Developing platforms for tissue engineering of the airways

Ramis, Jopeth (2020) Developing platforms for tissue engineering of the airways. PhD thesis, University of Nottingham.

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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.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Buttery, Lee
Rose, Felicity
Tatler, Amanda
Keywords: airway dynamics, respiratory tract, epithelial cells, tissue engineering
Subjects: Q Science > QP Physiology > QP1 Physiology (General) including influence of the environment
R Medicine > R Medicine (General) > R855 Medical technology. Biomedical engineering. Electronics
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 60282
Depositing User: Ramis, Jopeth
Date Deposited: 11 Oct 2023 13:30
Last Modified: 11 Oct 2023 13:30

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