Heart disease is the leading cause of death and morbidity in many countries in the developed world, including the United States. Due to the terminally differentiated and non-proliferative nature of cardiomyocytes, the heart is unable to regenerate and repair itself after infarction, and the resulting chronic cardiac dysfunction often leads to death within 5 years. Stem cell-based therapies involving the direct injection of cells into infarcted tissue have garnered much attention recently. However, while these therapies hold tremendous potential, the overwhelming cell death and limited ability of graft cells to integrate with the surrounding host tissue limit their effectiveness at restoring cardiac function. The goal of the proposed research is to develop injectable, three- dimensional myocardial matrix-graphene composite scaffolds that mimic the electrical, mechanical and biochemical environmental cues seen in healthy myocardium, and then to test their ability to generate functional tissues. The central hypothesis is that the high conductivity of graphene will enhance action potential propagation through direct and indirect (e.g. increased gap junction formation) mechanisms, thereby improving the functionality of the incorporated human induced pluripotent stem cell-derived cardiomyocytes. By combining the unique characteristics of graphene and native myocardial matrices synergistically, we aim to create a new class of three-dimensional scaffolds for the engineering of cardiac tissues for therapeutic purposes. Towards this end, we will first develop biocompatible and injectable myocardial matrix-graphene 3D composite scaffolds with tunable electrical and mechanical properties. Then we will evaluate the capability of conductive 3D composite scaffolds in enhancing cardiomyocyte electrophysiological function in vitro.

Public Health Relevance

Heart disease leading to the development of myocardial infarctions is the leading cause of death and morbidity in the United States. This application seeks to investigate the synergistic effects of electrical and biochemical cues on cardiomyocyte function, and to use this knowledge to develop an innovative class of injectable three- dimensional scaffolds for the engineering of cardiac tissues. The biocompatibility and electrical and biochemical properties of our developed scaffolds will be examined, and the ability of these electroconductive scaffolds to enhance the electrophysiological function of cultured cardiomyocytes will be assessed by tracking electrical signal propagation in response to cell stimulation in vitro.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB020132-01A1
Application #
9034827
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Hunziker, Rosemarie
Project Start
2016-09-30
Project End
2018-07-31
Budget Start
2016-09-30
Budget End
2017-07-31
Support Year
1
Fiscal Year
2016
Total Cost
$227,486
Indirect Cost
$77,486
Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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