A Live Cell Imaging-Compatible Bioreactor for the Interrogation of Cellular Responses to Modulated Flow Conditions

Although being invaluable tools in biomedical research, traditional 2D cell culture models often fail in recapitulating complex environments, limiting their predictive power. To address this limitation, it have developed an open-source, low-cost system that combines long-term 3D cell culture under controlled perfusion conditions with live-cell imaging. By integrating bioprinted extracellular matrix-based scaffolds, this study mimics mechanical and biochemical cues experienced by cells within complex tissue contexts. Here, this system is used to generate a model of the cerebrospinal fluid-filled subarachnoid space to study responses of resident cell types such as meningothelial cells to altered fluid flow conditions. Using fluorescent biosensors, it demonstrates that meningothelial cells respond to modulated fluid flow by differentially activating focal adhesion kinase, a key mechanosensor. The model thus not only provides a powerful platform for investigating the impact of mechanical and other cues on cellular responses, but also bears great potential for the generation of impactful cell biological and pathophysiological models.