Author + information
- Received August 25, 2011
- Revision received October 27, 2011
- Accepted October 28, 2011
- Published online February 21, 2012.
- Jennifer M. Singelyn, PhD⁎,
- Priya Sundaramurthy, MS⁎,
- Todd D. Johnson, BS⁎,
- Pamela J. Schup-Magoffin, BA⁎,
- Diane P. Hu, MS⁎,
- Denver M. Faulk, BS⁎,
- Jean Wang, BS⁎,
- Kristine M. Mayle, BS⁎,
- Kendra Bartels, RN†,
- Michael Salvatore, BS‡,
- Adam M. Kinsey, PhD‡,
- Anthony N. DeMaria, MD†,
- Nabil Dib, MD, MSc† and
- Karen L. Christman, PhD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Karen L. Christman, University of California, 9500 Gilman Drive, MC 0412, La Jolla, California 92093
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. 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.
This research was supported in part by the National Institutes of Health (NIH) Director's New Innovator Award Program, part of the NIH Roadmap for Medical Research, through grant number 1-DP2-OD004309, the Wallace H. Coulter Foundation (Miami, Florida), and National Science Foundation grant NSF 1014429. Mr. Salvatore and Dr. Kinsey are employees of Ventrix, Inc. Dr. DeMaria is on the scientific advisory board of Ventrix, Inc. Dr. Dib is a consultant for Biologics Delivery System. Drs. Dib and Christman hold equity interest in Ventrix, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Joshua M. Hare, MD, FACC, FAHA, served as Guest Editor of this paper.
- Received August 25, 2011.
- Revision received October 27, 2011.
- Accepted October 28, 2011.
- American College of Cardiology Foundation