Hybrid nanogenerator based closed-loop self-powered low-level vagus nerve stimulation system for atrial fibrillation treatment

Abstract

Atrial fibrillation is an "invisible killer" of human health. It often induces high-risk diseases, such as myocardial infarction, stroke, and heart failure. Fortunately, atrial fibrillation can be diagnosed and treated early. Low-level vagus nerve stimulation (LL-VNS) is a promising therapeutic method for atrial fibrillation. However, some fundamental challenges still need to be overcome in terms of flexibility, miniaturization, and long-term service of bioelectric stimulation devices. Here, we designed a closed-loop self-powered LL-VNS system that can monitor the patient's pulse wave status in real time and conduct stimulation impulses automatically during the development of atrial fibrillation. The implant is a hybrid nanogenerator (H-NG), which is flexible, light weight, and simple, even without electronic circuits, components, and batteries. The maximum output of the H-NG was 14.8 V and 17.8 μA (peak to peak). In the in vivo effect verification study, the atrial fibrillation duration significantly decreased by 90% after LL-VNS therapy, and myocardial fibrosis and atrial connexin levels were effectively improved. Notably, the anti-inflammatory effect triggered by mediating the NF-κB and AP-1 pathways in our therapeutic system is observed. Overall, this implantable bioelectronic device is expected to be used for self-powerability, intelligentization, portability for management, and therapy of chronic diseases.

Keywords: Atrial fibrillation; Closed-loop control; Implantable electronics; Low-level vagus nerve stimulation; Nanogenerators; Self-power.