A microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers.

Nat Commun

Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronics Interface, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1202, Geneva, Switzerland.

Published: October 2018

Peripheral nerves are anisotropic and heterogeneous neural tissues. Their complex physiology restricts realistic in vitro models, and high resolution and selective probing of axonal activity. Here, we present a nerve-on-a-chip platform that enables rapid extracellular recording and axonal tracking of action potentials collected from tens of myelinated fibers. The platform consists of microfabricated stimulation and recording microchannel electrode arrays. First, we identify conduction velocities of action potentials traveling through the microchannel and propose a robust data-sorting algorithm using velocity selective recording. We optimize channel geometry and electrode spacing to enhance the algorithm reliability. Second, we demonstrate selective heat-induced neuro-inhibition of peripheral nerve activity upon local illumination of a conjugated polymer (P3HT) blended with a fullerene derivative (PCBM) coated on the floor of the microchannel. We demonstrate the nerve-on-a-chip platform is a versatile tool to optimize the design of implantable peripheral nerve interfaces and test selective neuromodulation techniques ex vivo.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199302PMC
http://dx.doi.org/10.1038/s41467-018-06895-7DOI Listing

Publication Analysis

Top Keywords

nerve-on-a-chip platform
12
peripheral nerve
12
action potentials
8
microfabricated nerve-on-a-chip
4
platform
4
platform rapid
4
rapid assessment
4
assessment neural
4
neural conduction
4
conduction explanted
4

Similar Publications

Microphysiological systems (MPS) designed to study the complexities of the peripheral and central nervous systems have made marked improvements over the years and have allowed researchers to assess in two and three dimensions the functional interconnectivity of neuronal tissues. The recent generation of brain organoids has further propelled the field into the nascent recapitulation of structural, functional, and effective connectivities which are found within the native human nervous system. Herein, we will review advances in culture methodologies, focused especially on those of human tissues, which seek to bridge the gap from 2D cultures to hierarchical and defined 3D MPS with the end goal of developing a robust nervous system-on-a-chip platform.

View Article and Find Full Text PDF

Chemotherapy-induced peripheral neuropathy (CIPN) is a well-known, potentially permanent side effect of widely used antineoplastic agents. The mechanisms of neuropathic progression are poorly understood, and the need to test efficacy of novel interventions to treat CIPN continues to grow. Bioengineered microphysiological nerve tissue ("nerve on a chip") has been suggested as an in vitro platform for modeling the structure and physiology of in situ peripheral nerve tissue.

View Article and Find Full Text PDF

Organ-on-a-chip devices that mimic in vivo physiology have the potential to identify effects of chemical and drug exposure in early preclinical stages of drug development while relying less heavily on animal models. We have designed a hydrogel rat nerve-on-a-chip (RNoaC) construct that promotes axon growth analogous to mature nerve anatomy and is the first 3D in vitro model to collect electrophysiological and histomorphic metrics that are used to assess in vivo pathophysiology. Here we culture embryonic rat dorsal root ganglia (DRG) in the construct to demonstrate its potential as a preclinical assay for screening implications of nerve dysfunction in chemotherapy-induced peripheral neuropathy (CIPN).

View Article and Find Full Text PDF

Development of "organ-on-a-chip" systems for neuroscience applications are lagging due in part to the structural complexity of the nervous system and limited access of human neuronal & glial cells. In addition, rates for animal models in translating to human success are significantly lower for neurodegenerative diseases. Thus, a preclinical in vitro human cell-based model capable of providing critical clinical metrics such as nerve conduction velocity and histomorphometry are necessary to improve prediction and translation of in vitro data to successful clinical trials.

View Article and Find Full Text PDF

A microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers.

Nat Commun

October 2018

Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronics Interface, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1202, Geneva, Switzerland.

Peripheral nerves are anisotropic and heterogeneous neural tissues. Their complex physiology restricts realistic in vitro models, and high resolution and selective probing of axonal activity. Here, we present a nerve-on-a-chip platform that enables rapid extracellular recording and axonal tracking of action potentials collected from tens of myelinated fibers.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!