Development of an Injectable Hydrogel Scaffold for Cardiac Tissue Engineering
File(s)
Andre Chow PhD Thesis
Author(s)
Chow, Andre
Type
Thesis
Abstract
Cardiac failure following myocardial infarction is an important global health issue and a leading cause of morbidity and mortality worldwide. Current treatments do not address the underlying problem of massive cardiomyocyte loss. New tissue engineering strategies may be capable of regenerating or repairing cardiac tissue.
The aim of this thesis was to design a cardiac tissue engineering strategy including aspects of biomaterials, cells and soluble factors.
For the biomaterial arm a polyethylene glycol (PEG) based hydrogel was designed to match the mechanical properties of myocardial tissue whilst remaining degradable and with the capability of supporting live cells. Injection of the hydrogel into the myocardium demonstrated no significant adverse effects using a Langendorff and in vivo model. Induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) were used as the cellular component of the strategy, with Erythropoietin (Epo) demonstrating protective effects in an in vitro model of cellular injury.
A model of rat myocardial infarction was used. The left anterior descending artery was ligated in vivo to create an infarction. Combinations of hydrogel, iPS-CM, and Epo were injected into the infarct border zones with follow up for 8-10 weeks. A combination of hydrogel, iPS-CM and Epo demonstrated significantly more muscularisation and thickness of the infarct zone, with improvements noted in ejection fraction over infarct controls.
These results support a multidisciplinary approach to cardiac tissue engineering.
The aim of this thesis was to design a cardiac tissue engineering strategy including aspects of biomaterials, cells and soluble factors.
For the biomaterial arm a polyethylene glycol (PEG) based hydrogel was designed to match the mechanical properties of myocardial tissue whilst remaining degradable and with the capability of supporting live cells. Injection of the hydrogel into the myocardium demonstrated no significant adverse effects using a Langendorff and in vivo model. Induced pluripotent stem cell-derived cardiomyocytes (iPS-CM) were used as the cellular component of the strategy, with Erythropoietin (Epo) demonstrating protective effects in an in vitro model of cellular injury.
A model of rat myocardial infarction was used. The left anterior descending artery was ligated in vivo to create an infarction. Combinations of hydrogel, iPS-CM, and Epo were injected into the infarct border zones with follow up for 8-10 weeks. A combination of hydrogel, iPS-CM and Epo demonstrated significantly more muscularisation and thickness of the infarct zone, with improvements noted in ejection fraction over infarct controls.
These results support a multidisciplinary approach to cardiac tissue engineering.
Version
Open Access
Date Issued
2013-10
Date Awarded
2014-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Athanasiou, Thanos
Stevens, Molly
Harding, Sian
Sponsor
Wellcome Trust (London, England)
Grant Number
p35357
Publisher Department
Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)