Microphysiological models of the central nervous system with fluid flow

Abstract

There are over 1,000 described neurological and neurodegenerative disorders affecting nearly 100 million Americans - roughly one third of the U.S. population. Collectively, treatment of neurological conditions is estimated to cost $800 billion every year. Lowering this societal burden will require developing better model systems in which to study these diverse disorders. Microphysiological systems are promising tools for modeling healthy and diseased neural tissues to study mechanisms and treatment of neuropathology. One major benefit of microphysiological systems is the ability to incorporate biophysical forces, namely the forces derived from biological fluid flow. Fluid flow in the central nervous system (CNS) is a complex but important element of physiology, and pathologies as diverse as traumatic or ischemic injury, cancer, neurodegenerative disease, and natural aging have all been found to alter flow pathways. In this review, we summarize recent advances in three-dimensional microphysiological systems for studying the biology and therapy of CNS disorders and highlight the ability and growing need to incorporate biological fluid flow in these miniaturized model systems.

Keywords: Bioprinting; Fluid flow; Hydrogel; Microfluidic; Microphysiological; Neural tissue; Organoid; Shear stress.