Microfluidics for brain endothelial cell-astrocyte interactions

With the approval of the Food and Drug (FDA) Modernization Act 2.0, the pharmaceutical industry is poised to expand its research components with a plethora of alternative models, including organ-on-microfluidic chips in pharma and biotechnology, resulting in a personalized approach. Microfluidics opens new possibilities for the study of cell biology, especially for a better understanding of cell-cell interactions and the pathophysiology of neurodegenerative diseases in vitro, and the use of these models to assess the efficacy of novel therapies is promising. These thumb-sized organ-on-a-chip systems have the potential to reduce animal testing and replace simple 2D culture systems that do not succeed to resemble the complex physiology of tissues and organs. Restoring critical aspects of endothelial-brain immune cell communication in a biomimetic system using microfluidics may accelerate the process of central nervous system (CNS) drug discovery and improve our understanding of the mechanisms of multiple neurodegenerative diseases. In addition, these organ-on-chip technologies can be used to optimize drug targets and assess drug efficacy and toxicity in real-time, which can significantly help minimize animal testing requirements, as authorized by the recent FDA Act. This Review initially summarizes the fundamental advantages of microfluidic systems in creating a compartmentalized cell culture for the complex three-dimensional architectures of neural tissue cells such as neurons, glial cells, and endothelial cells, and their ability to recapitulate the spatiotemporal biophysicochemical gradients and mechanical microenvironments. Then, brain endothelial cell-astroglia-on-a-chip models with a focus on neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis are introduced. Finally, the current limitations of these microfluidic devices and strategies to overcome them are discussed.