RT Journal Article
SR Electronic
T1 Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial Infarction
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 173ra25
OP 173ra25
DO 10.1126/scitranslmed.3005503
VO 5
IS 173
A1 Seif-Naraghi, Sonya B.
A1 Singelyn, Jennifer M.
A1 Salvatore, Michael A.
A1 Osborn, Kent G.
A1 Wang, Jean J.
A1 Sampat, Unatti
A1 Kwan, Oi Ling
A1 Strachan, G. Monet
A1 Wong, Jonathan
A1 Schup-Magoffin, Pamela J.
A1 Braden, Rebecca L.
A1 Bartels, Kendra
A1 DeQuach, Jessica A.
A1 Preul, Mark
A1 Kinsey, Adam M.
A1 DeMaria, Anthony N.
A1 Dib, Nabil
A1 Christman, Karen L.
YR 2013
UL http://stm.sciencemag.org/content/5/173/173ra25.abstract
AB 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.