Fig. 2

Evolution in creating in vitro BBB models. A. Model of the static BBB shows no fluid flow. i. The first generation of in vitro BBB models used a static endothelium monolayer separated by a porous membrane from co-culture pericytes and astrocytes called the transwell platform. ii. Microfluidics horizontal models with two main channels coupled by several migration channels enable the creation of a 3D ECs monolayer in a single compartment. iii. 3D NVU spheroid development in 96 well-plates. iv. The construction of three-dimensional lumen structures using 3D bioprinting methods. B. Model of the dynamic BBB allowing continuous flow generation in culture by a pumping device. i. Two-layer (vertical) designs similar to the transwell system, including ECs may form 2D or 3D EC monolayers in one compartment. At the same time, other cell types are cultured in a porous membrane-separated compartment. ii. A one-layer platform including a horizontal phage-based platform that utilizes the surface tension of ECM materials to separate 3D endothelial and other neurovascular unit cells. iii. A network model of the microvasculature using angiogenesis or vasculogenesis features may simulate the brain microvessel network on-a-chip. ECs represents endothelial cells; PC, pericytes; ACs, astrocytes