Ultrasound-driven piezoelectret-based nanogenerator stimulates vagus nerve for myocardial infarction treatment

Myocardial infarction (MI) stands as the predominant cause of morbidity and mortality within the spectrum of cardiovascular diseases, with an unfavorable long-term prognosis. Vagus nerve stimulation (VNS) emerges as a potential clinically significant intervention for alleviating myocardial remodeling after MI, offering promise as a therapeutic approach. However, challenges persist in addressing the fundamental issues of flexibility, miniaturization, and the long-term use of VNS devices. Here, we devised an implantable ultrasound-driven piezoelectret-based nanogenerator (UPN) as a wireless-powered and battery-free vagus nerve stimulator. The UPN with the features of flexibility and lightweight exhibited a maximum output of 10.68 V and 261 μA (peak to peak) under an ultrasonic probe setup at 700 mW cm−2. In the in vivo efficacy study, VNS therapy resulted in a notable improvement in cardiac function with the treatment of UPN, a 20.42 % enhancement in left ventricular ejection fraction and an 11.76 % increase in fractional shortening on the 28th day were realized. Concomitantly, inflammatory responses, myocardial fibrosis, and sympathetic nerve remodeling witnessed a significant reduction. Particularly noteworthy is the observed therapeutic effect linked to the inhibition of the IL-17 and TNF signaling pathways. In summary, this study introduces a novel strategy for nerve stimulation, offering a potential avenue for treating chronic inflammatory diseases.