Adhesive nonfibrotic bioelectronic interfaces on diverse peripheral nerves for long-term functional neuromodulation

Bioelectronic devices implanted on peripheral nerves offer potential for the treatment and rehabilitation of clinical diseases. However, the foreign body reaction and the subsequent fibrous capsule formation at the device-peripheral nerve interface severely limit their efficacy and longevity in vivo. Here, we describe a robust bioadhesive strategy that can establish nonfibrotic bioelectronic interfaces on diverse peripheral nerves-occipital, vagus, deep peroneal, sciatic, tibial, and common peroneal nerves-for up to 12 weeks. Our approach inhibits the infiltration of immune cells into the interface, thereby preventing the formation of fibrous capsules in the inflammatory microenvironment. We demonstrate that our adhesive bioelectronic device with nonfibrotic interfaces maintains long-term blood pressure regulation in a spontaneously hypertensive rat model over 4 weeks. Furthermore, we confirm minimal accumulation of macrophages, smooth muscle actin, and collagen at nonfibrotic bioelectronic interfaces after 12 weeks of device implantation with nerve stimulation, supporting long-lasting neuromodulation without fibrosis.