A Guided Approach to Establish a Functional Humanized Brain-on-a-Chip Microfluidic Model of the Neurovascular System

Methods in Cardiovascular and Lymphatic Biology. New York, NY: Springer US; 2025:35-52.

Establishing a functional humanized organ-on-a-chip microfluidic model of the neurovascular system is a cutting-edge approach in biomedical research. Such models can effectively mimic the human brain’s architecture and interactions with the vascular system, providing valuable insights for drug testing, disease modeling, and neurovascular disorders, significantly advancing our understanding of brain health and disease. This work covers several key components of establishing a functional brain-on-a-chip model to create a controlled environment that simulates the brain’s extracellular matrix and vasculature. These include incorporating various cell types, such as astrocytes, endothelial cells, pericytes, and immune cells, as well as the use of human-induced pluripotent stem cells (iPSCs) to derive these cell types, procedures to establish a functional multicultural system to study cell–cell interactions within the neurovascular unit, and methods to evaluate the model’s functionality through imaging techniques and biochemical assays. Creating a functional humanized brain-on-a-chip microfluidic model of the neurovascular system has the potential to support and greatly facilitate drug development processes and provide a more ethical alternative to animal testing.

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