Cerebrovascular-Specific Extracellular Matrix Bioink Promotes Blood-Brain Barrier Properties.

Abstract

Chronic neuroinflammation is a principal cause of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The blood-brain barrier predominantly comprises endothelial cells, and their intercellular communication with pericytes and other cell types regulates neuroinflammation. Here, we develop a tubular, perfusable model of human cerebrovascular tissues to study neurodegenerative diseases using cerebrovascular-specific extracellular matrix bioink, derived from a complementary blend of brain- and blood-vessel-derived extracellular matrices. The endothelial cells and pericytes in the bioprinted constructs spontaneously self-assemble into a dual-layered structure, closely mimicking the anatomy of the blood-brain barrier. Moreover, the mature cerebrovascular tissue shows physiological barrier functions and neuroinflammatory responses, indicating its potential for developing models of neuroinflammation-related pathologies. Collectively, our study demonstrates that furnishing a cerebrovascular-specific microenvironment can guide the cells to have native-like anatomical relevance and functional recapitulation in vitro.