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Abstract Modulation of the peripheral nervous system (PNS) has a great potential for therapeutic intervention as well as restore bodily functions. Recent interest has focused on autonomic nerves, as they regulate extensive functions implicated in organ physiology, chronic disease state and appear tractable to targeted modulation of discrete nerve units. Therapeutic interventions based on specific bioelectronic neuromodulation depend on reliable neural interface to stimulate and record autonomic nerves. Furthermore, the function of stimulation and recording requires energy which should be delivered to the interface. Due to the physiological and anatomical challenges of autonomic nerves, various forms of this active neural interface need to be developed to achieve next generation of neural interface for bioelectronic medicine. In this article, we present an overview of the state-of-the-art for peripheral neural interface technology in relation to autonomic nerves. Also, we reveal the current status of wireless neural interface for peripheral nerve applications. Recent studies of a novel concept of self-sustainable neural interface without battery and electronic components are presented. Finally, the recent results of non-invasive stimulation such as ultrasound and magnetic stimulation are covered and the perspective of the future research direction is provided.

Abstract Peripheral nerve interfaces are a central technology in advancing bioelectronic medicines because these medical devices can record and modulate the activity of nerves that innervate visceral organs. Peripheral nerve interfaces that use electrical signals for recording or stimulation have advanced our collective understanding of the peripheral nervous system. Furthermore, devices such as cuff electrodes and multielectrode arrays of various form factors have been implanted in the peripheral nervous system of humans in several therapeutic contexts. Substantive advances have been made using devices composed of off-the-shelf commodity materials. However, there is also a demand for improved device performance including extended chronic reliability, enhanced biocompatibility, and increased bandwidth for recording and stimulation. These aspirational goals manifest as much needed improvements in device performance including: increasing mechanical compliance (reducing Young’s modulus and increasing extensibility); improving the barrier properties of encapsulation materials; reducing impedance and increasing the charge injection capacity of electrode materials; and increasing the spatial resolution of multielectrode arrays. These proposed improvements require new materials and novel microfabrication strategies. This mini-review highlights selected recent advances in flexible electronics for peripheral nerve interfaces. The foci of this mini-review include novel materials for flexible and stretchable substrates, non-conventional microfabrication techniques, strategies for improved device packaging, and materials to improve signal transduction across the tissue-electrode interface. Taken together, this article highlights challenges and opportunities in materials science and processing to improve the performance of peripheral nerve interfaces and advance bioelectronic medicine.