Abstract:
Cardiovascular disease is the leading cause of death for both men and women worldwide. Despite advances in post-infarction treatment, heart failure that develops after the heart attack still remains a major cause of death. Current treatments focus on supporting the healthy tissue following a heart attack, but do not actively prevent the degradation of the myocardial tissue that is characteristic of a typical infarction. Cardiovascular myocytes are unable to reenter the cell cycle and replicate, meaning that any myocardial tissue death will be replaced with non-contractile scar tissue. The decrease in overall function of the heart tissues leads to overcompensation of the remaining heart muscles. We hypothesize that a patch encapsulating stem cells can be placed directly on the heart surface and can generate enough beneficial growth factors to help prevent the degredation of the cardiac tissue and allow the heart to maintain its post-infarction function and efficiency.
Hydrogel patches composed of a combination of PEDGA and MA have been shown to support fibroblast proliferation and secrete VEGF into culture media. Furthermore, factors that are secreted by the patch have shown to initiate neovascularization in egg membrane assays. With possible beneficial properties shown in vitro, an in vivo approach can be taken to test the efficacy and possible treatment of ischemia in the heart. We have adopted a mouse myocardial infarction model in which a single suture is placed in the left anterior descending artery to occlude blood flow to the apex of the heart. The hydrogel patch can then be placed at the site of infarction to deliver stem cells and beneficial factors to the heart surface. Initial tests showed that hydrostatic forces were enough to hold the patch in place on a beating heart, but could not sustain adhesion after closure of the chest cavity. To compensate for this lack of adhesion, the patch thickness was decreased to allow for better conformation with the heart and a mix of iron chloride and HA-DA was used as an additional layer that aids in patch adhesion. The thinner patch with adhesive layer proved to adhere to the heart and remain in place following chest cavity closure. These promising results provide the foundation to test the efficacy of the patch in aiding in tissue healing or preventing tissue degradation in a mouse myocardial infarction model using a combination of echocardiogram measurements and histology testing.