We describe the engineering design, computational modeling, and empirical performance of a moving air–liquid interface (MALI) bioreactor for the study of aerosol deposition on cells cultured on an elastic, porous membrane which mimics both air–liquid interface exposure conditions and mechanoelastic motion of lung tissue during breathing. The device consists of two chambers separated by a cell layer cultured on a porous, flexible membrane. The lower (basolateral) chamber is perfused with cell culture medium simulating blood circulation. The upper (apical) chamber representing the air compartment of the lung is interfaced to an aerosol generator and a pressure actuation system. By cycling the pressure in the apical chamber between 0 and 7 kPa, the membrane can mimic the periodic mechanical strain of the alveolar wall. Focusing on the engineering aspects of the system, we show that membrane strain can be monitored by measuring changes in pressure resulting from the movement of media in the basolateral chamber. Moreover, liquid aerosol deposition at a high dose delivery rate (>1 µl cm⁻² min⁻¹) is highly efficient (ca. 51.5%) and can be accurately modeled using finite element methods. Finally, we show that lung epithelial cells can be mechanically stimulated under air–liquid interface and stretch‐conditions without loss of viability. The MALI bioreactor could be used to study the effects of aerosol on alveolar cells cultured at the air–liquid interface in a biodynamic environment or for toxicological or therapeutic applications.

中文翻译：

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气溶胶输送肺泡界面动态体外拉伸模型的开发

我们描述了移动气液界面 (MALI) 生物反应器的工程设计、计算建模和经验性能，用于研究在模拟气液界面暴露条件和机械弹性运动的弹性多孔膜上培养的细胞上的气溶胶沉积呼吸时肺组织。该装置由在多孔柔性膜上培养的细胞层分隔的两个室组成。下部（基底外侧）室灌注有模拟血液循环的细胞培养基。代表肺气室的上（心尖）腔与气溶胶发生器和压力驱动系统相连。通过在 0 到 7 kPa 之间循环调节心尖室中的压力，该膜可以模拟肺泡壁的周期性机械应变。专注于系统的工程方面，我们表明可以通过测量基底外侧室中介质运动引起的压力变化来监测膜应变。此外，液体气溶胶沉积在高剂量输送率 (>1 µl cm^-2  min ^-1 ) 是高效的（约 51.5%）并且可以使用有限元方法准确建模。最后，我们表明肺上皮细胞可以在气液界面和拉伸条件下被机械刺激而不会丧失活力。MALI 生物反应器可用于研究气溶胶对生物动力环境中气液界面培养的肺泡细胞的影响，或用于毒理学或治疗应用。