Cardiovascular disease can lead to myocardial infarction (Ml) and subsequent heart failure. There are currently a number of therapies aimed at preventing or treating heart failure post-MI. Only heart transplantation replaces infarcted myocardium to restore heart function, but there is a paucity of donor hearts and the incidence of cardiovascular disease continues to rise. A new and innovative option is the use of "heart patches" created in vitro for implantation in vivo. The research proposed in the independent phase of this award aims to address 2 critical issues pertaining to the function and eventual use of such heart patches: 1) the effect of a biomimetic culture environment on tissue morphology and function, and 2) the efficacy of myocardial equivalents biomimetically-engineered in vitro in restoring left ventricular function post-MI. The overall hypothesis of this work is that myocardium engineered in vitro in biomimetic culture conditions restores post-MI left ventricular function better than cell therapy-based methods of repair. The environment at the Tufts University uniquely positions me to address this hypothesis, as the world-renowned Tissue Engineering Research Center and Molecular Cardiology Research Institute are both located nearby. This environment will give me the opportunity to augment my already considerable background in tissue mechanics and tissue engineering methods with cardiac anatomy and physiology in health and disease and cardiac surgical techniques. The continuation of my career plan during the independent phase includes gaining more expertise in cell and tissue culture techniques and bioreactor development, while learning new skills in areas including cardiac surgical techniques and physiological evaluation in a rat model of Ml. The ultimate goal of the project is to leverage these skills to directly compare the efficacy of myocardial tissue engineered in vitro with current cell-therapy based methods of cardiac repair in restoring function to the left ventricle post-MI. This research is especially critical considering the continuing rise in incidence of heart disease. The results of this research may help elucidate design parameters that are critical to the creation of functional myocardium engineered in vitro and thus advance the concept of the "heart patch" closer to reality

Public Health Relevance

This research proposal regards the study of a high potential method for repair of the heart during heart failure, which is especially critical considering the increase in incidence of heart disease. The proposed research aims to elucidate critical design parameters in the creation and culture of heart tissue engineered in the lab and to find way to improve this tissue's efficacy in restoring functionality to the injured heart.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Transition Award (R00)
Project #
5R00HL093358-04
Application #
8270013
Study Section
Special Emphasis Panel (NSS)
Program Officer
Lee, Albert
Project Start
2010-05-24
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
4
Fiscal Year
2012
Total Cost
$249,000
Indirect Cost
$70,581
Name
Tufts University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
073134835
City
Medford
State
MA
Country
United States
Zip Code
02155
Quinn, Kyle P; Sullivan, Kelly E; Liu, Zhiyi et al. (2016) Optical metrics of the extracellular matrix predict compositional and mechanical changes after myocardial infarction. Sci Rep 6:35823
Stoppel, Whitney L; Kaplan, David L; Black 3rd, Lauren D (2016) Electrical and mechanical stimulation of cardiac cells and tissue constructs. Adv Drug Deliv Rev 96:135-55
Williams, Corin; Budina, Erica; Stoppel, Whitney L et al. (2015) Cardiac extracellular matrix-fibrin hybrid scaffolds with tunable properties for cardiovascular tissue engineering. Acta Biomater 14:84-95
Williams, Corin; Sullivan, Kelly; Black 3rd, Lauren D (2015) Partially Digested Adult Cardiac Extracellular Matrix Promotes Cardiomyocyte Proliferation In Vitro. Adv Healthc Mater 4:1545-54
Sullivan, Kelly E; Burns, Laura J; Black 3rd, Lauren D (2015) An in vitro model for the assessment of stem cell fate following implantation within the infarct microenvironment identifies ISL-1 expression as the strongest predictor of c-Kit(+) cardiac progenitor cells' therapeutic potential. J Mol Cell Cardiol 88:91-100
Sullivan, Kelly Elizabeth; Quinn, Kyle Patrick; Tang, Katherine Michele et al. (2014) Extracellular matrix remodeling following myocardial infarction influences the therapeutic potential of mesenchymal stem cells. Stem Cell Res Ther 5:14
Morgan, Kathy Ye; Black 3rd, Lauren Deems (2014) It's all in the timing: modeling isovolumic contraction through development and disease with a dynamic dual electromechanical bioreactor system. Organogenesis 10:317-22
Williams, C; Quinn, K P; Georgakoudi, I et al. (2014) Young developmental age cardiac extracellular matrix promotes the expansion of neonatal cardiomyocytes in vitro. Acta Biomater 10:194-204
Lan, Jen-Yu; Williams, Corin; Levin, Michael et al. (2014) Depolarization of Cellular Resting Membrane Potential Promotes Neonatal Cardiomyocyte Proliferation In Vitro. Cell Mol Bioeng 7:432-445
Lau, Jason J; Wang, Raymond M; Black 3rd, Lauren D (2014) Development of an arbitrary waveform membrane stretcher for dynamic cell culture. Ann Biomed Eng 42:1062-73

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