Recent advances in blood-brain barrier-on-a-chip models

The blood-brain barrier is a physiological barrier between the vascular system and the nervous system. Under healthy conditions, it restricts the passage of most biomolecules into the brain, making drug development exceedingly challenging. Conventional cell-based in vitro models provide valuable insights into certain features of the BBB. Nevertheless, these models often lack the three-dimensional structure and dynamic interactions of the surrounding microenvironment, which greatly influence cell functionality. Consequently, considerable efforts have been made to enhance in vitro models for drug development and disease research. Recently, microfluidic organ-on-a-chip systems have emerged as promising candidates to better mimic the dynamic nature of the BBB. This review provides a comprehensive overview of recent BBB-on-chip devices. The typical building blocks, chip designs, the perfusion infrastructure, and readouts used to characterize and evaluate BBB formation are presented, analyzed, and discussed in detail. Statement of Significance: The blood-brain barrier (BBB) is a highly selective barrier that controls what can enter the brain. While it protects the brain from harmful substances, it also hinders the delivery of treatments for neurological diseases such as Alzheimer's and Parkinson's. Due to its complexity, studying the BBB in living organisms remains difficult. However, recent advances in "organ-on-a-chip" technology have allowed scientists to create small, engineered models that replicate the BBB. These models provide a powerful platform to study diseases and test potential drugs with greater accuracy than traditional methods. Organ-on-a-chip devices are designed to mimic the behavior of organs or tissues in the human body, offering a more realistic and controlled environment for research. This review highlights recent breakthroughs in BBB-on-a-chip technology, showing how these models enhance current research and have the potential to transform the way we study brain diseases and develop new drugs. By integrating biology and engineering, BBB-on-a-chip technology has the potential to transform neuroscience research, improve drug development, and enhance our understanding of brain disorders.