Brain-on-a-Chip: Characterizing the next generation of advanced in vitro platforms for modeling the central nervous system

Abstract

The complexity of the human brain creates significant, almost insurmountable challenges for neurological drug development. Advanced in vitro platforms are increasingly enabling researchers to overcome these challenges, by mimicking key features of the brain's composition and functionality. Many of these platforms are called “Brains-on-a-Chip”—a term that was originally used to refer to microfluidics-based systems containing miniature engineered tissues, but that has since expanded to describe a vast range of in vitro central nervous system (CNS) modeling approaches. This Perspective seeks to refine the definition of a Brain-on-a-Chip for the next generation of in vitro platforms, identifying criteria that determine which systems should qualify. These criteria reflect the extent to which a given platform overcomes the challenges unique to in vitro CNS modeling (e.g., recapitulation of the brain's microenvironment; inclusion of critical subunits, such as the blood–brain barrier) and thereby provides meaningful added value over conventional cell culture systems. The paper further outlines practical considerations for the development and implementation of Brain-on-a-Chip platforms and concludes with a vision for where these technologies may be heading.

Organs-on-Chips Platforms Are Everywhere: A Zoom on Biomedical Investigation

“…Such revolutionary technology has widely impacted the research field, especially in areas such drug screening [ 159 ], disease modeling [ 160 ], cancer cell migration [ 161 , 162 ], axon growth [ 163 ], neuronal models [ 164 , 165 ], single-cell analysis [ 166 ], cell–cell interaction and cell-ECM studies [ 167 ], cell co-cultures [ 168 ], and even fluid gradient-involving studies such as bacterial chemotaxis [ 169 ]. Herein, we discuss the presence of such cutting-edge technology in nearly all the fields of scientific research and pre-clinical investigations.…”

Pathogens infecting the central nervous system

“…The simplest but most widely used in vitro BBB model is a transwell system containing a monolayer of human BMECs with or without astrocytes [ 32 ]. Microfluidic devices have recently been developed to better reflect complex three-dimensional BBB structures [ 33 ]. Most recently, the human neurovascular unit (hNVU) chip, which contains all the necessary cellular and extracellular brain components, was used to examine the neurotropism and BBB penetration of C .…”

Neuronal and glial cell co-culture organization and impedance spectroscopy on nanocolumnar TiN films for lab-on-a-chip devices

“…11 Great efforts have been made in recent years to bridge the gap between in vivo animal experiments and in vitro cell cultures, resulting in promising advances in biomimetic neural micro-environments, which mimic neural networks or structures found in the brain. 12,13 Such systems can offer great potential to study neural function, leading to the widespread field of brain-on-a-chip devices as, e.g., illustrated by Brofiga et al, 14 Maoz, 15 and Bang et al 16 However, the idea to recreate organs on chips does not end with brains, but rather extends to other organs such as lung, 17 liver, 18 kidney, 19 heart, 20 bone, 21 skin, 22 and many more. Thus, such organ-on-a-chip devices recapitulate the key features of the physiology of human organs.…”

“…12,13 Such systems can offer great potential to study neural function, leading to the widespread field of brain-on-a-chip devices as, e.g. , illustrated by Brofiga et al , 14 Maoz, 15 and Bang et al 16 However, the idea to recreate organs on chips does not end with brains, but rather extends to other organs such as lung, 17 liver, 18 kidney, 19 heart, 20 bone, 21 skin, 22 and many more. Thus, such organ-on-a-chip devices recapitulate the key features of the physiology of human organs.…”