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, Korea.
KAIST Institute for Health Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea.
Micromachines (Basel). 2021 Dec 8;12(12):1528. doi: 10.3390/mi12121528.
Inflammation and the immune response in atherosclerosis are complex processes involving local hemodynamics, the interaction of dysfunctional cells, and various pathological environments. Here, a modular multichannel system that mimics the human artery to demonstrate stenosis and inflammation and to study physical and chemical effects on biomimetic artery models is presented. Smooth muscle cells and endothelial cells were cocultured in the wrinkled surface in vivo-like circular channels to recapitulate the artery. An artery-mimicking multichannel module comprised four channels for the fabrication of coculture models and assigned various conditions for analysis to each model simultaneously. The manipulation became reproducible and stable through modularization, and each module could be replaced according to analytical purposes. A chamber module for culture was replaced with a microfluidic concentration gradient generator (CGG) module to achieve the cellular state of inflamed lesions by providing tumor necrosis factor (TNF)-α, in addition to the stenosis structure by tuning the channel geometry. Different TNF-α doses were administered in each channel by the CGG module to create functional inflammation models under various conditions. Through the tunable channel geometry and the microfluidic interfacing, this system has the potential to be used for further comprehensive research on vascular diseases such as atherosclerosis and thrombosis.
动脉粥样硬化中的炎症和免疫反应是复杂的过程,涉及局部血流动力学、功能失调细胞的相互作用以及各种病理环境。在此,我们展示了一种模块化多通道系统,该系统模拟人体动脉以演示狭窄和炎症,并研究对仿生动脉模型的物理和化学影响。平滑肌细胞和内皮细胞在体内样的有褶皱表面的圆形通道中共培养以重现动脉。一个模拟动脉的多通道模块包括四个用于构建共培养模型的通道,并同时为每个模型分配各种分析条件。通过模块化,操作变得可重复且稳定,并且每个模块可根据分析目的进行更换。用于培养的腔室模块被微流控浓度梯度发生器(CGG)模块取代,通过调节通道几何形状来提供肿瘤坏死因子(TNF)-α,除了形成狭窄结构外,还可实现炎症病变的细胞状态。CGG模块在每个通道中给予不同剂量的TNF-α,以在各种条件下创建功能性炎症模型。通过可调节通道几何形状和微流控接口,该系统有潜力用于对动脉粥样硬化和血栓形成等血管疾病进行进一步的综合研究。