Development of a Vessel-on-a-Chip as a Viral Infection Model and Antiviral Drug Screening Platform with Viral Mimics

COVID-19 pandemic and recurrent influenza outbreaks have underscored the urgent need for robust in vitro systems to model viral infections and facilitate Antiviral drug screening. Using organ-on-a-chip technologies, endothelial cells were cultured to recapitulate a three-dimensional (3D) microvascular environment enhanced with higher physiologic relevance. This work aims to construct a simple yet biologically representative disease model that can be easily applied to drug screening in a high-throughput, time-efficient manner. To mimic viral infections, inflammation was induced using virus-mimicking particles, specifically polyinosinic-polycytidylic acid, while anti-inflammatory drugs RVX-208, JQ-1, and PFI-1 were evaluated for their therapeutic potential in reducing inflammation. Imaging analysis revealed that a polyinosinic-polycytidylic acid concentration of 5 μg/mL yielded the highest VCAM-1 expression, an indication of inflammation. Combining the results from VCAM-1 intensity measurements and vascular diameter changes in drug-treated cases, the effective dose of each drug was suggested. This vessel-on-a-chip platform demonstrates significant potential for advancing studies on vascular pathophysiology and Antiviral treatments, offering convenient approaches for investigating both viral agents and therapeutic drugs.

BRD4 inhibitors; VCAM-1; poly(I:C)-induced Inflammation; vasculogenesis; vessel-on-a-chip; viral mimicry.