Abstract:
The gas exchange units of the lung, the alveoli, are mechanically active and undergo cyclic deformation during breathing. The epithelial cells that line the alveoli contribute to lung function by reducing surface tension via surfactant secretion, which is highly influenced by the breathing-associated mechanical cues. These spatially heterogeneous mechanical cues have been linked to several physiological and pathophysiological states. Here, we describe the development of a microfluidically assisted lung cell culture model that incorporates heterogeneous cyclic stretching to mimic alveolar respiratory motions. Employing this device, we have examined the effects of respiratory biomechanics (associated with breathing-like movements) and strain heterogeneity on alveolar epithelial cell functions. Furthermore, we have assessed the potential application of this platform to model altered matrix compliance associated with lung pathogenesis and ventilator-induced lung injury. Lung microphysiological platforms incorporating human cells and dynamic biomechanics could serve as an important tool to delineate the role of alveolar micromechanics in physiological and pathological outcomes in the lung.
摘要:
肺的气体交换单元,肺泡,是机械活动的,并在呼吸过程中经历循环变形。排列肺泡的上皮细胞通过表面活性剂分泌降低表面张力来促进肺功能,受到与呼吸相关的机械提示的高度影响。这些空间异质的机械线索与几种生理和病理生理状态有关。这里,我们描述了微流体辅助肺细胞培养模型的发展,该模型结合了异质循环拉伸来模拟肺泡呼吸运动。使用这个设备,我们研究了呼吸生物力学(与呼吸样运动相关)和应变异质性对肺泡上皮细胞功能的影响.此外,我们评估了该平台在模拟与肺发病机制和呼吸机诱导的肺损伤相关的基质顺应性改变方面的潜在应用.结合人体细胞和动态生物力学的肺微生理平台可以作为描绘肺泡微力学在肺生理和病理结果中的作用的重要工具。