Construction of microfluidic blood-brain barrier model assisted by 3D coculture on cellulose fiber

Abstract

In this study, we fabricated a microfluidic device to mimic the human blood-brain barrier (BBB) in vitro, comprising a cellulose fiber membrane sandwiched between two silicone elastomer poly(dimethylsiloxane) (PDMS) layers. The PDMS layers were bonded using the oxygen plasma surface activation method. The encased cellulose fiber separated the intersection of channels in the PDMS layers and functioned as a three-dimensional scaffold for cell attachment and stretching. Human astrocytes and human brain vein pericytes were seeded into the cellulose fiber by a mixture of collagen and cells. Human umbilical vein endothelial cells were subsequently seeded into the cellulose fiber to form an in vitro BBB model. Cell viability, F-actin formation, and transendothelial electrical resistance (TEER) were used to evaluate BBB formation. Albumin-fluorescein isothiocyanate conjugate protein bovine (FITC-albumin) and nanovesicles were used to evaluate the ability of the model to work as an in vitro model of BBB. Over 7 days, the model achieved cell viability over 90% and a TEER over 300 omega x cm(2). The model also expressed selective permeability when injected with FITC-albumin and nanovesicles. Altogether, the model provided an easy to replicate and inexpensive platform for in vitro drug screening. This design could be further modified to create models for other blood-tissue barriers, such as the blood-air barrier.