Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular applications

David A Stout,1,2 Jennie Yoo,2 Adriana Noemi Santiago-Miranda,3 Thomas J Webster1,41School of Engineering, 2Division of Biology and Medicine, Brown University, Providence, RI, 3Department of Chemical Engineering, University of Puerto Rico, Mayag&uuml;es, PR, 4Department of Orthopedics, Brown...

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Autores principales:	Stout DA, Yoo J, Noemi Santiago-Miranda A, Webster TJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/425b273c9a3e4710b1b8b1d6caf13558
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spelling	oai:doaj.org-article:425b273c9a3e4710b1b8b1d6caf135582021-12-02T06:04:01ZMechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular applications1176-91141178-2013https://doaj.org/article/425b273c9a3e4710b1b8b1d6caf135582012-11-01T00:00:00Zhttp://www.dovepress.com/mechanisms-of-greater-cardiomyocyte-functions-on-conductive-nanoengine-a11519https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013David A Stout,1,2 Jennie Yoo,2 Adriana Noemi Santiago-Miranda,3 Thomas J Webster1,41School of Engineering, 2Division of Biology and Medicine, Brown University, Providence, RI, 3Department of Chemical Engineering, University of Puerto Rico, Mayag&uuml;es, PR, 4Department of Orthopedics, Brown University, Providence, RI, USABackground: Recent advances in nanotechnology (materials with at least one dimension between 1 nm and 100 nm) have led to the use of nanomaterials in numerous medical device applications. Recently, nanomaterials have been used to create innovative biomaterials for cardiovascular applications. Specifically, carbon nanofibers (CNF) embedded in poly(lactic-co-glycolic-acid) (PLGA) have been shown to promote cardiomyocyte growth compared with conventional polymer substrates, but the mechanisms involved in such events remain unknown. The aim of this study was to determine the basic mechanism of cell growth on these novel nanocomposites.Methods: CNF were added to biodegradable PLGA (50:50 PGA:PLA weight ratio) to increase the conductivity, mechanical and cytocompatibility properties of pure PLGA. For this reason, different PLGA to CNF ratios (100:0, 75:25, 50:50, 25:75, and 0:100 wt%) with different PLGA densities (0.1, 0.05, 0.025, and 0.0125 g/mL) were used, and their compatibility with cardiomyocytes was assessed.Results: Throughout all the cytocompatibility experiments, cardiomyocytes were viable and expressed important biomarkers, including cardiac troponin T, connexin-43, and alpha-sarcomeric actin (&alpha;-SCA). Adhesion and proliferation experiments indicated that a PLGA density of 0.025 g/mL with a PLGA to CNF ratio of 75:25 and 50:50 (wt%) promoted the best overall cell growth, ie, a 55% increase in cardiomyocyte density after 120 hours compared with pure PLGA and a 75% increase compared with the control at the same time point for 50:50 (wt%). The PLGA:CNF materials were conductive, and their conductivity increased as greater amounts of CNF were added to pure PLGA, from 0 S &bull; m-1 for pure PLGA (100:0 wt%) to 5.5 &times; 10-3 S &bull; m-1 for pure CNF (0:100 wt%), as compared with natural heart tissue (ranging from 0.16 S &bull; m-1 longitudinally to 0.005 S &bull; m-1 transversely). Tensile tests showed that the addition of CNF increased the tensile strength to mimic that of natural heart tissue, ie, 0.15 MPa for 100% PLGA to 5.41 MPa for the 50:50 (PLGA to CNF [wt%:wt%]) ratio at 0.025 g/mL. Atomic force microscopy indicated that the addition of CNF to PLGA increased the material surface area from 10% (100:0 [PLGA to carbon nanofiber (wt%:wt%)]) to over 60% (50:50 [PLGA to carbon nanofibers (wt%:wt%)]). Lastly, the adsorption of specific proteins (fibronectin and vitronectin) showed significantly more adsorption for the 50:50 PLGA to CNF (wt%:wt%) ratio at 0.025 g/mL PLGA compared with pure PLGA, which may be why cardiomyocyte function increased on CNF-enriched composites.Conclusion: This study demonstrates that cardiomyocyte function was enhanced on 50:50 PLGA to CNF (wt%:wt%) composite ratios at 0.025 g/mL PLGA densities because they mimicked native heart tissue tensile strength/conductivity and increased the adsorption of proteins known to promote cardiomyocyte function.Keywords: cardiomyocytes, poly(lactic-co-glycolic acid), carbon nanofibers, nanoroughness, protein adsorption, conductive, nanotechnologyStout DAYoo JNoemi Santiago-Miranda AWebster TJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5653-5669 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Stout DA Yoo J Noemi Santiago-Miranda A Webster TJ Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular applications
