polarization. Concurrently, it alleviated oxidative stress, preserved connexin 43 expression to enhance myocardial electrical coupling, and significantly lowered the incidence of ventricular arrhythmias. Through these synergistic actions, FLCM improved the infarct microenvironment, thereby suppressing excessive fibrosis, mitigating adverse cardiac remodeling, and restoring left ventricular function. Integrated transcriptomic profiling and protein-level validation revealed that FLCM synchronously modulated extracellular matrix reorganization and coordinated the regulation of the PI3K-Akt and NF-κB signaling pathways, while simultaneously activating the Nrf2/HO-1 antioxidant defense system. Therefore, this study presents an integrated hydrogel system that simultaneously targets multiple post-MI pathological processes, offering a translatable strategy for comprehensive cardiac repair and functional recovery.