Multicellular Self-Assembly of a 3D Bioprinted Cerebral Blood Vessel Model for Studying Cerebrovascular Inflammation in vitro

Abstract

Neurodegenerative diseases have affected the health and quality of life. One of the main causes of neurodegenerative diseases is known to be an abnormality in the regulation of the inflammatory response in the brain. The principal regulator of inflammatory responses in neurodegenerative diseases is the cerebral blood vessel that controls the molecular transport from the blood to the central nervous system. Since the cerebral blood vessel has sophisticated 3D architecture, it is necessary to recapitulate the tubular shape and tissue-specific intrinsic function in vitro. Here, we developed a 3D self-assembled tubular, free-standing human cerebral blood vessel model. First, we optimized bioink composition by using brain- and blood vessel-derived decellularized extracellular matrix bioinks. We optimized a co-axial cell printing process for fabricating a self-assembled cerebral blood vessel model with a layered structure of endothelial cells and pericytes and investigated its functionality. After inducing inflammation, the printed model exhibited significant junctional breakdown and upregulation of cytokines level. This model will be useful for an in-depth mechanistic study of cerebrovascular inflammation-associated pathology.