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 - Bhattarai, Aroj A1 - Frotscher, Ralf A1 - Staat, Manfred T1 - Biomechanical study of the female pelvic floor dysfunction using the finite element method T2 - Conference proceedings of the YIC GACM 2015 : 3rd ECCOMAS Young Investigators Conference and 6th GACM Colloquium on Computational Mechanics , Aachen , Germany, 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 - 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 - 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 - 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 - Duong, Minh Tuan A1 - Jung, Alexander A1 - Frotscher, Ralf A1 - Staat, Manfred ED - Papadrakakis, M. T1 - A 3D electromechanical FEM-based model for cardiac tissue T2 - ECCOMAS Congress 2016, VII European Congress on Computational Methods in Applied Sciences and Engineering. Crete Island, Greece, 5–10 June 2016 Y1 - 2016 N1 - revised after the conference P11367 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 - CHAP A1 - Bhattarai, Aroj A1 - Frotscher, Ralf A1 - Staat, Manfred T1 - Computational Analysis of Pelvic Floor Dysfunction T2 - Women's Health and Biomechanics N2 - Pelvic floor dysfunction (PFD) is characterized by the failure of the levator ani (LA) muscle to maintain the pelvic hiatus, resulting in the descent of the pelvic organs below the pubococcygeal line. This chapter adopts the modified Humphrey material model to consider the effect of the muscle fiber on passive stretching of the LA muscle. The deformation of the LA muscle subjected to intra-abdominal pressure during Valsalva maneuver is compared with the magnetic resonance imaging (MRI) examination of a nulliparous female. Numerical result shows that the fiber-based Humphrey model simulates the muscle behavior better than isotropic constitutive models. Greater posterior movement of the LA muscle widens the levator hiatus due to lack of support from the anococcygeal ligament and the perineal structure as a consequence of birth-related injury and aging. Old and multiparous females with uncontrolled urogenital and rectal hiatus tend to develop PFDs such as prolapse and incontinence. KW - Pelvic muscle KW - Muscle fibers KW - Passive stretching KW - Pelvic floor dysfunction Y1 - 2018 SN - 978-3-319-71574-2 U6 - http://dx.doi.org/10.1007/978-3-319-71574-2_17 N1 - Lecture Notes in Computational Vision and Biomechanics, vol 29 SP - 217 EP - 230 PB - Springer CY - Cham 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 -