A Bioengineered Neuregulin-Hydrogel Therapy Reduces Scar Size and Enhances Post-Infarct Ventricular Contractility in an Ovine Large Animal Model

Journal of Cardiovascular Development and Disease
Jeffrey E CohenY Joseph Woo

Abstract

The clinical efficacy of neuregulin (NRG) in the treatment of heart failure is hindered by off-target exposure due to systemic delivery. We previously encapsulated neuregulin in a hydrogel (HG) for targeted and sustained myocardial delivery, demonstrating significant induction of cardiomyocyte proliferation and preservation of post-infarct cardiac function in a murine myocardial infarction (MI) model. Here, we performed a focused evaluation of our hydrogel-encapsulated neuregulin (NRG-HG) therapy's potential to enhance cardiac function in an ovine large animal MI model. Adult male Dorset sheep (n = 21) underwent surgical induction of MI by coronary artery ligation. The sheep were randomized to receive an intramyocardial injection of saline, HG only, NRG only, or NRG-HG circumferentially around the infarct borderzone. Eight weeks after MI, closed-chest intracardiac pressure-volume hemodynamics were assessed, followed by heart explant for infarct size analysis. Compared to each of the control groups, NRG-HG significantly augmented left ventricular ejection fraction (p = 0.006) and contractility based on the slope of the end-systolic pressure-volume relationship (p = 0.006). NRG-HG also significantly reduced infarct scar size (p =...Continue Reading

References

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Citations

May 29, 2021·Frontiers in Cell and Developmental Biology·Stefan EldeY Joseph Woo
Jun 19, 2021·Frontiers in Bioengineering and Biotechnology·Stefan EldeY Joseph Woo

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Methods Mentioned

BETA
nuclear magnetic resonance
rheometry

Clinical Trials Mentioned

NCT03388593
NCT01214096

Software Mentioned

ImageJ

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