Ultrasound-driven electrical stimulation of peripheral nerves based on implantable piezoelectric thin film nanogenerators

Electrical stimulation of peripheral nerves is a powerful tool in neuroprosthesis and bioelectronic medicines to treat diverse clinical conditions. To achieve minimally invasive bioelectrical interfaces, the new generation of soft implantable neurostimulators with programmable electrical-stimulation functionality is highly demanded, but it remains a big challenge. Owing to the advantages of ultrasound in biomedical applications, such as deep tissue penetration and excellent clinical safety, we explore directly electrical stimulation of peripheral nerves with soft piezoelectric thin film nanogenerator which can be remotely driven by programmable ultrasound pulses. An ultrasound-active thin film nanogenerator with superior output performance was developed on basis of piezoelectric composite thin films containing 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 (BZT-BCT) nanowires and polyvinylidene fluoride (PVDF) polymer. The piezoelectric thin film nanogenerators without accessory rectifiers can directly serve as neurostimulators, and the electrical pulses generated by the implantable piezoelectric thin film nanogenerator can be programmed by remote ultrasound excitation with adjustable input power and waveform. With sciatic nerves of rats as a model, the directly electrical neurostimulation was successfully achieved by subcutaneously implanted piezoelectric thin film nanogenerators with thickness of around 30 mu m, and the stimuli controllability was systematically investigated with varied ultrasound parameters, including acoustic pressure, pulse width and pulse interval. Our ultrasound-driven electrical stimulation of peripheral nerves with ultrasound-active implantable thin film nanogenerators demonstrated a novel strategy to construct a programmable battery-free neurostimulator using soft and implantable energy devices which can be real-time-responsive to programmable external energy sources.