Myocardial tissue lacks the ability to significantly regenerate itself following a myocardial infarction, thus tissue engineering strategies are required for repair. Several injectable materials have been examined for cardiac tissue engineering; however, none have been designed specifically to mimic the myocardium. The goal of this study was to investigate the in vitro properties and in vivo potential of an injectable myocardial matrix designed to mimic the natural myocardial extracellular environment. Porcine myocardial tissue was decellularized and processed to form a myocardial matrix with the ability to gel in vitro at 37°C and in vivo upon injection into rat myocardium. The resulting myocardial matrix maintained a complex composition, including glycosaminoglycan content, and was able to self-assemble to form a nanofibrous structure. Endothelial cells and smooth muscle cells were shown to migrate towards the myocardial matrix both in vitro and in vivo, with a significant increase in arteriole formation at 11 days post-injection. The matrix was also successfully pushed through a clinically used catheter, demonstrating its potential for minimally invasive therapy. Thus, we have demonstrated the initial feasibility and potential of a naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering.

New therapies are needed to prevent heart failure after myocardial infarction (MI). As experimental treatment strategies for MI approach translation, safety and efficacy must be established in relevant animal models that mimic the clinical situation. We have developed an injectable hydrogel derived from porcine myocardial extracellular matrix (ECM) as a scaffold for cardiac repair post-MI. In this study, we establish the safety and efficacy of this injectable biomaterial in large-and small-animal studies that simulate the clinical setting. Infarcted pigs were treated with percutaneous transendocardial injections of the myocardial matrix hydrogel two weeks post-MI and evaluated after three months. Echocardiography indicated improvement in cardiac function, ventricular volumes, and global wall motion scores. Furthermore, a significantly larger zone of cardiac muscle was found at the endocardium in matrix-injected pigs compared to controls. In rats, we establish the safety of this biomaterial and explore the host response via direct injection into the left ventricular lumen and in an inflammation study, both of which support the biocompatibility of this material. Hemocompatibility studies with human blood indicate that exposure to the material at relevant concentrations does not affect clotting times or platelet activation. This work therefore provides a strong platform to move forward in clinical studies with this cardiac-specific biomaterial that can be delivered by catheter.

Objectives This study evaluated the use of an injectable hydrogel derived from ventricular extracellular matrix (ECM) for treating myocardial infarction (MI) and its ability to be delivered percutaneously. Background Injectable materials offer promising alternatives to treat MI. While most of the examined materials have shown preserved or improved cardiac function in small animal models, none have been specifically designed for the heart and few have translated to catheter delivery in large animal models. Methods We have developed a myocardial specific hydrogel, derived from decellularized ventricular ECM, which self-assembles when injected in vivo. Female Sprague-Dawley rats underwent ischemia reperfusion followed by injection of the hydrogel or saline 2 weeks later. The implantation response was assessed via histology and immunohistochemistry, and potential for arrhythmogenesis was examined using programmed electrical stimulation 1 week post-injection. Cardiac function was analyzed with magnetic resonance imaging 1 week pre-injection and 4 weeks post-MI. In a porcine model, we delivered the hydrogel using the NOGA guided Myostar catheter, and utilized histology to assess retention of the material. Results We demonstrate that injection of the material in the rat MI model increases endogenous cardiomyocytes in the infarct area and maintains cardiac function without inducing arrhythmias. Furthermore, we demonstrate feasibility of transendocardial catheter injection in a porcine model. Conclusion To our knowledge, this is the first in situ gelling material to be delivered via transendocardial injection in a large animal model, a critical step towards the translation of injectable materials for treating myocardial infarction in humans. Our results warrant further study of this material in a large animal model of myocardial infarction and suggest this may be a promising new therapy for treating myocardial infarction.

Cardiovascular disease continues to be the leading cause of death, suggesting that new therapies are needed to treat the progression of heart failure post-myocardial infarction. As cardiac tissue has a limited ability to regenerate itself, experimental biomaterial therapies have focused on the replacement of necrotic cardiomyocytes and repair of the damaged extracellular matrix. While acellular and cellular cardiac patches are applied surgically to the epicardial surface of the heart, injectable materials offer the prospective advantage of minimally invasive delivery directly into the myocardium to either replace the damaged extracellular matrix or to act as a scaffold for cell delivery. Cardiac-specific decellularized matrices offer the further advantage of being biomimetic of the native biochemical and structural matrix composition, as well as the potential to be autologous therapies. This review will focus on the requirements of an ideal scaffold for catheter-based delivery as well as highlight the promise of decellularized matrices as injectable materials for cardiac repair.