Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Microfluidics for Brain Endothelial-Astrocytic Interactions

Version 1 : Received: 13 June 2023 / Approved: 15 June 2023 / Online: 16 June 2023 (03:39:04 CEST)

How to cite: Sanapathi, J.; Vipparthi, P.; Sosnik, A.; Kumarasamy, M. Microfluidics for Brain Endothelial-Astrocytic Interactions. Preprints 2023, 2023061121. https://doi.org/10.20944/preprints202306.1121.v1 Sanapathi, J.; Vipparthi, P.; Sosnik, A.; Kumarasamy, M. Microfluidics for Brain Endothelial-Astrocytic Interactions. Preprints 2023, 2023061121. https://doi.org/10.20944/preprints202306.1121.v1

Abstract

With the approval of the 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 use these models to assess the efficacy of novel therapies. These thumb-sized organ-on-a-chip systems have the potential to reduce animal testing and replace simple 2D culture systems. 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. 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. Recent advances in modeling cell-to-cell communication in the CNS are described in this review. 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 recapitulation of spatiotemporal biophysicochemical gradients and mechanical microenvironments. Brain endothelial cell-astroglia-on-a-chip models with a focus on neurodegenerative diseases such Alzheimer's disease, Parkinson's disease, and Huntington's disease and amyotrophic lateral sclerosis is introduced. Then, the current limitations of these microfluidic devices and strategies to overcome them are discussed.

Keywords

astroglia; endothelial cells; biomimetic systems; microfluidics; neurodegeneration

Subject

Biology and Life Sciences, Neuroscience and Neurology

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