Basia Gabela-Zuniga, Vasudha C. Shukla, Christopher Bobba, Natalia Higuita-Castro, Heather M. Powell, Joshua A. Englert and Samir N. Ghadiali
{"title":"用于研究机械通气损伤效应的微尺度人源化芯片呼吸机","authors":"Basia Gabela-Zuniga, Vasudha C. Shukla, Christopher Bobba, Natalia Higuita-Castro, Heather M. Powell, Joshua A. Englert and Samir N. Ghadiali","doi":"10.1039/D4LC00143E","DOIUrl":null,"url":null,"abstract":"<p >Patients with compromised respiratory function frequently require mechanical ventilation to survive. Unfortunately, non-uniform ventilation of injured lungs generates complex mechanical forces that lead to ventilator induced lung injury (VILI). Although investigators have developed lung-on-a-chip systems to simulate normal respiration, modeling the complex mechanics of VILI as well as the subsequent recovery phase is a challenge. Here we present a novel humanized <em>in vitro</em> ventilator-on-a-chip (VOC) model of the lung microenvironment that simulates the different types of injurious forces generated in the lung during mechanical ventilation. We used transepithelial/endothelial electrical impedance measurements to investigate how individual and simultaneous application of mechanical forces alters real-time changes in barrier integrity during and after injury. We find that compressive stress (<em>i.e.</em> barotrauma) does not significantly alter barrier integrity while over-distention (20% cyclic radial strain, volutrauma) results in decreased barrier integrity that quickly recovers upon removal of mechanical stress. Conversely, surface tension forces generated during airway reopening (atelectrauma), result in a rapid loss of barrier integrity with a delayed recovery relative to volutrauma. Simultaneous application of cyclic stretching (volutrauma) and airway reopening (atelectrauma), indicates that the surface tension forces associated with reopening fluid-occluded lung regions are the primary driver of barrier disruption. Thus, our novel VOC system can monitor the effects of different types of injurious forces on barrier disruption and recovery in real-time and can be used to interogate the biomechanical mechanisms of VILI.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/lc/d4lc00143e?page=search","citationCount":"0","resultStr":"{\"title\":\"A micro-scale humanized ventilator-on-a-chip to examine the injurious effects of mechanical ventilation†\",\"authors\":\"Basia Gabela-Zuniga, Vasudha C. Shukla, Christopher Bobba, Natalia Higuita-Castro, Heather M. Powell, Joshua A. Englert and Samir N. Ghadiali\",\"doi\":\"10.1039/D4LC00143E\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Patients with compromised respiratory function frequently require mechanical ventilation to survive. Unfortunately, non-uniform ventilation of injured lungs generates complex mechanical forces that lead to ventilator induced lung injury (VILI). Although investigators have developed lung-on-a-chip systems to simulate normal respiration, modeling the complex mechanics of VILI as well as the subsequent recovery phase is a challenge. Here we present a novel humanized <em>in vitro</em> ventilator-on-a-chip (VOC) model of the lung microenvironment that simulates the different types of injurious forces generated in the lung during mechanical ventilation. We used transepithelial/endothelial electrical impedance measurements to investigate how individual and simultaneous application of mechanical forces alters real-time changes in barrier integrity during and after injury. We find that compressive stress (<em>i.e.</em> barotrauma) does not significantly alter barrier integrity while over-distention (20% cyclic radial strain, volutrauma) results in decreased barrier integrity that quickly recovers upon removal of mechanical stress. Conversely, surface tension forces generated during airway reopening (atelectrauma), result in a rapid loss of barrier integrity with a delayed recovery relative to volutrauma. Simultaneous application of cyclic stretching (volutrauma) and airway reopening (atelectrauma), indicates that the surface tension forces associated with reopening fluid-occluded lung regions are the primary driver of barrier disruption. 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A micro-scale humanized ventilator-on-a-chip to examine the injurious effects of mechanical ventilation†
Patients with compromised respiratory function frequently require mechanical ventilation to survive. Unfortunately, non-uniform ventilation of injured lungs generates complex mechanical forces that lead to ventilator induced lung injury (VILI). Although investigators have developed lung-on-a-chip systems to simulate normal respiration, modeling the complex mechanics of VILI as well as the subsequent recovery phase is a challenge. Here we present a novel humanized in vitro ventilator-on-a-chip (VOC) model of the lung microenvironment that simulates the different types of injurious forces generated in the lung during mechanical ventilation. We used transepithelial/endothelial electrical impedance measurements to investigate how individual and simultaneous application of mechanical forces alters real-time changes in barrier integrity during and after injury. We find that compressive stress (i.e. barotrauma) does not significantly alter barrier integrity while over-distention (20% cyclic radial strain, volutrauma) results in decreased barrier integrity that quickly recovers upon removal of mechanical stress. Conversely, surface tension forces generated during airway reopening (atelectrauma), result in a rapid loss of barrier integrity with a delayed recovery relative to volutrauma. Simultaneous application of cyclic stretching (volutrauma) and airway reopening (atelectrauma), indicates that the surface tension forces associated with reopening fluid-occluded lung regions are the primary driver of barrier disruption. Thus, our novel VOC system can monitor the effects of different types of injurious forces on barrier disruption and recovery in real-time and can be used to interogate the biomechanical mechanisms of VILI.
期刊介绍:
Lab on a Chip is the premiere journal that publishes cutting-edge research in the field of miniaturization. By their very nature, microfluidic/nanofluidic/miniaturized systems are at the intersection of disciplines, spanning fundamental research to high-end application, which is reflected by the broad readership of the journal. Lab on a Chip publishes two types of papers on original research: full-length research papers and communications. Papers should demonstrate innovations, which can come from technical advancements or applications addressing pressing needs in globally important areas. The journal also publishes Comments, Reviews, and Perspectives.