Abstract
A key problem hindering the regulation and approval of organ-on-chip technology by international drug regulatory agencies is the lack of standardization. This study aims to evaluate the impact of different concentrations of fetal bovine serum (FBS) on tight junction formation between cells in a microphysiological system (MPS). Hence, a standardized FBS concentration in cell culture media used for MPSs can be proposed. Caco-2, HepG2, and HK-2 immortal cell lines representing gut, liver and, kidney organ models, respectively were cultured in microphysiological devices and monitored in real-time for transepithelial electrical resistance (TEER) and pH over a six-days period. Glass-based microfluidic chips with embedded TEER electrodes were utilized to measure the impedance of the cell monolayers. Considering albumin, kidney injury molecule-1 (KIM-1), and alkaline phosphatase biomarkers, the results obtained using cell culture media containing 5% FBS were more physiologically relevant, when compared to media containing 0% and 10% FBS. E-cadherin confocal microscopy and a live dead cell assay were performed and compared with TEER data to confirm this claim. This optimized FBS concentration should enable microphysiological platforms to perform at an optimum cell culture capacity, facilitating robust pathophysiology, drug toxicity as well as, absorption, distribution, metabolism, and excretion (ADME) studies.
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