02646nas a2200301   4500000000100000000000100001008004100002653001100043653002000054653001700074653001700091653001700108653001900125653003200144653002000176100001100196700002000207700001600227700001300243700002300256700002100279245013100300856006300431300001100494490000800505520181700513022001402330                                       d10aartery10aatherosclerosis10abiomechanics10aimmune cells10aInflammation10amechanobiology10amicro physiological systems10aorgan-on-a-chip1 aYu Hou1 aGeorgios Ziakas1 aTim Hopkins1 aWen Wang1 aHazel R. C. Screen1 aMartin M. Knight00aHuman coronary artery organ-chip with circulating immune cells recapitulates anti-inflammatory effect of pulsatile wall strain  uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/inmd.70114  ae701140 vn/a3 aInflammation is a precursor to vascular diseases, including atherosclerosis, and is modulated by the local biomechanical environment. There is a need for in vitro models to advance understanding and test new therapeutics. This study describes the development and characterisation of a human coronary artery organ-chip model of vascular inflammation with physiological biomechanical stimulation. Human coronary artery endothelial cells and smooth muscle cells were cultured on appropriate extracellular matrices in the two adjoining channels of the Chip-S1® (Emulate Inc). Both endothelial and smooth muscle cells demonstrated characteristic phenotypic identity, as shown by expression of CD31 and α-SMA, respectively. Application of pulsatile tensile strain induced alignment of both cell types, perpendicular to strain direction, as seen in vivo. Addition of TNF-α to the vascular channel drove an inflammatory response in both cell types, as shown by upregulation of ICAM-1 and P65, and attachment and invasion of circulating THP-1 monocytes. Analysis revealed spatial variation in strain with 12% in the centre of the chip, and 5% towards the ends. Pulsatile tensile strain reduced the inflammatory response to TNF-α, with a greater inflammatory response in areas of lower strain, further replicating in vivo behaviour. In conclusion, we present a fully characterised, tri-culture model of the human coronary artery with endothelial and smooth muscle cells and circulating immune cells. This model successfully recapitulates the physiological effects of pulsatile vessel dilation on cell morphology and localised inflammatory susceptibility. Our model was developed upon a commercially available, organ-chip platform, allowing for rapid adoption for therapeutic testing, and fundamental discovery science.  a2832-6245