Fabrication of human myocardium using multidimensional modelling of engineered tissues.

Autor:	Montero-Calle P; Regenerative Medicine Program, Cima Universidad de Navarra, Pamplona, Spain., Flandes-Iparraguirre M; Regenerative Medicine Program, Cima Universidad de Navarra, Pamplona, Spain., Mountris K; Aragón Institute for Engineering Research (I3A) University of Zaragoza, Zaragoza, Spain.; Department of Mechanical Engineering, University College London, London, United Kingdom., S de la Nava A; Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain & CIBERCV, ISCIII, Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain., Laita N; Aragón Institute for Engineering Research (I3A) University of Zaragoza, Zaragoza, Spain., Rosales RM; Aragón Institute for Engineering Research (I3A) University of Zaragoza, Zaragoza, Spain.; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain., Iglesias-García O; Regenerative Medicine Program, Cima Universidad de Navarra, Pamplona, Spain., de-Juan-Pardo EM; T3mPLATE, Harry Perkins Institute of Medical Research, QEII Medical Centre and UWA Centre for Medical Research, The University of Western Australia, Perth, Australia., Atienza F; Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain & CIBERCV, ISCIII, Madrid, Spain.; Universidad Complutense, Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain., Fernández-Santos ME; Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain & CIBERCV, ISCIII, Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain., Peña E; Aragón Institute for Engineering Research (I3A) University of Zaragoza, Zaragoza, Spain.; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain., Doblaré M; Aragón Institute for Engineering Research (I3A) University of Zaragoza, Zaragoza, Spain.; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain., Gavira JJ; Department of Cardiology, Clínica Universidad de Navarra, Pamplona, Spain.; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain., Fernández-Avilés F; Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain & CIBERCV, ISCIII, Madrid, Spain.; Universidad Complutense, Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain., Prósper F; Regenerative Medicine Program, Cima Universidad de Navarra, Pamplona, Spain.; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.; Hematology and Cell Therapy, Clínica Universidad de Navarra, Pamplona, Spain.; CIBER de Cáncer (CIBERONC, team CB16/12/00489), Pamplona, Spain., Pueyo E; Aragón Institute for Engineering Research (I3A) University of Zaragoza, Zaragoza, Spain.; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain., Mazo MM; Regenerative Medicine Program, Cima Universidad de Navarra, Pamplona, Spain.; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.; Hematology and Cell Therapy, Clínica Universidad de Navarra, Pamplona, Spain.
Jazyk:	angličtina
Zdroj:	Biofabrication [Biofabrication] 2022 Sep 14; Vol. 14 (4). Date of Electronic Publication: 2022 Sep 14.
DOI:	10.1088/1758-5090/ac8cb3
Abstrakt:	Biofabrication of human tissues has seen a meteoric growth triggered by recent technical advancements such as human induced pluripotent stem cells (hiPSCs) and additive manufacturing. However, generation of cardiac tissue is still hampered by lack of adequate mechanical properties and crucially by the often unpredictable post-fabrication evolution of biological components. In this study we employ melt electrowriting (MEW) and hiPSC-derived cardiac cells to generate fibre-reinforced human cardiac minitissues. These are thoroughly characterized in order to build computational models and simulations able to predict their post-fabrication evolution. Our results show that MEW-based human minitissues display advanced maturation 28 post-generation, with a significant increase in the expression of cardiac genes such as MYL2, GJA5, SCN5A and the MYH7/MYH6 and MYL2/MYL7 ratios. Human iPSC-cardiomyocytes are significantly more aligned within the MEW-based 3D tissues, as compared to conventional 2D controls, and also display greater expression of C × 43. These are also correlated with a more mature functionality in the form of faster conduction velocity. We used these data to develop simulations capable of accurately reproducing the experimental performance. In-depth gauging of the structural disposition (cellular alignment) and intercellular connectivity (C × 43) allowed us to develop an improved computational model able to predict the relationship between cardiac cell alignment and functional performance. This study lays down the path for advancing in the development of in silico tools to predict cardiac biofabricated tissue evolution after generation, and maps the route towards more accurate and biomimetic tissue manufacture. (Creative Commons Attribution license.)
Databáze:	MEDLINE
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