Neuroimmune-Metabolic Regulation by a Wireless Biodegradable Neuromodulator for Cardiovascular Therapy in a Mouse Model.

Abstract

Bioelectronic modulation of the vagus nerve offers a promising strategy for treating cardiovascular disease. Murine models that recapitulate neuroimmune-metabolic dysregulation are indispensable for preclinical neuromodulation research; however, the murine vagus nerve is extremely small, fragile, and difficult to interface with, making it challenging for existing devices to achieve the miniaturization, performance, and chronic biocompatibility required for long-term studies. Herein, we present a miniaturized, focused-ultrasound-driven, fully biodegradable vagus-nerve stimulator (UBVS) specifically engineered for murine application, enabling reliable and safe wireless neuromodulation. UBVS integrates a fully biodegradable triboelectric energy harvester and a self-adherent neural interface, achieving stable, suture-free chronic coupling without local neural injury. On-demand focused ultrasound provides spatiotemporally controlled, transcutaneous wireless power to the UBVS, allowing for precise stimulation of the cervical vagus nerve located in deep tissue. In a murine atherosclerosis model, chronic UBVS-mediated vagus nerve stimulation reprogrammed the neuroimmune-metabolic axis by suppressing inflammatory activation, enhancing autophagy-efferocytosis and remodeling lipid metabolism, thereby reducing plaque burden. These innovations achieve neurocompatible, long-term stimulation of delicate peripheral nerves, advancing wireless electroceutical therapies for cardiovascular and other chronic diseases.