Blood-brain barrier spheroids and 3D-printed perfusable chips as in vitro screening platforms for brain-penetrating agents
Benjamin Scott ’20, Carlsbad, California
The blood-brain-barrier (BBB) is a major roadblock for therapeutic delivery to the central nervous system (CNS) in treating neuro-pathologies. In vitro models of the BBB are critical tools for the study of BBB transport mechanisms and development of drugs that can reach brain tissues. Current models of the BBB are proving more and more difficult and costly. Reproducibility of BBB properties and functions, in cultured brain endothelial cells, has proven to be challenging, and animal experiments are costly, laborious and could confer interspecies variations. The need for effective, functional, and cost effective BBB in vitro models is critical for the development and rapid testing of CNS therapeutics. BBB organoid spheroids and 3D-printed perfusable chips are two newly developed BBB models that create both optimal in vitro settings at a low cost. BBB organoids are spherical structures made up of human astrocytes at the core and human brain vascular pericytes and human brain endothelial cell outer layer. The grouping and ordering of cells constitutes a “blood-brain barrier” that displays physiological features in an in vitro setting. BBB organoid spheroids provide a route of analysis to measure a penetration agent’s ability to successfully cross the BBB. 3D-printed perfusable chips are created by a bio-printer that is capable of dispensing cells and hydrogel materials at a nanodrop level with micrometer accuracy. Collagen hydrogel is used as a scaffolding to build up the chip and create channels within the chip. The function of the collagen is to allow for cell growth within the chip and the channels are used to pump fresh nutrients into the chip, thus, creating a vascular like environment. The creation of a vascular BBB environment allows for study of therapeutic travel in the bloodstream. Results show how the development of both models is progressing and what features each model displays.