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


CONCLUSIONS
Biomaterials for treating myocardial infarction have become an increasingly popular area of research. Within the past few years, this work has transitioned to some large animals models, and Phase I & II clinical trials. While these materials have preserved/improved cardiac function the effect of these materials on arrhythmogenesis, which is of considerable concern when injecting anything into the heart, has yet to be understood. Our manuscript is therefore a first of its kind in that it directly examines the potential of an injectable material to create a substrate for arrhythmias. This work suggests that site of delivery and distribution in the tissue are important criteria in the design and development of future biomaterial therapies for myocardial infarction treatment.
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093, USA.
Sophia L
SL
Suarez
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Aboli A
AA
Rane
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Adam
A
Muñoz
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Adam T
AT
Wright
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Shirley X
SX
Zhang
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Rebecca L
RL
Braden
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: aalmutairi@ucsd.edu.
Adah
A
Almutairi
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Andrew D
AD
McCulloch
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: christman@bioeng.ucsd.edu.
Karen L
KL
Christman
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000494:pharmacology; D004553:Electric Conductivity; D005260:Female; D006329:Heart Conduction System / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000737:chemistry / Q000187:drug effects; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry*; D007267:Injections; D009431:Neural Conduction / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001672:Biocompatible Materials; D020100:Hydrogels
Biomaterial; Electrophysiology; Myocardial infarction; Optical mapping