Capturing the Onset of Bacterial Pulmonary Infection in Acini‐On‐Chips. Issue 9 (31st July 2019)

• Record Type: Journal Article
• Authors: Artzy‐Schnirman, Arbel; Zidan, Hikaia; Elias‐Kirma, Shani; Ben‐Porat, Lee; Tenenbaum‐Katan, Janna; Carius, Patrick; Fishler, Ramy; Schneider‐Daum, Nicole; Lehr, Claus‐Michael; Sznitman, Josué
• Is Part Of: Advanced biosystems. Volume 3:Issue 9(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-07-31
• Subjects: epithelial barrier -- in vitro assays -- microfluidics -- organ‐on‐chip -- pulmonary infection; Biological systems -- Periodicals; Biotechnology -- Periodicals; Bioengineering -- Periodicals; Biomedical engineering -- Periodicals; Biological Science Disciplines; Periodicals; Periodicals; 660.6
• DOI: 10.1002/adbi.201900026
• Languages: English
• ISSNs: 2366-7478

Abstract

Abstract: Bacterial invasion of the respiratory system leads to complex immune responses. In the deep alveolar regions, the first line of defense includes foremost the alveolar epithelium, the surfactant‐rich liquid lining, and alveolar macrophages. Typical in vitro models come short of mimicking the complexity of the airway environment in the onset of airway infection; among others, they neither capture the relevant anatomical features nor the physiological flows innate of the acinar milieu. Here, novel microfluidic‐based acini‐on‐chips that mimic more closely the native acinar airways at a true scale with an anatomically inspired, multigeneration alveolated tree are presented and an inhalation‐like maneuver is delivered. Composed of human alveolar epithelial lentivirus immortalized cells and macrophages‐like human THP‐1 cells at an air–liquid interface, the models maintain critically an epithelial barrier with immune function. To demonstrate, the usability and versatility of the platforms, a realistic inhalation exposure assay mimicking bacterial infection is recapitulated, whereby the alveolar epithelium is exposed to lipopolysaccharides droplets directly aerosolized and the innate immune response is assessed by monitoring the secretion of IL8 cytokines. These efforts underscore the potential to deliver advanced in vitro biosystems that can provide new insights into drug screening as well as acute and subacute toxicity assays. Abstract : A microfluidic‐based acinus‐on‐chip is presented that mimics the native acinar airways at real scale with an anatomically inspired alveolated tree. The acinus‐on‐chip is populated with human alveolar type‐1 and macrophages‐like human cells at an air–liquid interface. The usability and versatility of the in vitro platforms is demonstrated with a realistic inhalation exposure assay mimicking bacterial infection.