Development of an Injectable Hydrogel Scaffold for Cardiac Tissue Engineering

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.