title: Catheter-deliverable hydrogel derived from decellularized ventricular extracellular matrix increases endogenous cardiomyocytes and preserves cardiac function post-myocardial infarction.
abstract: OBJECTIVE
  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. Although 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 the 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 (Biologics Delivery Systems, Irwindale, California), 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.
  
  
  CONCLUSIONS
  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 MI in humans. Our results warrant further study of this material in a large animal model of MI and suggest this may be a promising new therapy for treating MI.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Singelyn
authors.forename: Priya
authors.initials: P
authors.lastname: Sundaramurthy
authors.forename: Todd D
authors.initials: TD
authors.lastname: Johnson
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Schup-Magoffin
authors.forename: Diane P
authors.initials: DP
authors.lastname: Hu
authors.forename: Denver M
authors.initials: DM
authors.lastname: Faulk
authors.forename: Jean
authors.initials: J
authors.lastname: Wang
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Mayle
authors.forename: Kendra
authors.initials: K
authors.lastname: Bartels
authors.forename: Michael
authors.initials: M
authors.lastname: Salvatore
authors.forename: Adam M
authors.initials: AM
authors.lastname: Kinsey
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Demaria
authors.forename: Nabil
authors.initials: N
authors.lastname: Dib
authors.forename: Karen L
authors.initials: KL
authors.lastname: Christman
mesh_terms: D000818:Animals; D002404:Catheterization / Q000379:methods*; D002452:Cell Count; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000378:metabolism; D007150:Immunohistochemistry; D007267:Injections; D019028:Magnetic Resonance Imaging, Cine; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013552:Swine; D016276:Ventricular Function / Q000187:drug effects*
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate