Development of a perfusable 3D in vitro human 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 artery 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 thesis, I present a perfusable three-dimensional (3D) in vitro human artery-mimicking multichannel system for artery disease models. Smooth muscle cells (SMCs) and endothelial cells (ECs), which were the main elements in the arterial wall, were co-cultured in a multichannel device connected with fluidic chamber modules to parallelly fabricate a pefusable 3D in vitro human artery-mimicking multichannel system. A circular polydimethylsiloxane 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. Various geometries of models were obtained by 3D-printed molds to recapitulate various cellular microenvironments and to model vessels effectively. After the establishment of the models, a modular system was introduced to demonstrate stenosis and inflammation and to study physical and chemical effects on the biomimetic artery models. The manipulation became reproducible and stable through modularization, and each module could be replaced according to analytical purposes. A microfluidic concentration gradient generator module was used to achieve the cellular state of inflamed lesions by providing tumor necrosis factor (TNF)-α, in addition to the stenosis structure and disturbed flow by tuning the channel geometry. The influence of shear stress, stenosis geometry, TNF-α concentration, and cell–cell interaction through co-culture, on vascular stenosis and inflammation, was investigated in a high-throughput manner.