Sample-specific adaption of an improved electro-mechanical model of in vitro cardiac tissue

Frotscher, Ralf; Muanghong, Danita; Dursun, Gözde; Goßmann, Matthias; Artmann, A.; Staat, Manfred

doi:10.1016/j.jbiomech.2016.01.039

Cited by 12 publications

(18 citation statements)

References 28 publications

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“…Details including basic equations and additional simulations are presented in [42][43][44]. Parameter fittings and other statistical assessments related to the simulations have been performed in the statistics software R and in Scilab.…”

Section: Mathematical Modeling and Computer Simulationsmentioning

confidence: 99%

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Goßmann

Frotscher

Linder³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.

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Section: Mathematical Modeling and Computer Simulationsmentioning

confidence: 99%

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Goßmann

Frotscher

Linder³

et al. 2016

Cell Physiol Biochem

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“…X Pa is necessary to displace the central point of the 2D 19 μm model to 1.2 mm. This has been experimentally validated [14]. Displacements are then projected onto the 3D electrical mesh.…”

Section: Finite Element Modelsmentioning

confidence: 99%

“…Displacements are then projected onto the 3D electrical mesh. Subsequently, the autonomous cell contractions is simulated using an algorithm to solve the electromechanical problem which is described in [14]. When using the same mesh for the mechanical and the electrical part, the displacements do no longer need to be projected.…”

Section: Finite Element Modelsmentioning

confidence: 99%

“…Here, the electrophysiology is modeled on the cellular level [11][12][13][14][15] or is simplified using eikonal equations [16] or the FitzHugh-Nagumo model [17,18]. There exist a wide range of electromechanical models from the cell [10,12] over the tissue [14] to the organ level including left ventricular models [11,15], models of both ventricles [12][13][14][15]17], and whole heart models [18]. They feature a varying degree of complexity with respect to the anatomical representation, associated mesh fineness, boundary conditions, material models, underlying electrophysiological models and coupling models depending on the research objective.…”

Section: Introductionmentioning

confidence: 99%

“…Drugs have already been applied to the culture medium leading to phenomenologically observable changes in the beating frequency, deflection, contraction duration, activation time, relaxation time and resting time [25]. Frotscher et al [14,26,27] developed an electromechanical model of the CellDrum which they parametrized, verified and validated using respective experiments. On the level of the electrophysiological cell models also the drug action was implemented.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A 3d Electromechanical Fem-Based Model for Cardiac Tissue

Dương¹,

Jung²,

Frotscher³

et al. 2016

Proceedings of the VII European Congress on Computational Methods in Applied Sciences and Engineering (ECCOMAS Congress 2016)

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Mechanical Characterization of hiPSC‐Derived Cardiac Tissues for Quality Control

et al. 2018

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Heart disease is one of the leading death causes in developed countries. To facilitate heart rehabilitation, engineered cardiac implantation has emerged as a promising alternative to organ transplantation. Currently there is no quantitative standard to ensure the safety and functionality of the engineered cardiac tissues intended for clinical uses. In anticipation of the clinical application of the engineered cardiac tissues to heart disease patients, a suite of methods is assembled to evaluate the mechanical characteristics critical to cardiac functions, including contractility, viscoelasticity, and dynamic stress distribution. As a proof of concept, 3D bioprinted cardiac tissues derived from human induced pluripotent stem cells are tested. First, the engineered cardiac tissues labeled with particles are recorded and tracked to determine spatially and temporally variable contraction forces. Viscoelastic properties are measured using magnetic tweezers. The results are used to compute 3D force and stress distribution over the engineered tissue by finite element method. In summary, a framework is developed to assess clinical‐grade engineered cardiac tissues and determine the appropriate value ranges suitable for implantation. The results relating contractility, intrinsic mechanical properties, and stress distribution in the engineered tissue, can also inform better design for future fabrication of engineered tissues.

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Sample-specific adaption of an improved electro-mechanical model of in vitro cardiac tissue

Cited by 12 publications

References 28 publications

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

A 3d Electromechanical Fem-Based Model for Cardiac Tissue

Mechanical Characterization of hiPSC‐Derived Cardiac Tissues for Quality Control

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