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Hybrid elastomer-plastic microfluidic device as a convenient model for mimicking the blood-brain barrier in vitro.
Biomedical Microdevices ( IF 3.0 ) Pub Date : 2019-11-04 , DOI: 10.1007/s10544-019-0446-1
Phuoc Quang Huy Nguyen 1 , Duong Duy Duong 1 , Jun Dae Kwun 2 , Nae Yoon Lee 1
Affiliation  

In this study, we fabricated a hybrid elastomer–plastic microdevice using the silicone elastomer poly(dimethylsiloxane) (PDMS) and the plastic polycarbonate (PC), to mimic the human blood–brain barrier (BBB) in vitro. Specifically, the microchannel-imprinted elastomer was first coated with 3-aminopropyltriethoxysilane to produce amine-terminated PDMS. Then, simply by conformal contact at room temperature, the amine-functionalized PDMS was bonded to pristine PC through the formation of urethane linkages. Aside from realizing device bonding, the amine functionalization also assisted in subsequent dopamine coating to form polydopamine and provide a stable surface for culturing human endothelial cells and central nervous system-related cells (e.g., astrocytes) inside the microchannels. Successful mimicking of the BBB-like microenvironment was assessed by 3D co-culturing of human endothelial cells and astrocytes, where the microdevice was verified as an acceptable in vitro BBB model according to the following four criteria: the formation of tight junctions at the cell–cell boundaries of the endothelial cells, evaluated by the expression of the tight junction marker ZO-1; the formation of actin filaments, evaluated using rhodamine phalloidin dye; low permeability, tested using the fluorescent tracer 40-kDa FITC-dextran; and good transendothelial electrical resistance (a measure of the tight junction integrity formed between the endothelial cells). The fabricated PDMS–PC microfluidic device ensured simple yet stable device sealing, and simultaneously enhanced BBB-mimicking cell attachment, thus fulfilling all major criteria for its application as a convenient in vitro BBB model.

中文翻译:

混合弹性体-塑料微流体装置,作为体外模拟血脑屏障的便捷模型。

在这项研究中,我们使用有机硅弹性体聚二甲基硅氧烷(PDMS)和塑料聚碳酸酯(PC)制造了混合弹性体-塑料微器件,以在体外模拟人血脑屏障(BBB)。具体地,首先用3-氨基丙基三乙氧基硅烷涂覆微通道印迹的弹性体,以产生胺封端的PDMS。然后,仅通过在室温下进行保形接触,即可通过形成氨基甲酸酯键将胺官能化的PDMS与原始PC结合。除了实现装置键合之外,胺官能化还协助随后的多巴胺涂层形成聚多巴胺,并为在微通道内培养人内皮细胞和中枢神经系统相关细胞(例如星形胶质细胞)提供稳定的表面。通过人类内皮细胞和星形胶质细胞的3D共培养评估了BBB样微环境的成功模仿,其中微装置被证实是可接受的体外根据以下四个标准建立BBB模型:通过紧密连接标记ZO-1的表达评估内皮细胞在细胞间边界上紧密连接的形成;用若丹明鬼笔环肽染料评估肌动蛋白丝的形成;低渗透性,使用荧光示踪剂40 kDa FITC-葡聚糖测试;以及良好的跨内皮电阻(衡量内皮细胞之间紧密连接完整性的量度)。所制造的PDMS-PC微流体装置确保了简单而稳定的装置密封,同时增强了BBB模拟细胞的附着力,从而满足了将其用作便利的体外BBB模型的所有主要标准。
更新日期:2019-11-04
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