A vascularized glioblastoma multiforme within a 3D perfused microphysiological system: combining a self-organized microvasculature and a central venule in a hydrogel

International audienceThe blood-brain barrier (BBB) hampers the development of innovative drugs and nanovectors to treat neuro-pathologies, as brain cancers. The most frequent and aggressive brain tumor is the glioblastoma multiforme (GBM). After diagnostic, the median patient survival is about 12 months. Less than 5% of diagnosed patients are still alive after 3 years. The 3D-Glimpse project develops an organ-on-chip-like in-vitro physiological microsystem, as an alternative to animal testing. The microchip is perfused to mimic the blood flow, and instrumented with biosensors for an integrated detection of nanocarriers transport. The project is divided into 4 objectives, with preliminary results and prototypes for the first 3 objectives. <br&gt1) Development of the BBB-on-chip. The combination of two methodologies allows the 3D coculture of human brain cells (HBMEC: human brain microvascular endothelial cells, HP: human pericytes, HA: human astrocytes). They organize as a vascularized tissue in a hydrogel of extracellular matrix (collagen microfibers and fibrin). The barrier function is validated under a physiologically pertinent shear stress. <br&gt2) Comparison of the BBB-on-chip in a healthy versus pathological context. The microchip is adapted to fit the microenvironment of a vascularized brain tumor, with adjunction of GBM cells (U87) to create a GBM-on-chip. <br&gt3) Instrumentation of the BBB-on-chip. Biosensing integration relies on functionalized piezo-electrical substrates (lithium niobate) for detecting the transport of nanocarriers through the BBB and a micro-processed porous membrane.