Lung-on-a-chip devices could provide new strategies for a biomimetic lung cell microenvironment and construction of lung disease models in vitro, and are expected to greatly promote the development of drug evaluation, toxicological detection, and disease model building. In this study, we developed a novel poly (lactic-co-glycolic acid) (PLGA) nanofiber/polydimethylsiloxane (PDMS) microporous composite membrane-sandwiched lung-on-a-chip to perform anti-tumor drug testing. The composite membrane was characterized, and the results showed that it was permeable to molecules and thus could be used to study small-molecule drug diffusion. In addition, the microchip could apply perfusion fluids to simulate blood flow under extremely low fluid shear stress, and could also simulate the spherical-like shape of the alveoli by deformation of the composite membrane. Using this chip, we evaluated the anti-tumor drug efficacy of gefitinib in two kinds of non-small cell lung cancer cells, the lung adenocarcinoma NCI-H1650 cell line and the large cell lung cancer NCI-H460 cell line. We further probed the resistance of NCI-H460 cells to gefitinib under normoxic and hypoxic conditions. The established composite membrane-sandwiched lung chip can simulate more biochemical and biophysical factors in the lung physiological and pathological microenvironment, and it has important applications in the personalized treatment of lung tumors. It is expected to play a potential role in clinical diagnosis and drug screening.

中文翻译：

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PLGA纳米纤维/ PDMS微孔复合膜夹心微芯片，用于药物测试

片上肺装置可以为仿生肺细胞微环境和体外建立肺部疾病模型提供新的策略，并有望极大地促进药物评估，毒理学检测和疾病模型构建的发展。在这项研究中，我们开发了一种新型的聚乳酸-乙醇酸（PLGA）纳米纤维/聚二甲基硅氧烷（PDMS）微孔复合膜夹心肺片，以进行抗肿瘤药物测试。对复合膜进行了表征，结果表明该复合膜具有分子渗透性，可用于研究小分子药物的扩散。此外，微芯片可以在极低的流体剪切应力下施加灌注流体来模拟血流，并且还可以通过复合膜的变形来模拟肺泡的球形形状。使用该芯片，我们评估了吉非替尼在两种非小细胞肺癌细胞，即肺腺癌NCI-H1650细胞系和大细胞肺癌NCI-H460细胞系中的抗肿瘤药效。我们进一步探讨了在缺氧和缺氧条件下NCI-H460细胞对吉非替尼的耐药性。所建立的复合膜夹心肺芯片可以模拟肺生理和病理微环境中更多的生化和生物物理因素，在肺肿瘤的个性化治疗中具有重要的应用价值。有望在临床诊断和药物筛选中发挥潜在作用。我们评估了吉非替尼在两种非小细胞肺癌细胞，即肺腺癌NCI-H1650细胞系和大细胞肺癌NCI-H460细胞系中的抗肿瘤药效。我们进一步探讨了在缺氧和缺氧条件下NCI-H460细胞对吉非替尼的耐药性。所建立的复合膜夹心肺芯片可以模拟肺生理和病理微环境中更多的生化和生物物理因素，在肺肿瘤的个性化治疗中具有重要的应用价值。有望在临床诊断和药物筛选中发挥潜在作用。我们评估了吉非替尼在两种非小细胞肺癌细胞，即肺腺癌NCI-H1650细胞系和大细胞肺癌NCI-H460细胞系中的抗肿瘤药效。我们进一步探讨了在缺氧和缺氧条件下NCI-H460细胞对吉非替尼的耐药性。所建立的复合膜夹心肺芯片可以模拟肺生理和病理微环境中更多的生化和生物物理因素，在肺肿瘤的个性化治疗中具有重要的应用价值。有望在临床诊断和药物筛选中发挥潜在作用。所建立的复合膜夹心肺芯片可以模拟肺生理和病理微环境中更多的生化和生物物理因素，在肺肿瘤的个性化治疗中具有重要的应用价值。有望在临床诊断和药物筛选中发挥潜在作用。所建立的复合膜夹心肺芯片可以模拟肺生理和病理微环境中更多的生化和生物物理因素，在肺肿瘤的个性化治疗中具有重要的应用价值。有望在临床诊断和药物筛选中发挥潜在作用。