An implantable biohybrid nerve model towards synaptic deep brain stimulation

Abstract

AbstractRestoring functional vision in blind patients lacking a healthy optic nerve requires bypassing retinal circuits, ideally, by directly stimulating the visual thalamus. However, available deep brain stimulation electrodes do not provide the resolution required for vision restoration. We developed an implantable biohybrid nerve model designed for synaptic stimulation of deep brain targets. The interface combines a stretchable stimulation array with an aligned microfluidic axon guidance system seeded with neural spheroids to facilitate the development of a 3 mm long nerve-like structure. A bioresorbable hydrogel nerve conduit was used as a bridge between the tissue and the biohybrid implant. We demonstrated stimulation of spheroids within the biohybrid structurein vitroand used high-density CMOS microelectrode arrays to show faithful activity conduction across the device. Finally, implantation of the biohybrid nerve onto the mouse cortex showed that neural spheroids grow axonsin vivoand remain functionally active for more than 22 days post-implantation.