Advances in Blood-Brain Barrier-on-a-Chip Models for Neurological Research and Therapeutics

The blood-brain barrier (BBB) is a selectively permeable gate between the brain and the central nervous system. It is essential in preserving brain function, as it protects the brain from harmful substances while permitting necessary nutrients. Traditional in vitro and in vivo models have provided fundamental insights into BBB physiology and pathology, yet they often fall short in mimicking the dynamic, multicellular, and mechanical microenvironment of the human BBB. The development of blood-brain barrier-on-a-chip (BBB-oC) platforms represents a significant degree of progress within biomedical engineering and neurobiology, leading to more physiologically relevant modeling of the neurovascular unit. These microfluidic systems utilize humanderived endothelial cells, astrocytes, pericytes, and shear flow to simulate the BBB’s structure and function with unprecedented fidelity. This study provides a comprehensive analysis of recent developments in BBB-on-a-chip (BBB-oC) technologies, focusing on novel developments in microfluidic design, materials, cellular integration, and real-time monitoring techniques. Special significance is placed on the use of these platforms to model neurodegenerative diseases, particularly Alzheimer’s disease, which is characterized by early and progressive BBB dysfunction. BBB-oC systems offer encouraging new avenues for drug screening, mechanistic studies, and personalized medicine applications. Current limitations, such as scalability, cost, and integration with systemic circulation models are addressed, and emerging solutions driven by artificial intelligence, organoid fusion, and high throughput screening technologies are discussed. By bridging neuroscience, engineering, and disease modeling, BBB-oC platforms represent a powerful tool for translational research and precision therapeutics. This study consolidates key findings, identifies knowledge gaps, and outlines directions for future development in the field.