000132434 001__ 132434
000132434 005__ 20240311111224.0
000132434 0247_ $$2doi$$a10.1016/j.compbiomed.2024.108044
000132434 0248_ $$2sideral$$a137641
000132434 037__ $$aART-2024-137641
000132434 041__ $$aeng
000132434 100__ $$aRosales, Ricardo M.
000132434 245__ $$aExperimentally-guided in silico design of engineered heart tissues to improve cardiac electrical function after myocardial infarction
000132434 260__ $$c2024
000132434 5060_ $$aAccess copy available to the general public$$fUnrestricted
000132434 5203_ $$aEngineered 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.
000132434 536__ $$9info:eu-repo/grantAgreement/ES/DGA/LMP94_21$$9info:eu-repo/grantAgreement/ES/DGA/T39-23R$$9info:eu-repo/grantAgreement/EUR/ERC-2014-StG-638284$$9info: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$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 874827-BRAV3$$9info:eu-repo/grantAgreement/ES/MCIN/PLEC2021-008127$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105674RB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-140556OB-I00$$9info:eu-repo/grantAgreement/EUR/MICINN/TED2021-130459B-I00
000132434 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000132434 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000132434 700__ $$0(orcid)0000-0003-2946-3044$$aMountris, Konstantinos A.
000132434 700__ $$0(orcid)0000-0001-5348-924X$$aOliván-Viguera, Aida
000132434 700__ $$0(orcid)0000-0002-3194-7796$$aPérez-Zabalza, María
000132434 700__ $$aCedillo-Servin, Gerardo
000132434 700__ $$aIglesias-García, Olalla
000132434 700__ $$aHrynevich, Andrei
000132434 700__ $$aCastilho, Miguel
000132434 700__ $$aMalda, Jos
000132434 700__ $$aPrósper, Felipe
000132434 700__ $$0(orcid)0000-0001-8741-6452$$aDoblaré, Manuel$$uUniversidad de Zaragoza
000132434 700__ $$aMazo, Manuel M.
000132434 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, Esther$$uUniversidad de Zaragoza
000132434 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000132434 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000132434 773__ $$g171 (2024), 108044 [13 pp.]$$pComput. biol. med.$$tComputers in biology and medicine$$x0010-4825
000132434 8564_ $$s3985817$$uhttps://zaguan.unizar.es/record/132434/files/texto_completo.pdf$$yVersión publicada
000132434 8564_ $$s2556422$$uhttps://zaguan.unizar.es/record/132434/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000132434 909CO $$ooai:zaguan.unizar.es:132434$$particulos$$pdriver
000132434 951__ $$a2024-03-11-09:51:08
000132434 980__ $$aARTICLE