NIPAAm-co-PEG4000 thermoresponsive hydrogel with ROS scavenging properties improves in vivo border zone contractility and reduces myocardial remodeling in sheep after MI.

Abstract

Decreased contractility of the border zone (BZ) myocardium after MI is associated with oxidative stress mediated contractile protein dysfunction. We hypothesized that injection of a thermo-responsive hydrogel with enhanced reactive oxygen species (ROS) scavenging would improve the in vivo contractility of BZ myocardium. To that end, 14 adult male sheep underwent MI. Of those, 6 sheep had a comb-like copolymer synthesized from N-isopropyl acrylamide and 4000 MW methoxy poly(ethylene glycol) methacrylate (NIPAAm-co-PEG4000) injected into the MI zone (MI+Hydrogel). In vivo cardiac magnetic resonance imaging (CMR), including cine DENSE (Displacement encoding with stimulated echoes), was performed before and 6 weeks after MI to measure LV geometry and regional displacement. Tissue ROS and in vitro muscle strip developed force were measured in the BZ and remote regions. Compared to the MI group 6 weeks after MI, MI+Hydrogel exhibited: 1) a reduction in indexed LV end-diastolic (ED) volume; 2) an increase in average wall thickness at ED; and, 3) an increase in average peak circumferential strain in the BZ near the MI border. ROS was significantly lower in the MI+Hydrogel group and muscle strip developed force was significantly increased in the BZ. These observations support the hypothesis that injection of a hydrogel with enhanced ROS scavenging improves in vivo BZ contractility and attenuates ventricular remodeling after MI in sheep. STATEMENT OF SIGNIFICANCE: This work supports our hypothesis that intramyocardial injection of hydrogel with enhanced reactive oxygen species (ROS) scavenging improves in vivo contractility of myocardium bordering the infarct and attenuates pathological ventricular remodeling after myocardial infarction. We believe this multidisciplinary research would be of interest by researchers in the fields of hydrogel biomaterials, finite element biomechanical analysis, and cardiovascular diseases.