TY - JOUR A1 - Frotscher, Ralf A1 - Koch, Jan-Peter A1 - Staat, Manfred T1 - Computational investigation of drug action on human-induced stem cell derived cardiomyocytes JF - Journal of biomechanical engineering Y1 - 2015 U6 - http://dx.doi.org/10.1115/1.4030173 SN - 1528-8951 (E-Journal); 0148-0731 (Print) VL - Vol. 137 IS - iss. 7 SP - 071002-1 EP - 071002-7 PB - ASME CY - New York ER - TY - JOUR A1 - Frotscher, Ralf A1 - Muanghong, Danita A1 - Dursun, Gözde A1 - Goßmann, Matthias A1 - Temiz Artmann, Aysegül A1 - Staat, Manfred T1 - Sample-specific adaption of an improved electro-mechanical model of in vitro cardiac tissue JF - Journal of Biomechanics N2 - We present an electromechanically coupled computational model for the investigation of a thin cardiac tissue construct consisting of human-induced pluripotent stem cell-derived atrial, ventricular and sinoatrial cardiomyocytes. The mechanical and electrophysiological parts of the finite element model, as well as their coupling are explained in detail. The model is implemented in the open source finite element code Code_Aster and is employed for the simulation of a thin circular membrane deflected by a monolayer of autonomously beating, circular, thin cardiac tissue. Two cardio-active drugs, S-Bay K8644 and veratridine, are applied in experiments and simulations and are investigated with respect to their chronotropic effects on the tissue. These results demonstrate the potential of coupled micro- and macroscopic electromechanical models of cardiac tissue to be adapted to experimental results at the cellular level. Further model improvements are discussed taking into account experimentally measurable quantities that can easily be extracted from the obtained experimental results. The goal is to estimate the potential to adapt the presented model to sample specific cell cultures. KW - hiPS cardiomyocytes KW - Homogenization KW - Hodgkin–Huxley models KW - Frequency adaption KW - Electromechanical modeling KW - Drug simulation KW - Computational biomechanics KW - Cardiac tissue Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.jbiomech.2016.01.039 SN - 0021-9290 (Print) SN - 1873-2380 (Online) VL - 49 IS - 12 SP - 2428 EP - 2435 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Frotscher, Ralf A1 - Raatschen, Hans-Jürgen A1 - Staat, Manfred ED - Eberhardsteiner, J. T1 - Application of an edge-based smoothed finite element method on geometrically non-linear plates of non-linear material T2 - Proceedings European Congress on Computational Methods in Applied Sciences and Engineering (ECCOMAS 2012) Y1 - 2012 N1 - 6th European Congress on Computational Methods in Applied Sciences and Engineering (ECCOMAS 2012) Vienna, Austria, September 10-14, 2012 ER - TY - CHAP A1 - Frotscher, Ralf A1 - Raatschen, Hans-Jürgen A1 - Staat, Manfred ED - Holzapfel, Gerhard A. T1 - Effectiveness of the edge-based smoothed finite element method applied to soft biological tissues T2 - ESMC-2012 - 8th European Solid Mechanics Conference, Graz, Austria, July 9-13, 2012 Y1 - 2012 SN - 978-3-85125-223-1 PB - Verlag d. Technischen Universität Graz CY - Graz ER - TY - JOUR A1 - Frotscher, Ralf A1 - Staat, Manfred T1 - Stresses produced by different textile mesh implants in a tissue equivalent JF - BioNanoMaterials N2 - Two single-incision mini-slings used for treating urinary incontinence in women are compared with respect to the stresses they produce in their surrounding tissue. In an earlier paper we experimentally observed that these implants produce considerably different stress distributions in a muscle tissue equivalent. Here we perform 2D finite element analyses to compare the shear stresses and normal stresses in the tissue equivalent for the two meshes and to investigate their failure behavior. The results clearly show that the Gynecare TVT fails for increasing loads in a zipper-like manner because it gradually debonds from the surrounding tissue. Contrary to that, the tissue at the ends of the DynaMesh-SIS direct may rupture but only at higher loads. The simulation results are in good agreement with the experimental observations thus the computational model helps to interpret the experimental results and provides a tool for qualitative evaluation of mesh implants. Y1 - 2014 U6 - http://dx.doi.org/10.1515/bnm-2014-0003 SN - 2191-4672 (E-Journal); 2193-066X (E-Journal); 0011-8656 (Print); 1616-0177 (Print); 2193-0651 (Print) VL - 15 IS - 1-2 SP - 25 EP - 30 PB - De Gruyter CY - Berlin ER - TY - CHAP A1 - Frotscher, Ralf A1 - Staat, Manfred T1 - An electromechanical model for cardiac tissue constructs T2 - Conference proceedings of the YIC GACM 2015 : 3rd ECCOMAS Young Investigators Conference and 6th GACM Colloquium on Computational Mechanics , Aachen, 20.07.2015 - 23.07.2015 / ed.: Stefanie Elgeti ; Jaan-Willem Simon Y1 - 2015 SP - 1 EP - 4 PB - RWTH Aachen University CY - Aachen ER - TY - CHAP A1 - Frotscher, Ralf A1 - Staat, Manfred ED - Nithiarasu, Perumal T1 - Homogenization of a cardiac tissue construct T2 - CMBE15 : 4th International Conference on Computational & Mathematical Biomedical Engineering ; 29th June - 1st July 2015 ; École Normale Supérieure de Cachan ; Cachan (Paris), France Y1 - 2015 SN - 2227-9385 N1 - Konferenzband unter: http://www.compbiomed.net/getfile.php?type=12/site_documents&id=Proceedings_2227-9385_compressed.pdf SP - 645 EP - 648 PB - CMBE CY - [s.l.] ER - TY - CHAP A1 - Frotscher, Ralf A1 - Staat, Manfred ED - Artmann, Gerhard ED - Temiz Artmann, Aysegül ED - Zhubanova, Azhar A. ED - Digel, Ilya T1 - Towards Patient-Specific Computational Modeling of hiPS-Derived Cardiomyocyte Function and Drug Action T2 - Biological, Physical and Technical Basics of Cell Engineering N2 - Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) today are widely used for the investigation of normal electromechanical cardiac function, of cardiac medication and of mutations. Computational models are thus established that simulate the behavior of this kind of cells. This section first motivates the modeling of hiPS-CM and then presents and discusses several modeling approaches of microscopic and macroscopic constituents of human-induced pluripotent stem cell-derived and mature human cardiac tissue. The focus is led on the mapping of the computational results one can achieve with these models onto mature human cardiomyocyte models, the latter being the real matter of interest. Model adaptivity is the key feature that is discussed because it opens the way for modeling various biological effects like biological variability, medication, mutation and phenotypical expression. We compare the computational with experimental results with respect to normal cardiac function and with respect to inotropic and chronotropic drug effects. The section closes with a discussion on the status quo of the specificity of computational models and on what challenges have to be solved to reach patient-specificity. Y1 - 2018 SN - 978-981-10-7904-7 U6 - http://dx.doi.org/10.1007/978-981-10-7904-7_10 SP - 233 EP - 250 PB - Springer CY - Singapore ER - TY - JOUR A1 - Goßmann, Matthias A1 - Frotscher, Ralf A1 - Linder, Peter A1 - Bayer, Robin A1 - Epple, U. A1 - Staat, Manfred A1 - Temiz Artmann, Aysegül A1 - Artmann, Gerhard T1 - Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells JF - Cellular physiology and biochemistry N2 - 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. KW - Inotropic compounds KW - Pharmacology KW - Ion channels KW - CellDrum KW - Heart tissue culture KW - Induced pluripotent stem cells KW - Cardiac myocytes Y1 - 2016 U6 - http://dx.doi.org/10.1159/000443124 SN - 1421-9778 (Online) SN - 1015-8987 (Print) VL - 38 IS - 3 SP - 1182 EP - 1198 PB - Karger CY - Basel ER - TY - CHAP A1 - Jung, Alexander A1 - Frotscher, Ralf A1 - Staat, Manfred T1 - Electromechanical model of hiPSC-derived ventricular cardiomyocytes cocultured with fibroblasts T2 - 6th European Conference on Computational Mechanics (ECCM 6), 7th European Conference on Computational Fluid Dynamics (ECFD 7), 11-15 June 2018, Glasgow, UK N2 - The CellDrum provides an experimental setup to study the mechanical effects of fibroblasts co-cultured with hiPSC-derived ventricular cardiomyocytes. Multi-scale computational models based on the Finite Element Method are developed. Coupled electrical cardiomyocyte-fibroblast models (cell level) are embedded into reaction-diffusion equations (tissue level) which compute the propagation of the action potential in the cardiac tissue. Electromechanical coupling is realised by an excitation-contraction model (cell level) and the active stress arising during contraction is added to the passive stress in the force balance, which determines the tissue displacement (tissue level). Tissue parameters in the model can be identified experimentally to the specific sample. Y1 - 2018 ER -