Engineering advanced in vitro models of endothelial dysfunction.

Endothelial dysfunction is an important initiator of cardiovascular disease, the leading cause of death globally, and often manifests in arterial regions with disturbed blood flow. Experimental model advances have crucially helped unravel physiological mechanisms. While in vivo models provide a dynamic environment, they often fail to mimic human physiology precisely and face significant ethical barriers. Advanced in vitro models, including organs-on-chips and bioreactors, combine human cells and blood flow to accurately replicate endothelial dysfunction. Newer models have enhanced scalability and accuracy, with organs-on-chips commonly outperforming standard preclinical methods. Importantly, recent endothelial dysfunction discoveries leverage dynamic models to identify and evaluate clinically promising therapeutics. Here, we examine these developments and explore opportunities to develop next-generation in vitro models of endothelial dysfunction.