(631f) A Multi-Cellular Brain-on-Chip with Integrated Vasculature

Our understanding of brain function under healthy and diseased states is dependent upon, and often limited by, the models and tools with which we study them. Previously, our group has developed an in vitro blood-brain barrier model derived from human induced pluripotent stem cells (iPSCs). We have expanded this system to a multi-cellular integrated brain (miBrain) composed of all major brain cell types derived separately from iPSCs (neurons, endothelial cells, pericytes, astrocytes, oligodendrocytes, and microglia) encapsulated together in an engineered hydrogel. These three-dimensional brain-tissue models are uniquely suited to study complex cellular interactions and emergent tissue behaviors.

Herein, we present our efforts toward engineering a fully vascularized miBrain platform in which iPSC-derived endothelial cells self-assemble to form brain microvasculature. We compare the miBrain co-culture system to brain microvascular endothelial cell (BMEC) monocultures in terms of morphological features and expression levels of key junction markers. We further investigate vascularization of the miBrain when adapted to a different form factor, microfluidic devices, that will ultimately enable rapid functional readouts and nutrient delivery via perfusable flow to support longer term culture periods. Finally, we explore the ability of this system to model nanoparticle-based delivery in the human brain microenvironment.