A multiphase fluidic platform for studying ventilator-induced injury of the pulmonary epithelial barrier

Abstract

Mechanical ventilation has been a critical part of basic life support for many years, with almost one-third of all patients in the intensive care unit requiring the aid. However studies over the past two decades have indicated that ventilators have the potential to cause or aggravate pulmonary injury. The lung with its anatomically complex architecture and unique amalgam of cell types and interfaces is very difficult to replicate in vitro. This study is focused on mimicking the distal unit of the alveolus in developing an analytical platform for evaluating cellular interactions and response to mechanostimulation. The prototype developed incorporates the ability to expose alveolar cells to sustained periods of supra-physiological pressure when cultured at an air–liquid interface with constant air-flow on the apical side and medium replenishment on basolateral surfaces. The in vitro evaluation of the alveolar, A549 and H441, cells indicated disruption of the cell layer integrity in response to sustained pressure application. The results indicate a magnitude- and duration-dependent response among both the cell types.