Traditional in vitro and in vivo models for inhalation toxicology studies often fail to replicate the anatomical and physiological conditions of the human lung. This limitation hinders our understanding of intrapulmonary exposures and their related health effects. To address this gap, we developed a ventilated artificial lung system that replicates human inhalation exposures in four key aspects: (1) facilitating continuous breathing with adjustable respiratory parameters; (2) distributing inhaled aerosols through transitional airflow fields in 3D-printed airway structures, which enables size-dependent particle deposition; (3) duplicating the warm and humid lung environment to promote inhaled aerosol dynamics, such as hygroscopic growth; and (4) supporting the cultivation of human airway epithelium for aerosol exposure and toxicological analyses. As a proof-of-concept application, we exposed human bronchial epithelial cells to electronic cigarette aerosols in the system. Our results show that electronic cigarette particles undergo significant hygroscopic growth within the artificial lung, leading to a 19% greater deposition dose compared to data collected at room temperature and relative humidity. Additionally, short-term exposure altered epithelial production of the chemokine Fractalkine in a nicotine-dependent manner, but no acute toxic effects were observed. This artificial lung system provides a more physiologically relevant in vitro model for studying inhalation exposures.

中文翻译：

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用于人体吸入暴露研究的通气三维人工肺系统


用于吸入毒理学研究的传统体外和体内模型通常无法复制人体肺的解剖和生理状况。这种局限性阻碍了我们对肺内暴露及其相关健康影响的理解。为了解决这一差距，我们开发了一种通气人工肺系统，该系统在四个关键方面复制人类吸入暴露：（1） 通过可调节的呼吸参数促进连续呼吸;（2） 通过 3D 打印气道结构中的过渡气流场分配吸入的气溶胶，从而实现与尺寸相关的颗粒沉积;（3） 复制温暖潮湿的肺部环境，以促进吸入气溶胶动力学，如吸湿生长;（4） 支持培养人气道上皮用于气溶胶暴露和毒理学分析。作为概念验证应用，我们将人支气管上皮细胞暴露在系统中的电子烟气溶胶中。我们的结果表明，电子烟颗粒在人工肺内经历显着的吸湿性生长，与在室温和相对湿度下收集的数据相比，沉积剂量增加了 19%。此外，短期暴露以尼古丁依赖性方式改变了趋化因子 Fractalkine 的上皮产生，但没有观察到急性毒性作用。这种人工肺系统为研究吸入暴露提供了更具生理相关性的体外模型。