Human Nerve-on-a-Chip. Engineering 3D functional human peripheral nerve in vitro

Abstract

Development of "organ-on-a-chip" systems in the space of the nervous system is lagging because of lack of availability of human neuronal & glial cells and the structural complexity of the nervous system. Furthermore, a sizeable challenge in the drug development pipeline and an often-cited reason for failure in a vast number of clinical trials conducted for neuropathological ailments is the lack of translation from animal models. A preclinical in vitro model capable of mimicking the function and structure of the human nervous system is well desired. We present an in vitro biomimetic model of all-human peripheral nerve tissue capable of showing a robust neurite outgrowth (~5mm), myelination of human induced pluripotent stem cells (iPSCs)-derived neurons by primary human Schwann cells and evaluation of nerve conduction velocity (NCV), previously unrealized for any human cell-based in vitro system. This Human Nerve-on-a-chip (HNoaC) system is the first microphysiological system of human peripheral nerve which can be used for evaluating electrophysiological and histological metrics, which are gold-standard assessment techniques previously only possible with in vivo studies.