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

APL Bioengineering - Tập 3 Số 4 - 2019
Hannah Viola1,2, Jonathan Chang3, Jocelyn R. Grunwell4, Louise Hecker5,6, Rabindra Tirouvanziam7,8, James B. Grotberg9, Shuichi Takayama2,3
1School of Chemical and Biomolecular Engineering, Georgia Institute of Technology 1 , Atlanta, Georgia 30332, USA
2The Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology 2 , Atlanta, Georgia 30332, USA
3Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory School of Medicine 3 , Atlanta, Georgia 30332, USA
4Department of Pediatrics, Division of Critical Care Medicine, Children's Healthcare of Atlanta at Egleston, Emory University School of Medicine 4 , Atlanta, Georgia 30322, USA
5Division of Pulmonary, Allergy and Critical Care and Sleep Medicine, University of Arizona, Tucson, Arizona 85724, USA and Southern Arizona Veterans Affairs Health Care System, Tucson, Arizona 85723, USA
6Southern Arizona Veterans Affairs Health Care System 5 , Tucson, Arizona 85724, USA and , Tucson, Arizona 85723, USA
7Center for CF and Airways Disease Research, Children's Healthcare of Atlanta 6 , Atlanta, Georgia 30322, USA and , Atlanta, Georgia 30322, USA
8Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA and Center for CF and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, Georgia 30322, USA
9Department of Biomedical Engineering, University of Michigan 7 , Ann Arbor, Michigan 48109, USA

Tóm tắt

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.

Từ khóa


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