Abstract

Three-Dimensional Blood Vessels-on-Chips: Perfusion With Blood and Integration Into Organs-on-Chips

Andries van der Meer, Associate Professor, University of Twente, Scientific lead, Organ-on-Chip Center Twente

Small blood vessel dysfunction associated with chronic inflammation and oxidative stress is increasingly recognized as a key aspect of a wide array of diseases, such as heart failure with preserved ejection fraction, diabetic retinopathy and cerebral small vessel disease. Advanced in vitro models of small diameter blood vessels will become essential in understanding the pathophysiology of these diseases as well as in finding new strategies for prevention and treatment. Here, three-dimensional microfluidic models of small-diameter blood vessels or ‘blood vessels-on-chips’ are presented, which integrate (1) human vascular tissue, including human induced pluripotent stem cell-derived cells, (2) controlled flow patterns, and (3) human whole blood. Examples are given of how these blood vessels-on-chips can be used to study relevant parameters of vascular function and dysfunction, like cytokine release, platelet adhesion and permeability. Moreover, it is shown how blood vessels-on-chips can be integrated in more complex organs-on-chips like heart-on-chip and retina-on-chip models to study vascular dysfunction in more comprehensive disease models.