Glucose/ROS-dual-responsive injectable hydrogel ameliorates myocardial infarction by restoring metabolic homeostasis in diabetic rats.

Injectable hydrogels capable of responding to pathological microenvironmental cues represent a promising therapeutic strategy for myocardial infarction (MI). However, existing systems that can simultaneously regulate metabolic abnormalities and drive multi-pathway for diabetic MI repair remain scarce. To address this, a glucose/reactive oxygen species (ROS)-dual responsive injectable hydrogel was developed with stimulus-responsive release properties and complementary multi-target therapeutic functions. The hydrogel exhibited favorable injectability and tissue adhesion, allowing stable retention at the injury site. In vitro studies demonstrated that the glucose-sensitive component enabled controlled puerarin release, while the ROS-sensitive segment showed nitric oxide (NO)-generating capability. When applied in vivo, the hydrogel system significantly reduced local ROS levels and promoted angiogenic responses in the infarcted myocardium. Importantly, the hydrogel improves cardiomyocyte energy supply and metabolic homeostasis by enhancing mitochondrial function and regulating glucose-lipid metabolic balance. Consequently, this combined approach significantly improved both vascular regeneration and myocardial repair in diabetic rats post-MI. This work provides a novel and effective strategy for the multifunctional treatment of diabetic myocardial injury and highlights the potential of smart responsive hydrogels in managing metabolic cardiovascular disorders.