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

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.

One‐Step Formation of Protein‐Based Tubular Structures for Functional Devices and Tissues

“…Their walls consist of extracellular matrix (ECM) proteins and resident cells and are either stretched or compressed. As a result, the fluid containing luminal areas may increase during dilation, decrease during constriction, [ 2 ] completely impede luminal flow during collapse, [ 3 ] or promote flow by peristalsis. The walls are lined with tight barrier layers of either endothelial or epithelial cells that respond to mechanosensory and biomolecular cues, regulating the passage of molecules, particles, and cells.…”

Regeneration of lung epithelial cells by Fullerene C60nanoformulation: A possible treatment strategy for acute respiratory distress syndrome (ARDS)

“…For initial drug development, primary lung epithelial cells, or lung epithelial cell lines can be used to simulate ARDS condition. 14 Since one of the leading outcomes of ARDS is apoptosis of alveolar epithelial cells, 15 the end-point of our study was to obtain high cell viability in two experimental Please do not adjust margins Please do not adjust margins models of cellular damage. Here we have shown that the proliferative Fullerene nanoformulation has the potential to increase cell viability after induced cell damage by toxic nanoparticles (FT30) or hydrogen peroxide.…”

The effect of viscoelasticity in an airway closure model

“…For these reasons, modelling airway closure must take into account pathologies which induce accumulation of liquid due to infections or edema, hypersecretion of mucus and surfactant deficiency or dysfunction. Typical lung diseases are pneumonia (Gunther et al 1996), asthma (Veen et al 2000), bronchiolitis (Dargaville, South & Mcdougall 1996), chronic obstructive pulmonary disease (known as COPD; Guerin et al (1997)), cystic fibrosis (Griese et al 2004) and acute respiratory distress syndrome (known as ARDS; Viola et al (2019)). For literature reviews of respiratory airway closure, liquid plug propagation and rupture, we refer to Grotberg (1994Grotberg ( , 2001Grotberg ( , 2011.…”

“…2004) and acute respiratory distress syndrome (known as ARDS; Viola et al. (2019)). For literature reviews of respiratory airway closure, liquid plug propagation and rupture, we refer to Grotberg (1994, 2001, 2011).…”