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Bio-Design and Manufacturing  2024 Vol.7 No.5 P.624-636

http://doi.org/10.1007/s42242-024-00289-z


Ionic liquid-based transparent membrane-coupled human lung epithelium-on-a-chip demonstrating PM0.5 pollution effect under breathing mechanostress


Author(s):  Bilgesu Kaya, Ozlem Yesil-Celiktas

Affiliation(s):  Department of Bioengineering, Faculty of Engineering, Ege University, Izmir 35100, Türkiye; more

Corresponding email(s):   ozlem.yesil.celiktas@ege.edu.tr

Key Words:  Ionic liquid-based membrane · Lung · Epithelial barrier · Mechanostress · Organ-on-chip · Silica particles


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Bilgesu Kaya, Ozlem Yesil-Celiktas. Ionic liquid-based transparent membrane-coupled human lung epithelium-on-a-chip demonstrating PM0.5 pollution effect under breathing mechanostress[J]. Journal of Zhejiang University Science D, 2024, 7(5): 624-636.

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Abstract: 
The plausibility of human exposure to particulate matter (PM) has witnessed an increase within the last several years. PM of different sizes has been discovered in the atmosphere given the role of dust transport in weather and climate composition. As a regulator, the lung epithelium orchestrates the innate response to local damage. Herein, we developed a lung epithelium-ona-chip platform consisting of easily moldable polydimethylsiloxane layers along with a thin, flexible, and transparent ionic liquid-based poly(hydroxyethyl) methacrylate gel membrane. The epithelium was formed through the culture of human lung epithelial cells (Calu-3) on this membrane. The mechanical stress at the air–liquid interface during inhalation/exhalation was recapitulated using an Arduino-based servo motor system, which applied a uniaxial tensile strength from the two sides of the chip with 10% strain and a frequency of 0.2 Hz. Subsequently, the administration of silica nanoparticles (PM0.5) with an average size of 463 nm to the on-chip platform under static, dynamic, and dynamic + mechanical stress (DMS) conditions demonstrated the effect of environmental pollutants on lung epithelium. The viability and release of lactate dehydrogenase were determined along with proinflammatory response through the quantification of tumor necrosis factor-α, which indicated alterations in the epithelium.

土耳其Yesil-Celiktas等 | 基于离子液体的透明膜耦合人体肺上皮芯片在呼吸机械应力下揭示PM0.5污染效应

本研究论文聚焦基于离子液体的透明膜耦合人体肺上皮芯片在呼吸机械应力下揭示PM0.5污染效应。近年来,人类暴露于不同尺寸颗粒物(PM)的可能性不断增加。由于粉尘传输对气候和天气的影响,已在大气中检测到不同大小的颗粒物。肺上皮细胞作为调节器,负责协调对局部损伤的先天性免疫反应。本研究开发了一种肺上皮芯片平台,由易于模塑的聚二甲基硅氧烷(PDMS)层与一层薄而灵活的透明离子液体基聚(羟乙基)甲基丙烯酸酯凝胶膜组成。通过在该膜上培养人肺上皮细胞(Calu-3),形成了肺上皮细胞层。采用基于Arduino的伺服电机系统在吸气/呼气期间于气-液界面施加单轴拉伸力(10%应变,0.2 Hz频率),从而模拟机械应力。随后,在静态、动态和动态+机械应力(DMS)条件下向该芯片平台加入平均粒径为463 nm的二氧化硅纳米颗粒(PM0.5),以研究环境污染物对肺上皮的影响。通过测定乳酸脱氢酶释放及肿瘤坏死因子-α(TNF-α)的量化分析促炎反应,结果显示出上皮细胞的变化。

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