A 3D-printed blood-brain barrier model with tunable topology and cell-matrix interactions. Biofabrication 2023 Oct 20;16(1)
Date
10/12/2023Pubmed ID
37820611DOI
10.1088/1758-5090/ad0260Scopus ID
2-s2.0-85174641791 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Recent developments in digital light processing (DLP) can advance the structural and biochemical complexity of perfusablein vitromodels of the blood-brain barrier. Here, we describe a strategy to functionalize complex, DLP-printed vascular models with multiple peptide motifs in a single hydrogel. Different peptides can be clicked into the walls of distinct topologies, or the peptide motifs lining channel walls can differ from those in the bulk of the hydrogel. The flexibility of this approach is used to both characterize the effects of various bioactive domains on endothelial coverage and tight junction formation, in addition to facilitating astrocyte attachment in the hydrogel surrounding the endothelialized vessel to mimic endothelial-astrocyte interaction. Peptides derived from proteins mediating cell-extracellular matrix (e.g. RGD and IKVAV) and cell-cell (e.g. HAVDI) adhesions are used to mediate endothelial cell attachment and coverage. HAVDI and IKVAV-lined channels exhibit significantly greater endothelialization and increased zonula-occluden-1 (ZO-1) localization to cell-cell junctions of endothelial cells, indicative of tight junction formation. RGD is then used in the bulk hydrogel to create an endothelial-astrocyte co-culture model of the blood-brain barrier that overcomes the limitations of previous platforms incapable of complex topology or tunable bioactive domains. This approach yields an adjustable, biofabricated platform to interrogate the effects of cell-matrix interaction on blood-brain barrier mechanobiology.
Author List
Paone LS, Benmassaoud MM, Curran A, Vega SL, Galie PAAuthor
Mehdi Benmassaoud PhD, BS, MSc Postdoctoral Researcher in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Blood-Brain BarrierEndothelial Cells
Hydrogels
Oligopeptides
Peptides
Printing, Three-Dimensional
