Current animal and in vitro cell-based models for studying brain-related pathologies and drug evaluation have limitations in reproducing the human blood-brain barrier's (BBB) architecture and physiology. This often leads to preclinical drug candidates failing in clinical trials due to poor BBB penetration. This review examines recent advances in organ-on-chip (OOC) BBB models, focusing on their potential to predict drug permeability. It highlights achievements and challenges in creating more biomimetic in vitro models using OOC technology, specifying the minimum requirements (cellular types, fluid flow, and tissue architecture) for a solid alternative to traditional in vitro models or animal models.

Inés Mármol, Sara Abizanda-Campo, Jose M Ayuso, Ignacio Ochoa, Sara Oliván