Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a computational model of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of upper-limb motoneuron recruitment with EES and characterize the selectivity of cervical interfaces. We show that lateral electrodes produce a segmental recruitment of arm motoneurons mediated by the direct activation of sensory afferents, and that muscle responses to EES are modulated during movement. Intraoperative recordings suggested similar properties in humans at rest. These modelling and experimental results can be applied for the development of neurotechnologies designed for the improvement of arm and hand control in humans with quadriplegia.

We thank Sim4Life by ZMT, www.zurichmedtech.com for their support. We thank Brian K. Kwon for critically reading the manuscript and his insightful suggestions.

The convergence of materials science, electronics, and biology, namely bioelectronic interfaces, leads novel and precise communication with biological tissue, particularly with the nervous system. However, the translation of lab‐based innovation toward clinical use calls for further advances in materials, manufacturing and characterization paradigms, and design rules. Herein, a translational framework engineered to accelerate the deployment of microfabricated interfaces for translational research is proposed and applied to the soft neurotechnology called electronic dura mater, e‐dura. Anatomy, implant function, and surgical procedure guide the system design. A high‐yield, silicone‐on‐silicon wafer process is developed to ensure reproducible characteristics of the electrodes. A biomimetic multimodal platform that replicates surgical insertion in an anatomy‐based model applies physiological movement, emulates therapeutic use of the electrodes, and enables advanced validation and rapid optimization in vitro of the implants. Functionality of scaled e‐dura is confirmed in nonhuman primates, where epidural neuromodulation of the spinal cord activates selective groups of muscles in the upper limbs with unmet precision. Performance stability is controlled over 6 weeks in vivo. The synergistic steps of design, fabrication, and biomimetic in vitro validation and in vivo evaluation in translational animal models are of general applicability and answer needs in multiple bioelectronic designs and medical technologies.