132434 20260217205458.0 doi 10.1016/j.compbiomed.2024.108044 sideral 137641 ART-2024-137641 eng Rosales, Ricardo M. Experimentally-guided in silico design of engineered heart tissues to improve cardiac electrical function after myocardial infarction 2024 Access copy available to the general public Unrestricted Engineered heart tissues (EHTs) built from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) showed promising results for cardiac function restoration following myocardial infarction. Nevertheless, human iPSC-CMs have longer action potential and lower cell-to-cell coupling than adult-like CMs. These immature electrophysiological properties favor arrhythmias due to the generation of electrophysiological gradients when hiPSC-CMs are injected in the cardiac tissue. Culturing hiPSC-CMs on three-dimensional (3D) scaffolds can promote their maturation and influence their alignment. However, it is still uncertain how on-scaffold culturing influences the overall electrophysiology of the in vitro and implanted EHTs, as it requires expensive and time consuming experimentation. Here, we computationally investigated the impact of the scaffold design on the EHT electrical depolarization and repolarization before and after engraftment on infarcted tissue. We first acquired and processed electrical recordings from in vitro EHTs, which we used to calibrate the modeling and simulation of in silico EHTs to replicate experimental outcomes. Next, we built in silico EHT models for a range of scaffold pore sizes, shapes (square, rectangular, auxetic, hexagonal) and thicknesses. In this setup, we found that scaffolds made of small (0.2 mm2), elongated (30° half-angle) hexagons led to faster EHT activation and better mimicked the cardiac anisotropy. The scaffold thickness had a marginal role on the not engrafted EHT electrophysiology. Moreover, EHT engraftment on infarcted tissue showed that the EHT conductivity should be at least 5% of that in healthy tissue for bidirectional EHT-myocardium electrical propagation. For conductivities above such threshold, the scaffold made of small elongated hexagons led to the lowest activation time (AT) in the coupled EHT-myocardium. If the EHT conductivity was further increased and the hiPSC-CMs were uniformly oriented parallel to the epicardial cells, the total AT and the repolarization time gradient decreased substantially, thus minimizing the likelihood for arrhythmias after EHT transplantation. info:eu-repo/grantAgreement/ES/DGA/LMP94_21 info:eu-repo/grantAgreement/ES/DGA/T39-23R info:eu-repo/grantAgreement/EUR/ERC-2014-StG-638284 info:eu-repo/grantAgreement/EC/H2020/874827/EU/Computational biomechanics and bioengineering 3D printing to develop a personalized regenerative biological ventricular assist device to provide lasting functional support to damaged hearts/BRAV3 This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 874827-BRAV3 info:eu-repo/grantAgreement/ES/MCIN/PLEC2021-008127 info:eu-repo/grantAgreement/ES/MICINN/PID2019-105674RB-I00 info:eu-repo/grantAgreement/ES/MICINN/PID2022-140556OB-I00 info:eu-repo/grantAgreement/EUR/MICINN/TED2021-130459B-I00 info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es 6.3 2024 BIOLOGY 7 / 107 = 0.065 2024 Q1 T1 MATHEMATICAL & COMPUTATIONAL BIOLOGY 4 / 67 = 0.06 2024 Q1 T1 ENGINEERING, BIOMEDICAL 22 / 124 = 0.177 2024 Q1 T1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS 26 / 177 = 0.147 2024 Q1 T1 1.447 2024 Health Informatics 2024 Q1 Computer Science Applications 2024 Q1 13.0 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Mountris, Konstantinos A. (orcid)0000-0003-2946-3044 Oliván-Viguera, Aida (orcid)0000-0001-5348-924X Pérez-Zabalza, María (orcid)0000-0002-3194-7796 Cedillo-Servin, Gerardo Iglesias-García, Olalla Hrynevich, Andrei Castilho, Miguel Malda, Jos Prósper, Felipe Doblaré, Manuel Universidad de Zaragoza (orcid)0000-0001-8741-6452 Mazo, Manuel M. Pueyo, Esther Universidad de Zaragoza (orcid)0000-0002-1960-407X 5008 800 Universidad de Zaragoza Dpto. Ingeniería Electrón.Com. Área Teoría Señal y Comunicac. 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 171 (2024), 108044 [13 pp.] Comput. biol. med. Computers in biology and medicine 0010-4825 3985817 http://zaguan.unizar.es/record/132434/files/texto_completo.pdf Versión publicada 2556422 http://zaguan.unizar.es/record/132434/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:132434 articulos driver 2026-02-17-20:21:08 ARTICLE