Intramyocardial injection of hydrogel with high interstitial spread does not impact action potential propagation

Abstract

Injectable biomaterials have been evaluated as potential new therapies for myocardial infarction (MI) and heart failure. These materials have improved left ventricular (LV) geometry and ejection fraction, yet there remain concerns that biomaterial injection may create a substrate for arrhythmia. Since studies of this risk are lacking, we utilized optical mapping to assess the effects of biomaterial injection and interstitial spread on cardiac electrophysiology. Healthy and infarcted rat hearts were injected with a model poly(ethylene glycol) hydrogel with varying degrees of interstitial spread. Activation maps demonstrated delayed propagation of action potentials across the LV epicardium in the hydrogel-injected group when compared to saline and no-injection groups. However, the degree of the electrophysiological changes depended on the spread characteristics of the hydrogel, such that hearts injected with highly spread hydrogels showed no conduction abnormalities. Conversely, the results of this study indicate that injection of a hydrogel exhibiting minimal interstitial spread may create a substrate for arrhythmia shortly after injection by causing LV activation delays and reducing gap junction density at the site of injection. Thus, this work establishes site of delivery and interstitial spread characteristics as important factors in the future design and use of biomaterial therapies for MI treatment.

A comparison of two quasi‐static computational models for assessment of intra‐myocardial injection as a therapeutic strategy for heart failure

“…Both the direct infarct injection [8][9][10] and BZ injection [39][40][41] have shown functional benefits experimentally. To our knowledge, an experimental comparison of these two injection strategies has not been reported.…”

Thermosensitive, fast gelling, photoluminescent, highly flexible, and degradable hydrogels for stem cell delivery

“…The cell density in the hydrogel group was ~6.0 times and ~16.9 times of collagen and PBS groups, respectively. One of the concerns in using fast gelling hydrogels is that the formed bolus may disrupt electrical conductivity in the heart tissue [87]. However, the hydrogels will be injected into the infarcted region where electrical conductivity is very low.…”

Ventricular wall biomaterial injection therapy after myocardial infarction: Advances in material design, mechanistic insight and early clinical experiences

“…Principal component analysis and pathway analysis showed that alterations in pathways associated with the inflammatory response (Figure 4), cardiomyocyte apoptosis, infarct neovascularization, cardiac hypertrophy and fibrosis, metabolic enzyme expression, cardiac transcription factor expression, and progenitor cell recruitment all may have contributed to cardiac functional improvement [68]. Suarez et al explored the influence of biomaterial injection on action potential propagation across the heart [69]. PEG hydrogels were injected into healthy and infarcted rat hearts as a model material and were found to delay action potential propagation across the LV epicardium compared to saline injection and sham controls [69].…”

“…Suarez et al explored the influence of biomaterial injection on action potential propagation across the heart [69]. PEG hydrogels were injected into healthy and infarcted rat hearts as a model material and were found to delay action potential propagation across the LV epicardium compared to saline injection and sham controls [69]. In addition, it was found that a highly diffused hydrogel does not alter action potential propagation, while a hydrogel that did not spread as extensively would reduce gap junction densities and may create a substrate for arrhythmias [69].…”

“…As noted previously, an injected hydrogel with minimal interstitial spreading may delay LV activation upon injection and reduce gap junction density, possibly resulting in an arrhythmia [69]. Therefore, efforts have been made to fabricate conductive injectable biomaterials for MI treatment.…”