The endothelium at the crossroads of multi-organ pathology: Insights from organ-on-chip models.

Abstract

Endothelial barrier function is indispensable in maintaining vascular-tissue-organ homeostasis. Altered release of vasoactive substances along with fluctuating shear stress patterns result in an impaired barrier function leading to transmigration of blood components, tumor infiltrates and pathogens. Organ-on-chip (OoC) technology leverage microfabrication techniques to develop dynamic, three-dimensional (3D) in vitro platforms that closely mimic the structural and functional characteristics of human tissues, including the vasculature. These systems offer powerful tools for modeling disease mechanisms with high physiological relevance and are increasingly utilized in drug development, diagnostics, and therapeutic screening. By integrating biomimetic vascular environments, OoC platforms allow for the investigation of how endothelial barrier disruption, inflammatory signaling, and mechanical cues contribute to pathophysiology. Importantly, since endothelial dysfunction often precedes clinical symptoms, these models offer promising avenues for early disease detection and intervention. Together, these approaches provide a roadmap for using organ-on-chip systems to dissect vascular contributions to disease and to improve predictive, human-relevant preclinical models.