Intramyocardial injection of a fully synthetic hydrogel attenuates left ventricular remodeling post myocardial infarction

Abstract

Intramyocardial hydrogel injection is an innovative and promising treatment for myocardial infarction (MI) and has recently entered clinical trials. By providing mechanical support to the ventricular wall, hydrogel injectate may act to preserve cardiac function and slow the remodeling process that leads to heart failure. However, improved outcomes will likely depend on the use of hydrogels specifically designed for this unique application, and better understanding of the mechanisms affected by the intervention. In this work, we present the first large animal study achieving functional and geometrical improvements in treating MI using a relatively stiff, fully synthetic hydrogel designed for intramyocardial injection. In addition, the renin-angiotensin system coincided with the mechanical effects of hydrogel injection and attenuated left ventricular remodeling, even after significant hydrogel degradation had occurred in vivo. These results may inspire further optimization of hydrogel materials used in intramyocardial hydrogel injection therapy and a better description of physiologic pathways affected by its implementation to facilitate successful clinical translation.

Keywords: Biomaterials; Biomechanics; Hydrogel; Lab-on-a-chip; Myocardial infarction; iPSCs.