Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

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Abstract

Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction.

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The inflammatory response in myocardial infarction.

Nikolaos G Frangogiannis, C. Smith, Mark L. Entman (2002)

One of the major therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair following myocardial infarction. However, a sound understanding of the biology is necessary before a specific intervention is pursued on a therapeutic basis. This review summarizes our current understanding of the cellular and molecular mechanisms regulating the inflammatory response following myocardial ischemia and reperfusion. Myocardial necrosis induces complement activation and free radical generation, triggering a cytokine cascade initiated by Tumor Necrosis Factor (TNF)-alpha release. If reperfusion of the infarcted area is initiated, it is attended by an intense inflammatory reaction. Interleukin (IL)-8 synthesis and C5a activation have a crucial role in recruiting neutrophils in the ischemic and reperfused myocardium. Neutrophil infiltration is regulated through a complex sequence of molecular steps involving the selectins and the integrins, which mediate leukocyte rolling and adhesion to the endothelium. Marginated neutrophils exert potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. Despite this potential injury, substantial evidence suggests that reperfusion enhances cardiac repair improving patient survival; this effect may be in part related to the inflammatory response. Monocyte Chemoattractant Protein (MCP)-1 is also markedly upregulated in the infarcted myocardium inducing recruitment of mononuclear cells in the injured areas. Monocyte-derived macrophages and mast cells may produce cytokines and growth factors necessary for fibroblast proliferation and neovascularization, leading to effective repair and scar formation. At this stage expression of inhibitory cytokines such as IL-10 may have a role in suppressing the acute inflammatory response and in regulating extracellular matrix metabolism. Fibroblasts in the healing scar undergo phenotypic changes expressing smooth muscle cell markers. Our previous review in this journal focused almost exclusively on reduction of the inflammatory injury. The current update is prompted by the potential therapeutic opportunity that the open vessel offers. By promoting more effective tissue repair, it may be possible to reduce the deleterious remodeling, that is the leading cause of heart failure and death. Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction.

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Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts.

Wolfram-Hubertus Zimmermann, Ivan Melnychenko, Gerald Wasmeier … (2006)

The concept of regenerating diseased myocardium by implantation of tissue-engineered heart muscle is intriguing, but convincing evidence is lacking that heart tissues can be generated at a size and with contractile properties that would lend considerable support to failing hearts. Here we created large (thickness/diameter, 1-4 mm/15 mm), force-generating engineered heart tissue from neonatal rat heart cells. Engineered heart tissue formed thick cardiac muscle layers when implanted on myocardial infarcts in immune-suppressed rats. When evaluated 28 d later, engineered heart tissue showed undelayed electrical coupling to the native myocardium without evidence of arrhythmia induction. Moreover, engineered heart tissue prevented further dilation, induced systolic wall thickening of infarcted myocardial segments and improved fractional area shortening of infarcted hearts compared to controls (sham operation and noncontractile constructs). Thus, our study provides evidence that large contractile cardiac tissue grafts can be constructed in vitro, can survive after implantation and can support contractile function of infarcted hearts.

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Carbon nanotubes: synthesis, integration, and properties.

Hongjie Dai (2002)

Synthesis of carbon nanotubes by chemical vapor deposition over patterned catalyst arrays leads to nanotubes grown from specific sites on surfaces. The growth directions of the nanotubes can be controlled by van der Waals self-assembly forces and applied electric fields. The patterned growth approach is feasible with discrete catalytic nanoparticles and scalable on large wafers for massive arrays of novel nanowires. Controlled synthesis of nanotubes opens up exciting opportunities in nanoscience and nanotechnology, including electrical, mechanical, and electromechanical properties and devices, chemical functionalization, surface chemistry and photochemistry, molecular sensors, and interfacing with soft biological systems.

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Author and article information

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group

ISSN (Electronic): 2045-2322

Publication date (Electronic): 16 January 2014

Publication date Collection: 2014

Volume: 4

Electronic Location Identifier: 3733

Affiliations

[1 ]Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center , 27 Taiping Rd, Academy of Military Medical Sciences, Beijing, China

[2 ]Department of Mechanical and Manufacturing Engineering, Faculty of Engineering, Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba and Manitoba Institute of Child Health , Winnipeg, Manitoba, Canada

[3 ]Department of Anatomy, Southern Medical University , Guangzhou Guangdong, China

[4 ]Department of Textile Sciences, Faculty of Human Ecology, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba , Canada

[5 ]Department of Biomedical Engineering, College of Engineering, 5 Yiheyuan Rd, Peking University , HaidianDist, Beijing, China

[6 ]These authors contributed equally to this work.

Author notes

[a ] wangchy@ 123456bmi.ac.cn

[b ] xing@ 123456cc.umanitoba.ca

Article

Publisher Item ID: srep03733

DOI: 10.1038/srep03733

PMC ID: 3893643

PubMed ID: 24429673

SO-VID: cd8ef02d-b052-400b-bc5f-0d4615e4b75a

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

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Photoluminescent Nanomaterials

Most cited references 40

The inflammatory response in myocardial infarction.

Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts.

Carbon nanotubes: synthesis, integration, and properties.

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