A 3D-printed blood-brain barrier model with tunable topology and cell-matrix interactions.

Authors

Louis S PaoneFollow
Mohammed Mehdi Benmassaoud
Aidan Curran
Sebastián L Vega
Peter A Galie

Document Type

Article

Version Deposited

Published Version

Open Access Funding Source

Open Access Publishing Fund

Publication Date

10-20-2023

Publication Title

Biofabrication

DOI

10.1088/1758-5090/ad0260

Abstract

Recent developments in digital light processing (DLP) can advance the structural and biochemical complexity of perfusable in vitro models 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.

Comments

Publication of this article was supported by the Rowan University Libraries 2023-24 Open Access Publishing Fund.

Recommended Citation

Paone, Louis S; Benmassaoud, Mohammed Mehdi; Curran, Aidan; Vega, Sebastián L; and Galie, Peter A, "A 3D-printed blood-brain barrier model with tunable topology and cell-matrix interactions." (2023). Henry M. Rowan College of Engineering Departmental Research. 323.
https://rdw.rowan.edu/engineering_facpub/323

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.