Biomaterial delivery of exogenous Mir-29b to the infarcted myocardium yields improved myocardial recovery

Heart failure due to adverse remodelling remains a common complication following myocardial infarction (MI) and there exists excessive and dehabilitating fibrosis at the peri-infarct region due to cardiac fibroblast deposition of collagen types I and III. Expression of miR-29b is higher in cardiac fibroblasts than in cardiomyocytes, but is downregulated in the border zone of infarcted hearts1. It is therefore feasible to assume that delivery of exogenous miR-29b could inhibit production of collagen types I and III, resulting in less fibrosis. It is the hypothesis of this study that exogenous miR-29b can inhibit dehabilitating fibrosis following MI. We aimed to deliver miR-29b via localized biomaterial intramyocardial delivery to ensure a clinically relevant delivery, and also to eradicate possible off target effects in other organs. Transient ischemia was induced in C57BL/6J mice via left ascending coronary artery occlusion. Following reperfusion, miR-29b (100 mg/animal) was delivered within a hyaluronan-based hydrogel (crosslinked using thiol-reactive poly(ethylene glycol) diacrylate) via intramyocardial injection at five infarct borderzone locations. miR-239b was employed as a negative control. At 14 and 35 days following MI, miR-29b-treated mice showed significantly improved ejection fractions and fractional shortening when assessed using echocardiography. Histological and immunohistological analyses also revealed differences in extracellular matrix patterns. miR-29B could be considered as a possible therapeutic intervention when delivered locally to the infarcted myocardium due to its influence on the remodelling myocardium.