In vitro microfluidic modelling of the human blood-brain-barrier microvasculature and testing of nanocarrier transport

Abstract

The blood-brain barrier (BBB) protects the brain from pathogens but also hinders drug delivery to the central nervous system. Most of the BBB models developed up to date failed to reproduce the human anatomical complexity of brain barriers, contributing to less predictive experimental platforms and poor patient outcomes. To overcome those limitations, the development of reliable in vitro models represents a crucial step towards more effective therapies. This contribution was focused on the development of an in vitro microfluidic model of the BBB able to replicate the human neurovascular organization. The microfluidic model included human induced pluripotent stem cell-derived endothelial cells, brain pericytes, and astrocytes as self-assembled microvascular networks in a 3-dimensional fibrin gel. As previously demonstrated, the BBB model exhibited perfusable and selective microvasculature, with permeability lower than conventional in vitro models and comparable with in vivo rat brain. Permeability of polystyrene nanoparticles (NPs) and synthesized polyurethane NP was measured across the BBB model as compared to conventional Transwell assays. This physiologically relevant BBB model offers an innovative and valuable platform to preclinically predict transport efficacy of drugs and carriers.