TUNABLE 3D-PRINTED BIOMATERIALS FOR PERFUSED IN VITRO MODELS OF THE BLOOD-BRAIN BARRIER

In vitro models have tremendous utility for improving our understanding of complex physiological and pathophysiological processes in a more controlled environment than animal models, in addition to incorporating human cells to overcome species-specific disparities. This dissertation describes innovations in biomaterial-based fabrication processes that advance in vitro models of the blood-brain barrier, providing the opportunity to evaluate the effects of cell-matrix interactions on barrier integrity, additives to reduce viscous drag of blood flow, and molecular mechanisms underlying the cellular response to amyloid beta in the context of Alzheimer’s disease. The core technology underlying this advance is a biomaterial compatible with digital light processing that yields spatial control of tunable, bioactive peptide motifs. The biomaterial can be 3D-printed into hydrogels with complex and interpenetrating topologies with peptides linked both to the lining and within the bulk of the material. Section 1 of the results details experiments interrogating the effect of peptide motifs on blood-brain barrier integrity. Section 2 focuses on using the 3D model as a testbed to evaluate drag-reducing polymers and the interaction between the endothelium and whole blood. Section 3 involves the incorporation of amyloid beta peptides and their effect on gene expression of induced pluripotent stem cell-derived endothelium. Additionally, this dissertation also describes commercialization of this technology for the perfusion of vascularized organoids.