Pericytes-Assisted Vascular Lumen Organization in a Novel Dynamic Human Blood-Brain Barrier-on-Chip Model

Organ-on-Chips (OoCs) are pivotal in neurovascular research, particularly for modeling the blood-brain barrier (BBB), due to their ability to replicate the complex architecture and dynamics of the blood flow in the BBB. This study introduces an innovative microfluidic device that enhances BBB modeling by incorporating human endothelial cells (ECs), pericytes, and astrocytes. The study provides critical insights into the alignment and organization of actin filaments in brain ECs under flow and the role of pericytes and astrocytes in vascular lumen stability. The microfluidic device features both "open" and "enclosed" versions, catering to static and dynamic flow conditions. Findings reveal that the presence of pericytes is essential for the structural organization of the endothelial lumen and its stability under dynamic conditions. Permeability assays and TEER measurements indicate that the model’s permeability values closely match those observed in vivo. This human BBB-on-chip model offers a robust platform for studying the interactions among neurovascular components and has significant potential for drug screening and therapeutic research for central nervous system diseases