Role of extracellular environment in mechanical properties of human cardiac fibroblasts and myofibroblasts
type: CreativeWork
description: Acute MI results in adverse remodelling of the myocardium, eventually leading to contractile dysfunction and chronic heart failure. Collectively, the formation of fibrotic scar tissue in the left ventricle inhibits its contractile function and leads to a cardiac output loss. Cardiac fibroblast and myofibroblast cells are integral in the remodelling of injured tissue and are the most anticipated therapeutic target for cardiac fibrosis. To date, there is no anti-fibrotic therapy, which we argue, is due to the lack of knowledge on the functionality of the cardiac fibroblast. It was hypothesised that a change in stiffness of the remodelling extracellular environment associated with fibrosis leads to a change of the mechanical properties and contractile forces of cardiac fibroblasts and myofibroblasts. Hence, this dissertation aimed to investigate the effects of extracellular stiffness on mechanical properties of cardiac fibroblasts and myofibroblasts using engineered in vitro microenvironments with tuneable physical properties. Polyethylene Glycol (PEG) hydrogels offer ideal properties to serve as an extracellular matrix (ECM) mimicking biomaterial. Different techniques of mechanical characterisation used in this study established that the elastic modulus of 20 kDa 8-arm PEG-VS hydrogel crosslinked with dithiothreitol (DTT) reagent, is directly proportional to the concentration of PEG precursor used to form the material. Rheological measurements indicated an elastic shear modulus of 500 ± 13 Pa and 2721 ± 39 Pa for PEG gels of 4% (m/v) and 10% (m/v), respectively. Specialised micro-indentation and uniaxial tensile testing found PEG gels of 7%, 10%, 14% and 18% concentration to have elastic moduli of 42.0 ± 2.8 kPa, 65.3 ±8.0 kPa, 78.2 ± 8.4 kPa, and 121.5 ± 11.9 kPa, respectively. The volumetric swelling ratio was shown to be inversely proportional to the precursor concentration. The addition of cell adhesion proteins, such as RGD peptides, resulted in a decrease in the…
abstract: Acute MI results in adverse remodelling of the myocardium, eventually leading to contractile dysfunction and chronic heart failure. Collectively, the formation of fibrotic scar tissue in the left ventricle inhibits its contractile function and leads to a cardiac output loss. Cardiac fibroblast and myofibroblast cells are integral in the remodelling of injured tissue and are the most anticipated therapeutic target for cardiac fibrosis. To date, there is no anti-fibrotic therapy, which we argue, is due to the lack of knowledge on the functionality of the cardiac fibroblast. It was hypothesised that a change in stiffness of the remodelling extracellular environment associated with fibrosis leads to a change of the mechanical properties and contractile forces of cardiac fibroblasts and myofibroblasts. Hence, this dissertation aimed to investigate the effects of extracellular stiffness on mechanical properties of cardiac fibroblasts and myofibroblasts using engineered in vitro microenvironments with tuneable physical properties. Polyethylene Glycol (PEG) hydrogels offer ideal properties to serve as an extracellular matrix (ECM) mimicking biomaterial. Different techniques of mechanical characterisation used in this study established that the elastic modulus of 20 kDa 8-arm PEG-VS hydrogel crosslinked with dithiothreitol (DTT) reagent, is directly proportional to the concentration of PEG precursor used to form the material. Rheological measurements indicated an elastic shear modulus of 500 ± 13 Pa and 2721 ± 39 Pa for PEG gels of 4% (m/v) and 10% (m/v), respectively. Specialised micro-indentation and uniaxial tensile testing found PEG gels of 7%, 10%, 14% and 18% concentration to have elastic moduli of 42.0 ± 2.8 kPa, 65.3 ±8.0 kPa, 78.2 ± 8.4 kPa, and 121.5 ± 11.9 kPa, respectively. The volumetric swelling ratio was shown to be inversely proportional to the precursor concentration. The addition of cell adhesion proteins, such as RGD peptides, resulted in a decrease in the…
author: Haasbroek, Pieter Daniël
keywords: Biomedical Engineering
date published: 2021
date modified: 2026-07-22T22:22:43Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Human Biology

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11427/36885