Toward Natural Limb Function: A New Era in Prosthetic Innovation

The past decade has witnessed groundbreaking clinical implementation of neuroprosthetic limbs driven by signals from peripheral targets (eg, nerves and muscle) and the brain to restore limb function for individuals with limb loss or impairment. In this review, we highlight recent key clinical trials in peripheral neuroprosthetic interfaces directly with nerve, residual muscle, and reinnervated muscle. We then highlight the key advances in brain interfaces, including clinical trials using electroencephalography, electrocorticography, and intracortical electrodes to control neuroprosthetics. Finally, we explore the future of neuroprosthetic control where both peripheral and brain interfaces can be combined to improve neuroprosthetic performance. ANN NEUROL 2025;98:913-928.