Knowledge Bank

The blood brain barrier (BBB) is essential to neural function as it prevents foreign molecules from entering the brain. While various in vitro and in vivo models attempt to replicate the BBB, most fall short in terms of isolated cell types and lack of microglia, a vital glial cell which alerts the system of toxins. Additionally, glioblastoma (GBM) is a lethal brain disease with no viable treatment options. By successfully modeling the BBB and studying its immune response, one could gain a better understanding of how to utilize neuroinflammation to penetrate the BBB to deliver treatment to a GBM tumor. This study does so by developing an in vitro BBB organ-on-a-chip model comprised of human brain cells and a brain-mimetic hydrogel. This is done using a polydimethylsiloxane microfluidic device with astrocytes and microglia populating a bioengineered hydrogel containing a pericyte and endothelial cell-lined vascular lumen structure, which is then analyzed via immunostaining and permeability assessments. The model proved to replicate human BBB functions after numerous assessments, such as by showing low permeability to small molecules as well as appropriate cell-specific marker expression. The addition of GBM cells to the system showed that the function of the BBB responds to the tumor cell population. Further, integrating microglia into the BBB model also influenced its function and the cellular phenotypes within. As a whole, these results indicate the usefulness of this model as a tool to investigate disease progression of GBM and functionality of the BBB.