Development and application of a blood-brain barrier-on-chip model for investigating microglial phenotypic modulation in glioblastoma

Glioblastoma (GBM) is a highly aggressive brain tumour characterized by a complex tumour microenvironment (TME) that interacts intricately with immune cells. This study aimed to develop a GBM-on-chip model to investigate the interactions between the tumour and its microenvironment in a controlled system, particularly with microglial cells, which are the resident immune cells of the brain. A microfluidic device was fabricated in polydimethylsiloxane (PDMS) using microfabrication, to mimic the structural and functional characteristics of the GBM TME. The chip comprised separate compartments for cerebral vasculature and brain parenchyma, facilitating the observation of cellular behaviours and interactions. To assess the microglial response to the tumour environment, we focused on the phenotypic transition of microglia from the pro-inflammatory M1 state to the anti-inflammatory M2 state. Interferon-gamma (IFN-γ) was used as a positive control to induce microglial activation and validate the model's functionality. The study revealed significant changes in microglial morphology and behaviour in response to GBM cells, highlighting the dynamic nature of the immune response within the TME. The findings underscore the relevance of the GBM-on-chip model for studying GBM and provide insights into the interactions between tumours and immune cells. This research contributes to the development of more effective therapeutic strategies for GBM by facilitating a better understanding of the cellular mechanisms involved in tumour progression and immune modulation.