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

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.

Automated summary

The complexity of the human brain poses significant challenges for neurological drug development, but advanced in vitro Brain-on-a-Chip platforms are increasingly enabling researchers to overcome these hurdles. These platforms mimic key features of the brain and provide meaningful added value over conventional cell culture systems by recreating the brain's microenvironment and including critical components like the blood-brain barrier. The future direction of these technologies is to continuously improve model fidelity and depth of research.