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This study provides a method to assess the impact of circulating plasma factors on microvascular integrity by using a recently developed microvessel‐on‐a‐chip platform featuring the human endothelium that is partly surrounded by the extracellular matrix. The system is high‐throughput, which allows parallel analysis of organ‐level microvessel pathophysiology, including vascular leakage. Ethylenediaminetetraacetic acid plasma samples are mixed with inhibitors for recalcification of the plasma samples to avoid activation of the coagulation‐ or complement system. Moreover, the assay is validated by spiking vascular endothelial growth factor, histamine, or tumor necrosis factor alpha to recalcified plasma and confirms their modulation of microvessel barrier function at physiologically relevant concentrations. Finally, this study shows that perfusing the microvessels with recalcified plasma samples of coronavirus disease‐2019 patients, with a confirmed proinflammatory profile, results in markedly increased leakage of the microvessels. The assay provides opportunities for diagnostic screening of inflammatory or endothelial disrupting plasma factors associated with endothelial dysfunction.
Microvessels‐on‐chips are advanced in vitro models that are currently considered as future replacements of animal models. However, the high‐throughput use of microvessels‐on‐chips for patient‐on‐a‐chip studies is still lacking. This study develops an innovative method for screening plasma samples in the microvessel‐on‐a‐chip platforms that can be potentially suitable for the early detection and prediction of microvascular disease in individual patients.