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

作者：Sonnenberg Sonya B; Rane Aboli A; Liu Cassie J; Rao Nikhil; Agmon Gillie; Suarez Sophia; Wang Raymond; Munoz Adam; Bajaj Vaibhav; Zhang Shirley; Braden Rebecca; Schup Magoffin Pamela J; Kwan Oi Ling; De Maria Anthony N; Cochran Jennifer R; Christman Karen L^*

来源：Biomaterials, 2015, 45: 56-63.

DOI：10.1016/j.biomaterials.2014.12.021

• Myocardial infarction
• Growth factor
• Extracellular matrix
• Decellularization
• Hydrogel

Hepatocyte growth factor (HGF) has been shown to have anti-fibrotic, pro-angiogenic, and cardio-protective 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.

• 出版日期2015-3