Developing platforms for tissue engineering of the airways

Understanding airway dynamics has been under rigorous study for past decades due to its implication in health and disease, where in vitro, in vivo and human subjects are continuously being investigated for causation of diseased pathways. However, limitations arise as the variability in the models ar...

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Main Author: Ramis, Jopeth
Format: Thesis (University of Nottingham only)
Language:English
Published: 2020
Subjects:
Online Access:https://eprints.nottingham.ac.uk/60282/
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author Ramis, Jopeth
author_facet Ramis, Jopeth
author_sort Ramis, Jopeth
building Nottingham Research Data Repository
collection Online Access
description Understanding airway dynamics has been under rigorous study for past decades due to its implication in health and disease, where in vitro, in vivo and human subjects are continuously being investigated for causation of diseased pathways. However, limitations arise as the variability in the models are unavoidable, and many factors such as cell microenvironments are usually uncontrollable. To surpass this problem, tissue engineering offers a platform to create systematically a controlled environment for the cells to grow. This discipline is used in order to observe cause-and effect scenarios that elucidates physiological processes and pathological dysregulation within the biology of interest. A platform that allows factors to be tuned to mimic biological conditions of the airways will be truly helpful in unlocking information on how airway cells behave and respond to their environment. In this work, the tissue engineering central dogma of cells, biomaterials and bioreactor was utilised to setup an observable environment for the cells to be studied. Specifically, airway smooth muscle and epithelial cells were cultured on biomimetic scaffolds that can be tuned mechanically and chemically. Airway smooth muscle cells cultured on stiffening scaffolds showed an asthma-like phenotype, displaying elevated marker for contractility, cell size, and proliferation capacity. For the airway epithelium, proliferation was also increased in increasing matrix stiffness, and augmenting the scaffold with a functional group similar to the native epithelium further supported its growth. Lastly, a double-chambered bioreactor was designed to support culture of the airways, in which its evaluation and performance was assessed computationally and experimentally to obtain optimum parameters for airway culture. It is hoped that the platforms developed in this thesis for the tissue engineering of the airways will elucidate pathways on how disease processes occur without the need for in vivo models. Such model may be used not just on understanding of the biology of the airways, but also a platform to evaluate therapeutic options for alleviation of chronic and lethal airway diseases.
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spelling nottingham-602822025-02-28T14:51:56Z https://eprints.nottingham.ac.uk/60282/ Developing platforms for tissue engineering of the airways Ramis, Jopeth Understanding airway dynamics has been under rigorous study for past decades due to its implication in health and disease, where in vitro, in vivo and human subjects are continuously being investigated for causation of diseased pathways. However, limitations arise as the variability in the models are unavoidable, and many factors such as cell microenvironments are usually uncontrollable. To surpass this problem, tissue engineering offers a platform to create systematically a controlled environment for the cells to grow. This discipline is used in order to observe cause-and effect scenarios that elucidates physiological processes and pathological dysregulation within the biology of interest. A platform that allows factors to be tuned to mimic biological conditions of the airways will be truly helpful in unlocking information on how airway cells behave and respond to their environment. In this work, the tissue engineering central dogma of cells, biomaterials and bioreactor was utilised to setup an observable environment for the cells to be studied. Specifically, airway smooth muscle and epithelial cells were cultured on biomimetic scaffolds that can be tuned mechanically and chemically. Airway smooth muscle cells cultured on stiffening scaffolds showed an asthma-like phenotype, displaying elevated marker for contractility, cell size, and proliferation capacity. For the airway epithelium, proliferation was also increased in increasing matrix stiffness, and augmenting the scaffold with a functional group similar to the native epithelium further supported its growth. Lastly, a double-chambered bioreactor was designed to support culture of the airways, in which its evaluation and performance was assessed computationally and experimentally to obtain optimum parameters for airway culture. It is hoped that the platforms developed in this thesis for the tissue engineering of the airways will elucidate pathways on how disease processes occur without the need for in vivo models. Such model may be used not just on understanding of the biology of the airways, but also a platform to evaluate therapeutic options for alleviation of chronic and lethal airway diseases. 2020-07-24 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/60282/1/Thesis%20Ramis%202019%20Final%20with%20changes%20v2.0.pdf Ramis, Jopeth (2020) Developing platforms for tissue engineering of the airways. PhD thesis, University of Nottingham. airway dynamics respiratory tract epithelial cells tissue engineering
spellingShingle airway dynamics
respiratory tract
epithelial cells
tissue engineering
Ramis, Jopeth
Developing platforms for tissue engineering of the airways
title Developing platforms for tissue engineering of the airways
title_full Developing platforms for tissue engineering of the airways
title_fullStr Developing platforms for tissue engineering of the airways
title_full_unstemmed Developing platforms for tissue engineering of the airways
title_short Developing platforms for tissue engineering of the airways
title_sort developing platforms for tissue engineering of the airways
topic airway dynamics
respiratory tract
epithelial cells
tissue engineering
url https://eprints.nottingham.ac.uk/60282/