| Cardiovascular disease affects over 82 million Americans, of which myocardial infarction (MI) and subsequent heart failure (HF) patients are a major subset. As a result, the development of new therapies for the prevention of HF is a rising clinical need. Several injectable materials have been shown to preserve or improve cardiac function as well as prevent or slow LV remodeling post-MI. However, the mechanism by which these materials influence cardiac function is not fully understood.;The objective of this dissertation is to investigate whether it is the structural support, bioactivity and/or degradation of these biomaterials that leads to the beneficial effects seen with injectable materials used for treatment of MI. Furthermore, the impact of intramyocardial injection of these biomaterials on cardiac electrophysiology is assessed. Herein, we examined how passive structural enhancement of the LV wall by a permanent increase in wall thickness affected cardiac function post-MI using a bio-inert, non-degradable synthetic poly(ethylene) glycol (PEG) polymer. Contrary to popular opinion, passive structural reinforcement alone was insufficient to prevent post-MI remodeling.;As the next step in understanding the mechanism of action of injectable materials, a bio-inert synthetic degradable PEG was injected into the infarct site. Injection of degradable material resulted in a decline in cardiac function and undesirable changes in LV geometry similar to that of the non-degradable PEG. Thus, establishing that the ability for cell adherence and protein absorption may play an influential role in the improvement or preservation of cardiac function.;While most degradable bioactive materials have improved cardiac function, there remain concerns that biomaterial injection may create a substrate for arrhythmia. Optical mapping was utilized to assess the effects of biomaterial injection and spread on cardiac electrophysiology. Injection of a bulk biomaterial in myocardium may create a substrate for arrhythmia by causing activation delays and local heterogeneities in electrophysiological parameters at the site of injection. Therefore, delivery or spread of a material into viable or border zone myocardium may have deleterious effects, establishing site of delivery as an important factor of biomaterial therapies for MI treatment.;This work provides the field of cardiac tissue engineering guidelines for the future design and delivery of biomaterials, and moreover imparts a deeper understanding of the properties of biomaterials necessary to prevent post-MI negative remodeling and subsequent HF. |
