| dc.description.abstract | While animal models are frequently used to explore the macroscale effects of various substances and processes within the blood-brain barrier (BBB), they often fail to fully recapitulate human response or prohibit mechanistic examination. Although in vitro BBB models have the potential to address these challenges, these simplified models have yet to achieve all the characteristics of their in vivo human counterparts. This work explores ways to improve the established transwell cell culture platform to make it a more physiologically relevant model. Human primary, rat primary, and human immortalized cells lines were compared in terms of morphology, transendothelial electrical resistance (TEER), and permeability. Often overlooked culturing parameters are also examined to understand their impact on barrier formation. Special attention was paid to how different preparations and loading styles could potentially alter results. Finally, results are evaluated within the context of current literature standards.
To improve current BBB quantification strategies, an open-source, low-cost, 3D printed platform was also developed to reliably measure TEER levels in cell monolayers and co-cultures. The device was manufactured by embedding silver wires into a 3D printed housing that can easily be connected to commercial voltohmmeters. This prototype was characterized in comparison to two commercial chopstick electrode standards. In addition, this device was also studied for manufacturing variation and measurement stability over time. The final version produced comparable results to commercial standards with lower overall background while providing researchers with a low-cost customizable device that can be optimized to fulfill their own research needs. | |
