Fabrication of a Perfusable 3D In Vitro Artery-Mimicking Multichannel System for Artery Disease Models

Abstract

Fabrication of a 3D in vitro model that mimics the artery takes an important role in understanding pathological cell behaviors and mechanisms of vascular diseases by proposing an advanced model that can recapitulate a native vessel condition in a controlled manner. Because a model geometry and the structure of cells are significant for the recapitulation of the hemodynamics of arterial and cell functions, it is necessary to mimic geometries and to induce the proper morphology and orientation of the cells when fabricating a model. In this study, smooth muscle cells (SMCs) and endothelial cells (ECs), which were the main elements in the arterial wall, were cocultured in a multichannel device connected with polydimethylsiloxane (PDMS) fluidic chamber modules to parallelly fabricate a pefusable 3D in vitro human artery-mimicking multichannel system. In the coculture model, a circular PDMS channel with a wrinkled-surface guided directionality and contractile morphology to SMCs, and media perfusion induced directionality to a confluent EC layer as in vivo. Protein markers of cells and synthesized extracellular matrices were demonstrated. Because multichannels were connected to a microfluidic module in a device, it was possible to easily control the microenvironmental conditions and to fabricate coculture models in parallel with a single flow system. Coculture models that can be tuned in designs such as diameter, wall shear stress, and geometry of artery disease were constructed by 3D-printed molds to recapitulate various cellular microenvironments and to model vessels effectively. Finally, the effect of wall shear stress on cells was compared using a device with four different degrees of stenosis channels and investigated in parallel.