@article{ColomboDriraFrotscheretal.2022, author = {Colombo, Daniele and Drira, Slah and Frotscher, Ralf and Staat, Manfred}, title = {An element-based formulation for ES-FEM and FS-FEM models for implementation in standard solid mechanics finite element codes for 2D and 3D static analysis}, series = {International Journal for Numerical Methods in Engineering}, volume = {124}, journal = {International Journal for Numerical Methods in Engineering}, number = {2}, publisher = {Wiley}, address = {Chichester}, issn = {1097-0207}, doi = {10.1002/nme.7126}, pages = {402 -- 433}, year = {2022}, abstract = {Edge-based and face-based smoothed finite element methods (ES-FEM and FS-FEM, respectively) are modified versions of the finite element method allowing to achieve more accurate results and to reduce sensitivity to mesh distortion, at least for linear elements. These properties make the two methods very attractive. However, their implementation in a standard finite element code is nontrivial because it requires heavy and extensive modifications to the code architecture. In this article, we present an element-based formulation of ES-FEM and FS-FEM methods allowing to implement the two methods in a standard finite element code with no modifications to its architecture. Moreover, the element-based formulation permits to easily manage any type of element, especially in 3D models where, to the best of the authors' knowledge, only tetrahedral elements are used in FS-FEM applications found in the literature. Shape functions for non-simplex 3D elements are proposed in order to apply FS-FEM to any standard finite element.}, language = {en} } @phdthesis{Frotscher2016, author = {Frotscher, Ralf}, title = {Electromechanical modeling and simulation of thin cardiac tissue constructs - smoothed FEM applied to a biomechanical plate problem}, year = {2016}, language = {en} } @techreport{BhattaraiFrotscherDurongetal.2016, author = {Bhattarai, Aroj and Frotscher, Ralf and Durong, Minh Tu{\´a}n and Staat, Manfred}, title = {Schlussbericht zu BINGO. Optimierung des Systems Netzimplantat-Beckenboden zur therapeutischen Gewebeverst{\"a}rkung nach der Integraltheorie.}, address = {Aachen}, pages = {34}, year = {2016}, language = {de} } @inproceedings{JungFrotscherStaat2018, author = {Jung, Alexander and Frotscher, Ralf and Staat, Manfred}, title = {Electromechanical model of hiPSC-derived ventricular cardiomyocytes cocultured with fibroblasts}, series = {6th European Conference on Computational Mechanics (ECCM 6), 7th European Conference on Computational Fluid Dynamics (ECFD 7), 11-15 June 2018, Glasgow, UK}, booktitle = {6th European Conference on Computational Mechanics (ECCM 6), 7th European Conference on Computational Fluid Dynamics (ECFD 7), 11-15 June 2018, Glasgow, UK}, pages = {11 Seiten}, year = {2018}, abstract = {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.}, language = {en} } @incollection{FrotscherStaat2018, author = {Frotscher, Ralf and Staat, Manfred}, title = {Towards Patient-Specific Computational Modeling of hiPS-Derived Cardiomyocyte Function and Drug Action}, series = {Biological, Physical and Technical Basics of Cell Engineering}, booktitle = {Biological, Physical and Technical Basics of Cell Engineering}, editor = {Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l and Zhubanova, Azhar A. and Digel, Ilya}, publisher = {Springer}, address = {Singapore}, isbn = {978-981-10-7904-7}, doi = {10.1007/978-981-10-7904-7_10}, pages = {233 -- 250}, year = {2018}, abstract = {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.}, language = {en} } @incollection{BhattaraiFrotscherStaat2018, author = {Bhattarai, Aroj and Frotscher, Ralf and Staat, Manfred}, title = {Computational Analysis of Pelvic Floor Dysfunction}, series = {Women's Health and Biomechanics}, booktitle = {Women's Health and Biomechanics}, publisher = {Springer}, address = {Cham}, isbn = {978-3-319-71574-2}, doi = {10.1007/978-3-319-71574-2_17}, pages = {217 -- 230}, year = {2018}, abstract = {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.}, language = {en} } @inproceedings{BhattaraiFrotscherStaat2016, author = {Bhattarai, Aroj and Frotscher, Ralf and Staat, Manfred}, title = {Significance of fibre geometry on passive-active response of pelvic muscles to evaluate pelvic dysfunction}, series = {BioMedWomen: Proceedings of the international conference on clinical and bioengineering for women's health}, booktitle = {BioMedWomen: Proceedings of the international conference on clinical and bioengineering for women's health}, editor = {Natal Jorge, Renato}, publisher = {CRC Press}, address = {Boca Raton}, isbn = {978-1-138-02910-1}, pages = {185 -- 188}, year = {2016}, language = {en} } @inproceedings{DuongJungFrotscheretal.2016, author = {Duong, Minh Tuan and Jung, Alexander and Frotscher, Ralf and Staat, Manfred}, title = {A 3D electromechanical FEM-based model for cardiac tissue}, series = {ECCOMAS Congress 2016, VII European Congress on Computational Methods in Applied Sciences and Engineering. Crete Island, Greece, 5-10 June 2016}, booktitle = {ECCOMAS Congress 2016, VII European Congress on Computational Methods in Applied Sciences and Engineering. Crete Island, Greece, 5-10 June 2016}, editor = {Papadrakakis, M.}, pages = {13 S.}, year = {2016}, language = {en} } @article{FrotscherMuanghongDursunetal.2016, author = {Frotscher, Ralf and Muanghong, Danita and Dursun, G{\"o}zde and Goßmann, Matthias and Temiz Artmann, Ayseg{\"u}l and Staat, Manfred}, title = {Sample-specific adaption of an improved electro-mechanical model of in vitro cardiac tissue}, series = {Journal of Biomechanics}, volume = {49}, journal = {Journal of Biomechanics}, number = {12}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0021-9290 (Print)}, doi = {10.1016/j.jbiomech.2016.01.039}, pages = {2428 -- 2435}, year = {2016}, abstract = {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.}, language = {en} } @article{GossmannFrotscherLinderetal.2016, author = {Goßmann, Matthias and Frotscher, Ralf and Linder, Peter and Bayer, Robin and Epple, U. and Staat, Manfred and Temiz Artmann, Ayseg{\"u}l and Artmann, Gerhard}, title = {Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells}, series = {Cellular physiology and biochemistry}, volume = {38}, journal = {Cellular physiology and biochemistry}, number = {3}, publisher = {Karger}, address = {Basel}, issn = {1421-9778 (Online)}, doi = {10.1159/000443124}, pages = {1182 -- 1198}, year = {2016}, abstract = {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.}, language = {en} }