Myocardial matrix hydrogel acts as a reactive oxygen species scavenger and supports a proliferative microenvironment for cardiomyocytes

As the native regenerative potential of adult cardiac tissue is limited post-injury, stimulating endoge-nous repair mechanisms in the mammalian myocardium is a potential goal of regenerative medicine therapeutics. Injection of myocardial matrix hydrogels into the heart post-myocardial infarction (MI) has demonstrated increased cardiac muscle and promotion of pathways associated with cardiac development, suggesting potential promotion of cardiomyocyte turnover. In this study, the myocardial matrix hydrogel was shown to have native capability as an effective reactive oxygen species scavenger and protect against oxidative stress induced cell cycle inhibition in vitro . Encapsulation of cardiomyocytes demonstrated an enhanced turnover in in vitro studies, and in vivo assessments of myocardial matrix hydrogel treatment post-MI showed increased thymidine analog uptake in cardiomyocyte nuclei compared to saline con-trols. Overall, this study provides evidence that properties of the myocardial matrix material provide a microenvironment mitigating oxidative damage and supportive of cardiomyocytes undergoing DNA syn-thesis, toward possible DNA repair or cell cycle activation.Statement of significance Loss of adult mammalian cardiomyocyte turnover is influenced by shifts in oxidative damage, which rep-resents a potential mechanism for improving restoration of cardiac muscle after myocardial infarction (MI). Injection of a myocardial matrix hydrogel into the heart post-MI previously demonstrated increased cardiac muscle and promotion of pathways associated with cardiac development, suggesting potential in promoting proliferation of cardiomyocytes. In this study, the myocardial matrix hydrogel was shown to protect cells from oxidative stress and increase proliferation in vitro. In a rat MI model, greater presence of tissue free thiol content spared from oxidative damage, lesser mitochondrial superoxide content, and increased thymidine analog uptake in cardiomyocytes was found in matrix injected animals compared to saline controls. Overall, this study provides evidence that properties of the myocardial matrix material provide a microenvironment supportive of cardiomyocytes undergoing DNA synthesis, toward possible DNA repair or cell cycle activation.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study demonstrates that myocardial matrix hydrogel exhibits the ability to scavenge reactive oxygen species and protect cells from oxidative stress, as well as enhance cell proliferation. In in vivo experiments using a rat myocardial infarction model, animals treated with matrix injection showed increased thymidine analog uptake in cardiomyocytes, reduced oxidative damage, and improved preservation of tissue free thiol content compared to saline controls. Overall, this study provides evidence that the properties of the myocardial matrix material create a supportive microenvironment for cardiomyocytes undergoing DNA synthesis, potentially facilitating DNA repair or cell cycle activation.