Biomanufacturing of a novel in vitro biomimetic blood-brain barrier model

A glioma is a malignant tumor that severely threatens human health. However, it is difficult for most therapeutic agents to penetrate through the blood-brain barrier (BBB) and exhibit their antineoplastic activity in the brain. In this article, a biomimetic in vitro BBB model was created by a composite process, this model can provide a significant foundation for the research of drug transport, tumor treatment, tumor microenvironment and other fields. A series of tests and comparative experiments were performed to evaluate this model. The tests showed that the model enabled preliminary simulation of the structure and function of the BBB. Experimental results demonstrated: (1) the new technology enabled controlled release of growth factors and successfully induced endothelial progenitor cells into endothelial cells. Compared with the traditional gold standard, the Transwell model, the expression of four specific proteins that are related to the BBB characteristics was significantly increased (alkaline phosphatase(ALP) by 89.82%, gamma-GT by 88.86%, zonula occludens-1 (ZO-1) by 57.40%, and Claudin-5 by 102.32%) in this model; (2) astrocytes had a promoting effect on the microvascular endothelial cells to form tight junction (ZO-1 increased by 249.35%, Claudin-5 increased by 184.99%), and there was a great difference between whether these two types of cells were contact cultured or not; (3) the gelatinous cell U118 had a destructive effect on the tight junction of BBB (ZO-1 decreased by 55.86%, Claudin-5 decreased by 37.84%).