description	David A Stout,1,2 Jennie Yoo,2 Adriana Noemi Santiago-Miranda,3 Thomas J Webster1,41School of Engineering, 2Division of Biology and Medicine, Brown University, Providence, RI, 3Department of Chemical Engineering, University of Puerto Rico, Mayag&uuml;es, PR, 4Department of Orthopedics, Brown University, Providence, RI, USABackground: Recent advances in nanotechnology (materials with at least one dimension between 1 nm and 100 nm) have led to the use of nanomaterials in numerous medical device applications. Recently, nanomaterials have been used to create innovative biomaterials for cardiovascular applications. Specifically, carbon nanofibers (CNF) embedded in poly(lactic-co-glycolic-acid) (PLGA) have been shown to promote cardiomyocyte growth compared with conventional polymer substrates, but the mechanisms involved in such events remain unknown. The aim of this study was to determine the basic mechanism of cell growth on these novel nanocomposites.Methods: CNF were added to biodegradable PLGA (50:50 PGA:PLA weight ratio) to increase the conductivity, mechanical and cytocompatibility properties of pure PLGA. For this reason, different PLGA to CNF ratios (100:0, 75:25, 50:50, 25:75, and 0:100 wt%) with different PLGA densities (0.1, 0.05, 0.025, and 0.0125 g/mL) were used, and their compatibility with cardiomyocytes was assessed.Results: Throughout all the cytocompatibility experiments, cardiomyocytes were viable and expressed important biomarkers, including cardiac troponin T, connexin-43, and alpha-sarcomeric actin (&alpha;-SCA). Adhesion and proliferation experiments indicated that a PLGA density of 0.025 g/mL with a PLGA to CNF ratio of 75:25 and 50:50 (wt%) promoted the best overall cell growth, ie, a 55% increase in cardiomyocyte density after 120 hours compared with pure PLGA and a 75% increase compared with the control at the same time point for 50:50 (wt%). The PLGA:CNF materials were conductive, and their conductivity increased as greater amounts of CNF were added to pure PLGA, from 0 S &bull; m-1 for pure PLGA (100:0 wt%) to 5.5 &times; 10-3 S &bull; m-1 for pure CNF (0:100 wt%), as compared with natural heart tissue (ranging from 0.16 S &bull; m-1 longitudinally to 0.005 S &bull; m-1 transversely). Tensile tests showed that the addition of CNF increased the tensile strength to mimic that of natural heart tissue, ie, 0.15 MPa for 100% PLGA to 5.41 MPa for the 50:50 (PLGA to CNF [wt%:wt%]) ratio at 0.025 g/mL. Atomic force microscopy indicated that the addition of CNF to PLGA increased the material surface area from 10% (100:0 [PLGA to carbon nanofiber (wt%:wt%)]) to over 60% (50:50 [PLGA to carbon nanofibers (wt%:wt%)]). Lastly, the adsorption of specific proteins (fibronectin and vitronectin) showed significantly more adsorption for the 50:50 PLGA to CNF (wt%:wt%) ratio at 0.025 g/mL PLGA compared with pure PLGA, which may be why cardiomyocyte function increased on CNF-enriched composites.Conclusion: This study demonstrates that cardiomyocyte function was enhanced on 50:50 PLGA to CNF (wt%:wt%) composite ratios at 0.025 g/mL PLGA densities because they mimicked native heart tissue tensile strength/conductivity and increased the adsorption of proteins known to promote cardiomyocyte function.Keywords: cardiomyocytes, poly(lactic-co-glycolic acid), carbon nanofibers, nanoroughness, protein adsorption, conductive, nanotechnology
format	article
author	Stout DA Yoo J Noemi Santiago-Miranda A Webster TJ
author_facet	Stout DA Yoo J Noemi Santiago-Miranda A Webster TJ
author_sort	Stout DA
title	Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular applications
title_short	Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular applications
title_full	Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular applications
title_fullStr	Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular applications
title_full_unstemmed	Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular applications
title_sort	mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular applications
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/425b273c9a3e4710b1b8b1d6caf13558
work_keys_str_mv	AT stoutda mechanismsofgreatercardiomyocytefunctionsonconductivenanoengineeredcompositesforcardiovascularapplications AT yooj mechanismsofgreatercardiomyocytefunctionsonconductivenanoengineeredcompositesforcardiovascularapplications AT noemisantiagomirandaa mechanismsofgreatercardiomyocytefunctionsonconductivenanoengineeredcompositesforcardiovascularapplications AT webstertj mechanismsofgreatercardiomyocytefunctionsonconductivenanoengineeredcompositesforcardiovascularapplications
_version_	1718400047717023744

Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular applications

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