Injectable extracellular matrix hydrogels for cardiac repair

Cardiovascular disease is the leading cause of death in the United States and the rest of the western world. Interrupting the progression of negative remodeling after a myocardial infarction (MI) could mitigate the damage caused by a heart attack and preventing the onset of heart failure. Extracellular matrix (ECM) hydrogels have emerged as potential scaffolds for cardiac repair; however, all ECM hydrogels previously explored have been derived from xenogeneic sources, raising concerns regarding immunogenicity, disease transfer, and increased regulation by the FDA. In this dissertation work, a potentially autologous pericardial matrix hydrogel is developed, characterized, and tested. The presence of sulfated sugars in the material led to the hypothesis that heparin-binding growth factors could be sequestered for prolonged delivery and increased effect in vivo. The positive results of this work prompted the exploration of delivering a novel growth factor candidate with the pericardial matrix to evaluate the potential effect on cardiac function post-MI, demonstrating the potential value of this growth factor delivery system in vivo. Though concerns regarding using a xenogeniec material provided the basis for first investigating an autologous option, understanding the effect on the host response is important, prompting evaluation of the inflammatory response to rat myocardial matrix compared to porcine myocardial matrix. Using a non- decellularized myocardial matrix and saline as controls, we sought to understand the inflammatory response to allogeneic and xenogeneic materials in healthy animals. The only signs of chronic inflammation were seen in the non-decellularized positive controls; little difference was noted between the porcine and rat ECM hydrogels, supporting the conclusion that there may be no added value to allogeneic over xenogeneic materials. Exposure to myocardial matrix had no effect on clotting times or platelet activation in human blood and platelet-rich- plasma samples. Direct injection of the ECM ...