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

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.