Ultrasound activated selenium doped piezoelectric bioglass nanotherapy for protection against myocardial ischemia-reperfusion injury

The effective treatment and timely management of myocardial ischemia-reperfusion injury (MIRI) continue to pose significant challenges in cardiovascular therapy. This difficulty primarily arises from complex pathological processes involving oxidative stress, calcium overload, and cardiomyocyte apoptosis. Conventional pharmacological and mechanical interventions often involve invasive risks, potential side effects, limited mechanisms, and reduced effectiveness in the cardiac environment. In this study, we introduce a novel ultrasound (US)-activated piezoelectric therapy that electrically regulates calcium overload and delivers bioactive ions for antioxidant and myocardial regeneration through an injectable chitosan-glycine-selenium-doped bioglass (Cs-Gly-Se-BGS). This creates a sophisticated therapeutic platform that enables a synergistic approach with controlled electromechanical stimulation and ion release upon US activation. In vitro studies demonstrate that Cs-Gly-Se-BGS effectively maintains calcium homeostasis and scavenges reactive oxygen species (ROS) during episodes of oxygen-glucose deprivation followed by reoxygenation (OGD/R). Furthermore, this nanomedicine can repair damaged cells, enhance cell proliferation and migration, and promote vascularisation. In vivo experiments demonstrate that the US-triggered delivery of Cs-Gly-Se-BGS into the pericardial cavity of mice experiencing MIRI results in significant improvements in myocardial function, as evidenced by increases in ejection fraction (EF) and fractional shortening (FS). Histological analyses reveal a reduction in cardiac fibrosis and infarct size, along with improved formation of new blood vessels. Notably, its therapeutic effects even surpass those of the clinical drug Nifedipine. This study presents an innovative non-pharmacological strategy combining localized electrical stimulation, offering promising advantages for treating MIRI within cardiovascular medicine.