<i>Salvia miltiorrhiza</i> ‐Derived Vesicle‐Like Nanoparticles Functionalised Hydrogel With Excellent Ability of Oxidative Stress Modulation and Anti‐Cardiomyocyte Apoptosis for Sepsis‐Induced Myocardial Injury

In the process of myocardial cell structural and functional damage caused by various factors, current therapeutic strategies primarily focus on restoring myocardial blood supply, often neglecting the inherent complex microenvironment triggered by elevated reactive oxygen species (ROS) levels during myocardial injury. Regulating mitochondrial function and inhibiting excessive ROS production to alleviate myocardial apoptosis are therefore critical for myocardial injury repair. Plant-derived vesicle-like nanoparticles have shown broad applications in multiple fields and possess potential value. In this context, the present study introduces Salvia miltiorrhiza-derived nanoparticles (SDVLNs) to counteract ROS effects after myocardial infarction. We performed in vitro experiments to analyse the effects of SDVLNs on cardiomyocyte proliferation, migration, oxidative stress, and mitochondrial function. Meanwhile, a novel concept of "natural plant-derived vesicle-like nanoparticles-gel" was proposed to address the stringent storage requirements of SDVLNs. We loaded SDVLNs into a thermo-sensitive hydrogel to prepare SDVLNs@hydrogel (SDVLNHs), and further conducted in vivo experiments to evaluate the therapeutic effects of locally administered SDVLNHs in lipopolysaccharide (LPS)-induced myocardial injury mice, with a focus on cardiac function and pathological changes in the heart. It was found that SDVLNs promoted cardiomyocyte proliferation and migration, alleviated oxidative stress, regulated mitochondrial function, and inhibited myocardial apoptosis. The developed SDVLNHs addressed the stringent storage requirements of SDVLNs, and local administration of SDVLNHs significantly improved cardiac function and reduced pathological damage in LPS-induced myocardial injury mice. Collectively, these findings highlight the potential of SDVLNs in myocardial injury repair and their applicability as a promising solution for myocardial injury in clinical settings.