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

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dc.contributor.authorNavaee, Fatemeh
dc.contributor.authorRenaud, Philippe
dc.contributor.authorPiacentini, Niccolo
dc.contributor.authorDurand, Mathilde
dc.contributor.authorBayat, Dara Zaman
dc.contributor.authorLedroit, Diane
dc.contributor.authorBoder-Pasche, Stéphanie
dc.contributor.authorKleger, Alexander
dc.contributor.authorBraschler, Thomas
dc.contributor.authorWeder, Gilles
dc.date.accessioned2023-02-17T12:06:34Z
dc.date.available2023-02-17T12:06:34Z
dc.date.issued2023-02-17
dc.description.abstractMyocardium 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 dECMfibrin 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.en_US
dc.identifier.citationBioengineering 2023, 10, 266en_US
dc.identifier.doihttps://doi.org/10.3390/bioengineering10020266
dc.identifier.urihttps://hdl.handle.net/20.500.12839/1159
dc.language.isoenen_US
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectcardiac modelen_US
dc.subjecthelicoidal orientationen_US
dc.subject3D cell orientationen_US
dc.subjectmechanical stimulationen_US
dc.subjectsurface topographyen_US
dc.titleToward a Physiologically Relevant 3D Helicoidal-Oriented Cardiac Model: Simultaneous Application of Mechanical Stimulation and Surface Topographyen_US
dc.typeJournal Articleen_US
dc.type.csemdivisionsBU-Ten_US
dc.type.csemresearchareasTools for Life Sciencesen_US
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