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

• Research Article

TISSUE ENGINEERING

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

1. Sonya B. Seif-Naraghi¹,*,
2. Jennifer M. Singelyn¹,*,
3. Michael A. Salvatore²,
4. Kent G. Osborn¹,
5. Jean J. Wang¹,
6. Unatti Sampat¹,
7. Oi Ling Kwan¹,
8. G. Monet Strachan¹,
9. Jonathan Wong³,
10. Pamela J. Schup-Magoffin¹,
11. Rebecca L. Braden¹,
12. Kendra Bartels¹,
13. Jessica A. DeQuach²,
14. Mark Preul⁴,
15. Adam M. Kinsey²,
16. Anthony N. DeMaria¹,
17. Nabil Dib¹ and
18. Karen L. Christman¹,†

+ Author Affiliations

1. ¹University of California, San Diego, La Jolla, CA 92093, USA.
2. ²Ventrix, Inc., San Diego, CA 92109, USA.
3. ³Biologics Delivery Systems, Irwindale, CA 91706, USA.
4. ⁴Barrow Neurological Institute, Phoenix, AZ 85013, USA.

+ Author Notes

• ↵* These authors contributed equally to this work.

1. ↵†To whom correspondence should be addressed. E-mail: christman@eng.ucsd.edu

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.

• Copyright © 2013, American Association for the Advancement of Science

Citation: S. B. Seif-Naraghi, J. M. Singelyn, M. A. Salvatore, K. G. Osborn, J. J. Wang, U. Sampat, O. L. Kwan, G. M. Strachan, J. Wong, P. J. Schup-Magoffin, R. L. Braden, K. Bartels, J. A. DeQuach, M. Preul, A. M. Kinsey, A. N. DeMaria, N. Dib, K. L. Christman, Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial Infarction. Sci. Transl. Med. 5, 173ra25 (2013).

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