In Vitro Microfluidic Models for Neurodegenerative Disorders

Abstract

Microfluidic devices enable novel means of emulating neurodegenerative disease pathophysiology in vitro. These organ-on-a-chip systems can potentially reduce animal testing and substitute (or augment) simple 2D culture systems. Reconstituting critical features of neurodegenerative diseases in a biomimetic system using microfluidics can thereby accelerate drug discovery and improve our understanding of the mechanisms of several currently incurable diseases. This review describes latest advances in modeling neurodegenerative diseases in the central nervous system and the peripheral nervous system. First, this study summarizes fundamental advantages of microfluidic devices in the creation of compartmentalized cell culture microenvironments for the co-culture of neurons, glial cells, endothelial cells, and skeletal muscle cells and in their recapitulation of spatiotemporal chemical gradients and mechanical microenvironments. Then, this reviews neurodegenerative-disease-on-a-chip models focusing on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Finally, this study discusses about current drawbacks of these models and strategies that may overcome them. These organ-on-chip technologies can be useful to be the first line of testing line in drug development and toxicology studies, which can contribute significantly to minimize the phase of animal testing steps.

Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature

“…Changes in fluorescence intensity could be detected as far as 100 µm distance from the vessel wall (Figure 4c,d). In vivo, neurons are ≈10 to 20 µm from the brain capillaries, [ 61 ] implying that in a hypothetical in vitro BBB model incorporating neurons, [ 62 ] NPs can travel across the BBB and reach the target neurons.…”

Application of microfluidic systems for neural differentiation of cells

“…The microenvironmental advantages along with lower reagent consumption and costs are the reason for the welcoming of microfluidics in molecular and cellular biology research. However, we paid attention to neural differentiation of stem cells in this review, and microfluidics application's domain extends to various fields such as neurodegenerative disease models, [46] and cellular interactions. [47].…”

A low-cost, rapidly integrated debubbler (RID) module for microfluidic cell culture applications

“…Over the past two decades, these benefits have been extended to cell culture applications where favorable scaling effects (e.g. laminar flows, high surface to volume ratios, and short diffusion distances) have been leveraged to create physiologically-relevant microenvironments featuring precisely controlled biochemical and biophysical stimuli [3][4][5][6]. In these microscale systems, undisrupted flow is required to deliver cell culture media, maintain long-term cell viability, and control cellular-scale cues [7,8].…”