Human Blood‐Brain Tumor Barrier on a Chip to Investigate Personalized Treatment for Glioblastoma Patients

ABSTRACT The inherent characteristics of glioblastoma (GBM), including tumoral heterogeneity and invasive capacity, combined with the presence of the blood‐brain tumor barrier (BBTB), present challenges in developing effective treatment for GBM. Especially, the margins of GBM, where GBM cells infiltrate normal brain tissue, exhibit high resistance to therapies. Despite the difficulties in controlling tumor progression within this region, the GBM margin remains a critical area to be studied. Here we report a microengineered model that mimics the BBTB within the GBM margin, incorporating a 3D network of normal astrocytes and GBM cells isolated from patients newly diagnosed with GBM. The interaction between GBM cells and stromal cells results in increased vascular permeability, reactive gliosis, alterations in astrocyte behavior and immune responses to foster tumor invasiveness and progression. We compare patient‐specific tumor responses to conventional chemotherapy and immune polarization in our BBTB on a chip model with clinical outcomes, demonstrating the capability of the model to predict personalized drug responses. Our BBTB model may serve as a personalized tool to examine the interactions between tumors and normal brain tissue, ultimately facilitating the screening of personalized medicine for GBM treatment.