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Construction of microfluidic blood–brain barrier model assisted by 3D coculture on cellulose fiber
Microsystem Technologies ( IF 1.6 ) Pub Date : 2021-01-05 , DOI: 10.1007/s00542-020-05197-7
Duong Duy Duong , Jisung Kwak , Hyun Seok Song , Nae Yoon Lee

In this study, we fabricated a microfluidic device to mimic the human blood–brain barrier (BBB) in vitro, comprising a cellulose fiber membrane sandwiched between two silicone elastomer poly(dimethylsiloxane) (PDMS) layers. The PDMS layers were bonded using the oxygen plasma surface activation method. The encased cellulose fiber separated the intersection of channels in the PDMS layers and functioned as a three-dimensional scaffold for cell attachment and stretching. Human astrocytes and human brain vein pericytes were seeded into the cellulose fiber by a mixture of collagen and cells. Human umbilical vein endothelial cells were subsequently seeded into the cellulose fiber to form an in vitro BBB model. Cell viability, F-actin formation, and transendothelial electrical resistance (TEER) were used to evaluate BBB formation. Albumin-fluorescein isothiocyanate conjugate protein bovine (FITC-albumin) and nanovesicles were used to evaluate the ability of the model to work as an in vitro model of BBB. Over 7 days, the model achieved cell viability over 90% and a TEER over 300 Ω × cm2. The model also expressed selective permeability when injected with FITC-albumin and nanovesicles. Altogether, the model provided an easy to replicate and inexpensive platform for in vitro drug screening. This design could be further modified to create models for other blood–tissue barriers, such as the blood–air barrier.



中文翻译:

纤维素纤维3D共培养辅助微流血脑屏障模型的建立

在这项研究中,我们制造了一种微流体装置,以在体外模拟人血脑屏障(BBB),该装置包括夹在两个有机硅弹性体聚二甲基硅氧烷(PDMS)层之间的纤维素纤维膜。使用氧等离子体表面活化方法结合PDMS层。包裹的纤维素纤维分隔了PDMS层中通道的交叉点,并充当用于细胞附着和拉伸的三维支架。通过胶原蛋白和细胞的混合物将人星形胶质细胞和人脑静脉周细胞接种到纤维素纤维中。随后将人脐静脉内皮细胞接种到纤维素纤维中以形成体外BBB模型。细胞活力,F-肌动蛋白形成和跨内皮电阻(TEER)用于评估BBB形成。白蛋白-异硫氰酸荧光素共轭蛋白牛(FITC-白蛋白)和纳米囊泡用于评估该模型作为BBB体外模型的能力。在7天的时间里,该模型的细胞存活率超过90%,TEER超过300Ω×cm2。当注射FITC-白蛋白和纳米囊泡时,该模型还表达了选择性渗透性。总之,该模型为体外药物筛选提供了易于复制且廉价的平台。可以进一步修改此设计,以创建其他血液组织屏障(例如血液-空气屏障)的模型。

更新日期:2021-01-05
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