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Toward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topography

Myocardium consists of cardiac cells that interact with their environment through physical, biochemical, and electrical stimulations. The physiology, function, and metabolism of cardiac tissue are affected by this dynamic structure. Within the myocardium, cardiomyocytes’ orientations are parallel, c...

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Autores principales: Navaee, Fatemeh, Renaud, Philippe, Piacentini, Niccolò, Durand, Mathilde, Bayat, Dara Zaman, Ledroit, Diane, Heub, Sarah, Boder-Pasche, Stephanie, Kleger, Alexander, Braschler, Thomas, Weder, Gilles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952807/
https://www.ncbi.nlm.nih.gov/pubmed/36829760
http://dx.doi.org/10.3390/bioengineering10020266
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author Navaee, Fatemeh
Renaud, Philippe
Piacentini, Niccolò
Durand, Mathilde
Bayat, Dara Zaman
Ledroit, Diane
Heub, Sarah
Boder-Pasche, Stephanie
Kleger, Alexander
Braschler, Thomas
Weder, Gilles
author_facet Navaee, Fatemeh
Renaud, Philippe
Piacentini, Niccolò
Durand, Mathilde
Bayat, Dara Zaman
Ledroit, Diane
Heub, Sarah
Boder-Pasche, Stephanie
Kleger, Alexander
Braschler, Thomas
Weder, Gilles
author_sort Navaee, Fatemeh
collection PubMed
description Myocardium consists of cardiac cells that interact with their environment through physical, biochemical, and electrical stimulations. The physiology, function, and metabolism of cardiac tissue are affected by this dynamic structure. Within the myocardium, cardiomyocytes’ orientations are parallel, creating a dominant orientation. Additionally, local alignments of fibers, along with a helical organization, become evident at the macroscopic level. For the successful development of a reliable in vitro cardiac model, evaluation of cardiac cells’ behavior in a dynamic microenvironment, as well as their spatial architecture, is mandatory. In this study, we hypothesize that complex interactions between long-term contraction boundary conditions and cyclic mechanical stimulation may provide a physiological mechanism to generate off-axis alignments in the preferred mechanical stretch direction. This off-axis alignment can be engineered in vitro and, most importantly, mirrors the helical arrangements observed in vivo. For this purpose, uniaxial mechanical stretching of dECM-fibrin hydrogels was performed on pre-aligned 3D cultures of cardiac cells. In view of the potential development of helical structures similar to those in native hearts, the possibility of generating oblique alignments ranging between 0° and 90° was explored. Indeed, our investigations of cell alignment in 3D, employing both mechanical stimulation and groove constraint, provide a reliable mechanism for the generation of helicoidal structures in the myocardium. By combining cyclic stretch and geometric alignment in grooves, an intermediate angle toward favored direction can be achieved experimentally: while cyclic stretch produces a perpendicular orientation, geometric alignment is associated with a parallel one. In our 2D and 3D culture conditions, nonlinear cellular addition of the strains and strain avoidance concept reliably predicted the preferred cellular alignment. The 3D dECM-fibrin model system in this study shows that cyclical stretching supports cell survival and development. Using mechanical stimulation of pre-aligned heart cells, maturation markers are augmented in neonatal cardiomyocytes, while the beating culture period is prolonged, indicating an improved model function. We propose a simplified theoretical model based on numerical simulation and nonlinear strain avoidance by cells to explain oblique alignment angles. Thus, this work lays a possible rational basis for understanding and engineering oblique cellular alignments, such as the helicoidal layout of the heart, using approaches that simultaneously enhance maturation and function.
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spelling pubmed-99528072023-02-25 Toward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topography Navaee, Fatemeh Renaud, Philippe Piacentini, Niccolò Durand, Mathilde Bayat, Dara Zaman Ledroit, Diane Heub, Sarah Boder-Pasche, Stephanie Kleger, Alexander Braschler, Thomas Weder, Gilles Bioengineering (Basel) Article Myocardium consists of cardiac cells that interact with their environment through physical, biochemical, and electrical stimulations. The physiology, function, and metabolism of cardiac tissue are affected by this dynamic structure. Within the myocardium, cardiomyocytes’ orientations are parallel, creating a dominant orientation. Additionally, local alignments of fibers, along with a helical organization, become evident at the macroscopic level. For the successful development of a reliable in vitro cardiac model, evaluation of cardiac cells’ behavior in a dynamic microenvironment, as well as their spatial architecture, is mandatory. In this study, we hypothesize that complex interactions between long-term contraction boundary conditions and cyclic mechanical stimulation may provide a physiological mechanism to generate off-axis alignments in the preferred mechanical stretch direction. This off-axis alignment can be engineered in vitro and, most importantly, mirrors the helical arrangements observed in vivo. For this purpose, uniaxial mechanical stretching of dECM-fibrin hydrogels was performed on pre-aligned 3D cultures of cardiac cells. In view of the potential development of helical structures similar to those in native hearts, the possibility of generating oblique alignments ranging between 0° and 90° was explored. Indeed, our investigations of cell alignment in 3D, employing both mechanical stimulation and groove constraint, provide a reliable mechanism for the generation of helicoidal structures in the myocardium. By combining cyclic stretch and geometric alignment in grooves, an intermediate angle toward favored direction can be achieved experimentally: while cyclic stretch produces a perpendicular orientation, geometric alignment is associated with a parallel one. In our 2D and 3D culture conditions, nonlinear cellular addition of the strains and strain avoidance concept reliably predicted the preferred cellular alignment. The 3D dECM-fibrin model system in this study shows that cyclical stretching supports cell survival and development. Using mechanical stimulation of pre-aligned heart cells, maturation markers are augmented in neonatal cardiomyocytes, while the beating culture period is prolonged, indicating an improved model function. We propose a simplified theoretical model based on numerical simulation and nonlinear strain avoidance by cells to explain oblique alignment angles. Thus, this work lays a possible rational basis for understanding and engineering oblique cellular alignments, such as the helicoidal layout of the heart, using approaches that simultaneously enhance maturation and function. MDPI 2023-02-17 /pmc/articles/PMC9952807/ /pubmed/36829760 http://dx.doi.org/10.3390/bioengineering10020266 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Navaee, Fatemeh
Renaud, Philippe
Piacentini, Niccolò
Durand, Mathilde
Bayat, Dara Zaman
Ledroit, Diane
Heub, Sarah
Boder-Pasche, Stephanie
Kleger, Alexander
Braschler, Thomas
Weder, Gilles
Toward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topography
title Toward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topography
title_full Toward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topography
title_fullStr Toward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topography
title_full_unstemmed Toward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topography
title_short Toward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topography
title_sort toward a physiologically relevant 3d helicoidal-oriented cardiac model: simultaneous application of mechanical stimulation and surface topography
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952807/
https://www.ncbi.nlm.nih.gov/pubmed/36829760
http://dx.doi.org/10.3390/bioengineering10020266
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