Cho Minkyung, Park Je-Kyun
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
KAIST Institute for Health Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
ACS Biomater Sci Eng. 2020 Sep 14;6(9):5326-5336. doi: 10.1021/acsbiomaterials.0c00748. Epub 2020 Aug 31.
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.
构建一个模拟动脉的三维体外模型,通过提出一种能够以可控方式重现天然血管状态的先进模型,在理解血管疾病的病理细胞行为和机制方面发挥着重要作用。由于模型的几何形状和细胞结构对于重现动脉血流动力学和细胞功能至关重要,因此在构建模型时,有必要模拟几何形状并诱导细胞形成适当的形态和取向。在本研究中,将动脉壁中的主要成分平滑肌细胞(SMC)和内皮细胞(EC)在与聚二甲基硅氧烷(PDMS)流体腔室模块相连的多通道装置中共培养,以并行构建一个可灌注的三维体外模拟人体动脉多通道系统。在共培养模型中,具有皱纹表面的圆形PDMS通道引导SMC的方向性和收缩形态,并且培养基灌注如在体内一样诱导汇合的EC层的方向性。展示了细胞的蛋白质标志物和合成的细胞外基质。由于多通道连接到装置中的微流体模块,因此可以轻松控制微环境条件,并在单个流动系统中并行构建共培养模型。通过3D打印模具构建了可以在诸如动脉疾病的直径、壁面剪应力和几何形状等设计中进行调整的共培养模型,以重现各种细胞微环境并有效地模拟血管。最后,使用具有四种不同狭窄程度通道的装置比较了壁面剪应力对细胞的影响,并进行了并行研究。