title: Safety and efficacy of an injectable extracellular matrix hydrogel for treating myocardial infarction.
abstract: 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.
authors: University of California, San Diego, La Jolla, CA 92093, USA.
authors: Sonya B
authors: SB
authors: Seif-Naraghi
authors: Jennifer M
authors: JM
authors: Singelyn
authors: Michael A
authors: MA
authors: Salvatore
authors: Kent G
authors: KG
authors: Osborn
authors: Jean J
authors: JJ
authors: Wang
authors: Unatti
authors: U
authors: Sampat
authors: Oi Ling
authors: OL
authors: Kwan
authors: G Monet
authors: GM
authors: Strachan
authors: Jonathan
authors: J
authors: Wong
authors: Pamela J
authors: PJ
authors: Schup-Magoffin
authors: Rebecca L
authors: RL
authors: Braden
authors: Kendra
authors: K
authors: Bartels
authors: Jessica A
authors: JA
authors: DeQuach
authors: Mark
authors: M
authors: Preul
authors: Adam M
authors: AM
authors: Kinsey
authors: Anthony N
authors: AN
authors: DeMaria
authors: Nabil
authors: N
authors: Dib
authors: Karen L
authors: KL
authors: Christman
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D005109:Extracellular Matrix; D020100:Hydrogels / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000628:therapy*; D013552:Swine
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels