Micro/Nano Scale Modeling of Cellular injury and Inflammation in the Alveolar Microenvironment during Mechanical Ventilation

Bibliographic Details
Main Author:	Higuita-Castro, Natalia
Language:	English
Published:	The Ohio State University / OhioLINK 2013
Subjects:	Biomedical Engineering
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=osu1385516912

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-osu13855169122021-08-03T06:20:37Z Micro/Nano Scale Modeling of Cellular injury and Inflammation in the Alveolar Microenvironment during Mechanical Ventilation Higuita-Castro, Natalia Biomedical Engineering Patients suffering from acute lung injury (ALI) are unable to sufficiently oxygenate via normal respiration and often require mechanical ventilation to achieve adequate gas exchange. Although critical for patient survival, the reopening of collapsed airways during mechanical ventilation exacerbates the preexisting lung injury and may lead to ventilator-induced lung injury (VILI). Previous studies have used in vitro systems that cultured epithelial cells on glass substrates to demonstrate that factors such as cytoskeletal structure and reopening velocity can influence the degree of cell injury during airway reopening. However, this type of flat rigid model does not account for the complex microstructure of the extracellular matrix (ECM) present in the lung. Specifically, the lung ECM is compliant and is composed of specific proteins that form a fibrous micro/nanostructure and remodeling of this structure plays an important role in several lung disorders (e.g. fibrosis and emphysema). In this dissertation we studied how intrinsic properties of the lung tissue (e.g. compliance of the basement membrane, topography, and heterotypic cell-cell interactions) influence the injury of lung epithelial cells during mechanical ventilation. For this purpose we have developed two in vitro systems: our first model uses polyacrylamide gels with different rigidities to simulate diverse lung tissue stiffness, and our second model closely resembles the alveolar-capillary microenvironment by allowing the co-culture of epithelial and endothelial cells on a compliant nano-fibrous polymeric substrate. Our results highlight the importance of implementing biomimetic systems to study the pathological mechanisms responsible for VILI as well as other diseases involving abnormal ECM morphology such as fibrosis.We also explored the potential pharmaco-protective effect of Rho-pathway inhibitors on lung epithelial cells during airway reopening, which induce lower cell injury, detachment, and inflammation. Similarly, we explored the role of miR-146a as a mechanosensitive biomarker of mechanically-induced inflammation and as a negative regulator of ventilation induced inflammation. Finally, at the end of this dissertation we described a simple and versatile microfabrication protocol that could potentially be used to obtain microparticles for delivery of active compounds into the lung for treatment of VILI. 2013 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1385516912 http://rave.ohiolink.edu/etdc/view?acc_num=osu1385516912 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Biomedical Engineering
spellingShingle	Biomedical Engineering Higuita-Castro, Natalia Micro/Nano Scale Modeling of Cellular injury and Inflammation in the Alveolar Microenvironment during Mechanical Ventilation
author	Higuita-Castro, Natalia
author_facet	Higuita-Castro, Natalia
author_sort	Higuita-Castro, Natalia
title	Micro/Nano Scale Modeling of Cellular injury and Inflammation in the Alveolar Microenvironment during Mechanical Ventilation
title_short	Micro/Nano Scale Modeling of Cellular injury and Inflammation in the Alveolar Microenvironment during Mechanical Ventilation
title_full	Micro/Nano Scale Modeling of Cellular injury and Inflammation in the Alveolar Microenvironment during Mechanical Ventilation
title_fullStr	Micro/Nano Scale Modeling of Cellular injury and Inflammation in the Alveolar Microenvironment during Mechanical Ventilation
title_full_unstemmed	Micro/Nano Scale Modeling of Cellular injury and Inflammation in the Alveolar Microenvironment during Mechanical Ventilation
title_sort	micro/nano scale modeling of cellular injury and inflammation in the alveolar microenvironment during mechanical ventilation
publisher	The Ohio State University / OhioLINK
publishDate	2013
url	http://rave.ohiolink.edu/etdc/view?acc_num=osu1385516912
work_keys_str_mv	AT higuitacastronatalia micronanoscalemodelingofcellularinjuryandinflammationinthealveolarmicroenvironmentduringmechanicalventilation
_version_	1719435047080034304

Micro/Nano Scale Modeling of Cellular injury and Inflammation in the Alveolar Microenvironment during Mechanical Ventilation

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