Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial Infarction

A hydrogel derived from myocardial extracellular matrix mitigates negative left ventricular remodeling and improves heart function after myocardial infarction in pigs. Healing Biomaterial Delivered to Heart Repairing a broken heart takes more than just time—it may also take a special hydrogel material derived from the heart itself. After a heart attack, cells die and are replaced by a thick scar, which cannot pump blood like normal tissue. This results in total heart failure and death in these patients that survive the initial heart attack. In response, Seif-Naraghi and colleagues have developed a biomaterial that can be injected into the heart to prevent scar formation and help the heart to heal and function as it normally would. The authors used a pig model to study the effects of a myocardial extracellular matrix (ECM)–derived biomaterial on heart healing after myocardial infarction (MI). Two weeks after MI, the material was delivered via catheter to the target region of the heart—much like it would in a real clinical trial with patients. Control animals received either no injection or saline only. After 3 months, tests were performed to see if the heart had healed, if it functioned properly, and if the material caused any irritation to the heart tissue. Seif-Naraghi et al. reported improvements in heart function in the matrix-injected animals and worsening of function in the controls. Their data suggest that the matrix can prevent post-MI negative left ventricular remodeling by improving systolic function and contractility. Other than function, the material appeared to encourage healthy muscle and blood vessel formation in the infarcted areas, whereas tissue from control animals was thin and fibrotic. This myocardial matrix material did not damage peripheral tissues, such as the lungs and liver, or disrupt cardiac rhythm in pigs. Even with direct injection into the left ventricle lumen in rats, there was no inflammation, edema, or hemorrhage. These data in a large animal show that the myocardial ECM–derived material not only improves functional outcome after a heart attack but also is safe and nontoxic, thus making the material ready to move forward toward clinical tests in people. 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 as a scaffold for cardiac repair after MI. 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 2 weeks after MI and evaluated after 3 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.