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Mechanobiology and Finite Element Analysis of Cellular Injury During Microbubble Flows

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Cellular and Biomolecular Mechanics and Mechanobiology

Part of the book series: Studies in Mechanobiology, Tissue Engineering and Biomaterials ((SMTEB,volume 4))

Abstract

Microbubble flows and their effects on the lung epithelium are a key component of the acute respiratory distress syndrome (ARDS), a condition commonly treated by mechanical ventilation. Recent clinical evidence suggests that it may be difficult to choose a ventilation protocol that completely eliminates the damaging mechanical forces experienced by the epithelium. In this chapter, we describe our research group’s use of both experimental and computational techniques to investigate how strategic changes in the cells’ cytotskeletal structure and mechanical properties can be used to alter the way these cells respond to the hydrodynamic forces generated during microbubble flows. First, we present experimental data which describes the relationship between hydrodynamic conditions and cell necrosis during microbubble flows. The experimental results were then used to develop validated finite element models that provided quantitative information about cellular deformation during microbubble flows. These models suggested several pharmaco-protective strategies for reducing epithelial cell (EpC) injury by altering cell mechanics and these predictions were confirmed by a new set of clinically relevant experimental studies. We also discuss the future potential for combined experimental and computational approaches to treating lung injury and how these techniques may help elucidate the mechanotransduction of microbubble forces into inflammatory signaling and other processes that contribute to the pathology of ARDS.

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Abbreviations

ALI:

Acute lung injury

ARDS:

Acute respiratory distress syndrome

EpC:

Epithelial cells

Mβ-CD:

Methyl-β-cyclodextrin

PEEP:

Positive end expiratory pressure

VILI:

Ventilator-induced lung injury

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Authors and Affiliations

  1. Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA

    Samir N. Ghadiali

  2. Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, 43210, USA

    Samir N. Ghadiali

  3. Medical Engineering Design and Innovation Centre, Cork Institute of Technology, Bishopstown, Co, Cork, Ireland

    Hannah L. Dailey

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  1. Samir N. Ghadiali
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Correspondence to Samir N. Ghadiali .

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  1. Fac. Engineering, Dept. Biomedical Engineering, Tel Aviv University, Ramat Aviv, 69978, Israel

    Amit Gefen

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Ghadiali, S.N., Dailey, H.L. (2010). Mechanobiology and Finite Element Analysis of Cellular Injury During Microbubble Flows. In: Gefen, A. (eds) Cellular and Biomolecular Mechanics and Mechanobiology. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8415_2010_25

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