Wireless electrical stimulation of the vagus nerves by ultrasound-responsive programmable hydrogel nanogenerators for anti-inflammatory therapy in sepsis

Electroceuticals based on electrical stimulation of the vagus nerves shows great promise for therapeutic application in a variety of diseases and clinical conditions. The exploration of new generation neurostimulators with programmable, battery-free, and minimally invasive features is an emerging research field. Herein, we present wireless-powered battery-free vagus nerves stimulators based on implantable high-performance hydrogel nanogenerators (HENG) which can be driven by programmable ultrasound pluses remotely, and demonstrate the successful application of HENG in vagus nerves stimulation for the anti-inflammatory therapy in sepsis. The HENG is developed on the basis of polyacrylamide/graphene conductive hydrogels as a new kind of liquid-based triboelectric nanogenerators. With the device size of 1.5 cm x 1.5 cm x 1 mm and the ultrasound power density of 0.3 W/cm2, the short-circuit current generated by the HENG is measured to be 1.6 mA, which is comparable to the output current of commercial bulky neurostimulators. With the systemic inflammatory produced by endotoxin as a model, the alternating current pulse stimulation of the vagus nerves by the ultrasound-responsive HENG shows great effectiveness in the inhibition of pro-inflammatory cytokines. This work provides a novel strategy for the development of implantable soft high-performance nanogenerators as programmable battery-free neurostimulators for wireless electrical stimulation of the nerve systems.