Fabrication of Hydrogel Microchannels Using Aqueous Two-Phase Printing for 3D Blood Brain Barrier

Abstract

The blood-brain barrier (BBB) surrounds brain cells and prevents external substances from entering the brain through blood vessels. This complicates drug delivery to brain cells, but drugs that can cross the BBB have been developed recently, expanding the scope of treatment for brain diseases. However, traditional biological research typically relies on simple monolayer cell cultures that do not reflect the complex functional properties of human tissues and organs or their responses to external stimuli. Bioprinting technology is gradually overcoming the drawbacks of in vitro models by applying techniques, such as simulating 3D structures, which cannot be realized by biological models, utilizing biocompatible materials and mass cell culture at the tissue level; however, it has been limited to printing microstructural patterns. The in vitro model presented here printed the BBB microstructure in a liquid state, eliminating many defects inherent to printing on a flat surface in air. The aqueous two-phase printing (ATPP) material consisted of a composite matrix capable of phase separation, where three different cell types could be cultured to create a BBB model. The ATPP model will help in central nervous system disease research, drug screening, and drug discovery, because it provides an environment where the nutrient supply and drug concentration of cells can be controlled.