Microphysiological systems modeling acute respiratory distress syndrome that capture mechanical force-induced injury-inflammation-repair.

• Type of Material: Article
• Authors: Hannah Viola, Georgia Institute of Technology; Jonathan Chang, Georgia Institute of Technology; Jocelyn Grunwell, Emory University; Louise Hecker, University of Arizona; Rabindra Tirouvanziam, Emory University; James B. Grotberg, University of Michigan; Shuichi Takayama, Emory University
• Language: English
• Date: 2019-12
• Publisher: AIP Publishing LLC
• Publication Version: Final Published Version
• Copyright Statement: © Author(s). CC BY 4.0
• Final Published Version (URL): http://dx.doi.org/10.1063/1.5111549
• Title of Journal or Parent Work: APL Bioengineering
• ISSN: 2473-2877
• Volume: 3
• Issue: 4
• Start Page: 041503
• End Page: 041503
• Grant/Funding Information: NSF Graduate Research Fellowship Program (No. 1650114).; Atlanta Pediatric Scholars Program (No. NICHD K12 HD072245).; Peer Reviewed Medical Research Program under Award No. W81XWH-17-1-0443; the Veterans Administration Health System Grant No. 1 I01 BX003919-01A1; and NIH Grant No. 1R41HL140741.; NIH (No. HL136141 to S.T. and J.B.G.; No. AG061687 to S.T. and L.H.; No. HL126603 to R.T.; No. 5T32EB006343-08 to H.V.).
• Keywords: ARDS; Mechanical ventilation; Inflammation; Microphysiological systems; Pulmonology; Repair; Lungs
• Research Categories: Health Sciences, Pathology; Engineering, Biomedical; Biology, Animal Physiology

Abstract

Complex in vitro models of the tissue microenvironment, termed microphysiological systems, have enormous potential to transform the process of discovering drugs and disease mechanisms. Such a paradigm shift is urgently needed in acute respiratory distress syndrome (ARDS), an acute lung condition with no successful therapies and a 40% mortality rate. Here, we consider how microphysiological systems could improve understanding of biological mechanisms driving ARDS and ultimately improve the success of therapies in clinical trials. We first discuss how microphysiological systems could explain the biological mechanisms underlying the segregation of ARDS patients into two clinically distinct phenotypes. Then, we contend that ARDS-mimetic microphysiological systems should recapitulate three critical aspects of the distal airway microenvironment, namely, mechanical force, inflammation, and fibrosis, and we review models that incorporate each of these aspects. Finally, we recognize the substantial challenges associated with combining inflammation, fibrosis, and/or mechanical force in microphysiological systems. Nevertheless, complex in vitro models are a novel paradigm for studying ARDS, and they could ultimately improve patient care.