Delivery of an engineered HGF fragment in an extracellular matrix-derived hydrogel prevents negative LV remodeling post-myocardial infarction.

Sonya B Sonnenberg, Aboli A Rane, Cassie J Liu, Nikhil Rao, Gillie Agmon, Sophia Suarez, Raymond Wang, Adam Munoz, Vaibhav Bajaj, Shirley Zhang, Rebecca Braden, Pamela J Schup-Magoffin, Oi Ling Kwan, Anthony N DeMaria, Jennifer R Cochran, Karen L Christman

Index: Biomaterials 45 , 56-63, (2015)

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Abstract

Hepatocyte growth factor (HGF) has been shown to have anti-fibrotic, pro-angiogenic, and cardioprotective effects; however, it is highly unstable and expensive to manufacture, hindering its clinical translation. Recently, a HGF fragment (HGF-f), an alternative c-MET agonist, was engineered to possess increased stability and recombinant expression yields. In this study, we assessed the potential of HGF-f, delivered in an extracellular matrix (ECM)-derived hydrogel, as a potential treatment for myocardial infarction (MI). HGF-f protected cardiomyocytes from serum-starvation and induced down-regulation of fibrotic markers in whole cardiac cell isolate compared to the untreated control. The ECM hydrogel prolonged release of HGF-f compared to collagen gels, and in vivo delivery of HGF-f from ECM hydrogels mitigated negative left ventricular (LV) remodeling, improved fractional area change (FAC), and increased arteriole density in a rat myocardial infarction model. These results indicate that HGF-f may be a viable alternative to using recombinant HGF, and that an ECM hydrogel can be employed to increase growth factor retention and efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.