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 - 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 - Goßmann, Matthias A1 - Temiz Artmann, Aysegül A1 - Staat, Manfred T1 - Simulation of cardiac cell-seeded membranes using the edge-based smoothed FEM T2 - 1st International Conference "Shell and Membrane Theories in Mechanics and Biology: From Macro- to Nanoscale Structures", Minsk, Belarus, Sept. 16-20, 2013 Y1 - 2013 SN - 978-985-553-135-8 SP - 165 EP - 167 PB - Verl. d. Weißruss. Staatl. Univ. CY - Minsk ER - TY - CHAP A1 - Frotscher, Ralf A1 - Goßmann, Matthias A1 - Raatschen, Hans-Jürgen A1 - Temiz Artmann, Aysegül A1 - Staat, Manfred T1 - Simulation of cardiac cell-seeded membranes using the edge-based smoothed FEM T2 - Shell and membrane theories in mechanics and biology. (Advanced structured materials ; 45) N2 - We present an electromechanically coupled Finite Element model for cardiac tissue. It bases on the mechanical model for cardiac tissue of Hunter et al. that we couple to the McAllister-Noble-Tsien electrophysiological model of purkinje fibre cells. The corresponding system of ordinary differential equations is implemented on the level of the constitutive equations in a geometrically and physically nonlinear version of the so-called edge-based smoothed FEM for plates. Mechanical material parameters are determined from our own pressure-deflection experimental setup. The main purpose of the model is to further examine the experimental results not only on mechanical but also on electrophysiological level down to ion channel gates. Moreover, we present first drug treatment simulations and validate the model with respect to the experiments. Y1 - 2015 SN - 978-3-319-02534-6 ; 978-3-319-02535-3 SP - 187 EP - 212 PB - Springer CY - Heidelberg ER - TY - CHAP A1 - Frotscher, Ralf A1 - Duong, Minh Tuan A1 - Staat, Manfred T1 - Simulating beating cardiomyocytes with electromechanical coupling T2 - II. International Conference on Biomedical Technology : 28-30 October 2015 Hannover, Germany / T. Lenarz, P. Wriggers (Eds.) Y1 - 2015 SP - 1 EP - 2 ER - TY - CHAP A1 - Bhattarai, Aroj A1 - Frotscher, Ralf A1 - Staat, Manfred ED - Natal Jorge, Renato T1 - Significance of fibre geometry on passive-active response of pelvic muscles to evaluate pelvic dysfunction T2 - BioMedWomen: Proceedings of the international conference on clinical and bioengineering for women's health Y1 - 2016 SN - 978-1-138-02910-1 SP - 185 EP - 188 PB - CRC Press CY - Boca Raton 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 - JOUR A1 - Staat, Manfred A1 - Trenz, Eva A1 - Lohmann, Philipp A1 - Frotscher, Ralf A1 - Klinge, Uwe A1 - Tabaza, Ruth A1 - Kirschner-Hermanns, Ruth T1 - New measurements to compare soft tissue anchoring systems in pelvic floor surgery JF - Journal of Biomedical Materials Research Part B: Applied Biomaterials N2 - Suburethral slings as well as different meshes are widely used treating stress urinary incontinence and prolaps in women. With the development of MiniSlings and special meshes using less alloplastic material anchorage systems become more important to keep devices in place and to put some tension especially on the MiniSlings. To date, there are many different systems of MiniSlings of different companies on the market which differ in the structure of the used meshes and anchors. A new objective measurement method to compare different properties of MiniSling systems (mesh and anchor) is presented in this article. Ballistic gelatine acts as soft tissue surrogate. Significant differences in parameters like pull-out strength of anchors or shrinkage of meshes under loading conditions have been determined. The form and size of the anchors as well as the structural stability of the meshes are decisive for a proper integration. The tested anchorings sytems showed markedly different mechanical function at their respective load bearing capacity. As the stable fixation of the device in tissue is a prerequisite for a permanet reinforcement, the proposed test system permits further optimisation of anchor and mesh devices to improve the success of the surgical treatment Y1 - 2012 U6 - http://dx.doi.org/10.1002/jbm.b.32654 SN - 1552-4981 VL - 100B IS - 4 SP - 924 EP - 933 PB - Wiley CY - Hoboken, NJ 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 - 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 -