Cardiovascular disease affects 80 million people in the US and is the leading cause of death. Significant limitations of current treatments necessitate the development of novel strategies. Cardiovascular tissue engineering is an emerging field focused on the development of biological substitutes to restore, maintain, or improve tissue function. Bioengineered 3-dimensional (3D) cardiac patches can be utilized clinically at the site of a myocardial infarction, promoting increased left ventricular contractile function. This study is focused on the fabrication of 3D heart muscle, using controlled stretch to support tissue development and testing the ability of cardiac patches to augment the function of infarcted myocardium. The proposed study is divided into three components. The first part of this study is focused on defining cell culture conditions to maximize the functional performance of 3D cardiac patches. The second part is focused on developing protocols to deliver controlled stretch to the 3D cardiac patches, in order to further increase the functional performance of cardiac patches. In the third part of this project, cardiac patches fabricated using optimized cell culture conditions and conditioned using stretch, will be implanted on the surface of infarcted hearts. The ability of the cardiac patches to augment the functional performance of failing myocardium will be studied, as a function of post-injury time and patch implantation time. Successful completion of this study will result in the development of 3D cardiac patches which will be functional closer to normal mammalian heart muscle and will also provide insight into the potential applicability of the cardiac patches in supporting functional recovery of failing myocardium.

Public Health Relevance

Cardiovascular disorders remain a major medical challenge with an urgent need to develop novel therapeutic options. In this study, cardiac patches will be fabricated and tested as a platform to support the recovery of infracted hearts. Successful completion of this study will result in the development of platform technology and provide a novel treatment modality for heart failure patients, benefiting millions of patients around the world.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
7R01EB011516-04
Application #
8411644
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Hunziker, Rosemarie
Project Start
2010-05-01
Project End
2014-03-31
Budget Start
2011-12-01
Budget End
2012-03-31
Support Year
4
Fiscal Year
2011
Total Cost
$149,004
Indirect Cost
Name
University of Houston
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
036837920
City
Houston
State
TX
Country
United States
Zip Code
77204
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Salazar, Betsy H; Hoffman, Kristopher A; Reddy, Anilkumar K et al. (2018) 16-Channel Flexible System to Measure Electrophysiological Properties of Bioengineered Hearts. Cardiovasc Eng Technol 9:94-104
Tao, Ze-Wei; Mohamed, Mohamed; Hogan, Matthew et al. (2017) Optimizing a spontaneously contracting heart tissue patch with rat neonatal cardiac cells on fibrin gel. J Tissue Eng Regen Med 11:153-163
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Patel, Nikita M; Birla, Ravi K (2016) Pulsatile flow conditioning of three-dimensional bioengineered cardiac ventricle. Biofabrication 9:015003
Patel, Nikita M; Yazdi, Iman K; Tasciotti, Ennio et al. (2016) Optimizing cell seeding and retention in a three-dimensional bioengineered cardiac ventricle: The two-stage cellularization model. Biotechnol Bioeng 113:2275-85
Mohamed, Mohamed A; Hogan, Matt K; Patel, Nikita M et al. (2015) Establishing the Framework for Tissue Engineered Heart Pumps. Cardiovasc Eng Technol 6:220-9
Salazar, Betsy H; Reddy, Anilkumar K; Zewei Tao et al. (2015) 32-Channel System to Measure the Electrophysiological Properties of Bioengineered Cardiac Muscle. IEEE Trans Biomed Eng 62:1614-22
Salazar, Betsy H; Cashion, Avery T; Dennis, Robert G et al. (2015) Development of a Cyclic Strain Bioreactor for Mechanical Enhancement and Assessment of Bioengineered Myocardial Constructs. Cardiovasc Eng Technol 6:533-45
Tao, Ze-Wei; Mohamed, Mohamed; Hogan, Matthew et al. (2015) Establishing the Framework for Fabrication of a Bioartificial Heart. ASAIO J 61:429-36

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