A study on extracellular and cellular composition to advance towards the rational design of contractile human myocardium
Year: 2026
Type: article
Abstract: The recapitulation of the physiological cellular composition, 3D structure and mechanics of the human myocardium is key to improving the biofabrication of cardiac tissues. To advance the development of engineered heart patches, with significant potential for human cardiac repair, we assessed the impact of their cellular and extracellular constituents on tissue organization and function, by using advanced biofabrication and next-generation sequencing technologies. Combining melt electrowriting (MEW) fibrillary scaffolds with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) and cardiac fibroblasts (-CFs), we generated human engineered cardiac tissues (MEW-hECTs) by casting in two different biomaterial compositions (fibrin and gelatin-methacryloyl (GelMA)), and varying proportions of the cardiac constituent cells. Under the conditions tested, fibrin-hECTs displayed improved tissue formation, coordinated contraction, structural organization, and electrophysiological behavior compared with GelMA-hECTs. Transcriptomics analysis indicated that fibrin-hECTs exhibited an increase in maturation-associated gene expression signatures compared with GelMA-hECTs, whereas a longer remodeling process of the synthetic environment was required in GelMA. Surprisingly, within the investigated MEW-based composite system, the inclusion of CFs had no positive impact on tissue organization and impaired the electrophysiological properties of myocardial constructs, increasing susceptibility to arrhythmias in computational simulations calibrated with experimental electrophysiological data. This information will help devise advanced myocardial tissues by enabling a comprehensive assessment of the main components, ultimately reflecting the unique native cardiac 3D organization.
Source: Materials Today Bio
Authors: Olalla Iglesias-García, Asier Ullate-Agote, Jiabin Qin, Aida Oliván-Viguera, Laura García-Mendívil, Gerardo Cedillo-Servin, Johannes Braig, Jose Valdés-Fernández, Inge Dokter, Ilazki Anaut-Lusar, Eduardo Larequi, Patxi San Martin-Uriz, Paula Aguirre-Ruiz, Pedro Vicente, Ricardo M. Rosales, Ana María Sánchez de la Nava, Ainitze Gereka Goienetxe, Ane Miren Zaldua, María Eugenia Fernández-Santos, Manuel García de Yébenes, Juan José Gavira, Miguel Castilho, Paula M. Alves, Margarida Serra, Ming Wu, Stefan Janssens, Tomasz Jüngst, Jürgen Groll, Jos Malda, Esther Pueyo, Manuel Doblaré, Joost P.G. Sluijter, Alain van Mil, Felipe Prósper, Manuel M. Mazo Vega
Institutions: Navarre Institute of Health Research, Centro de Investigación Médica Aplicada, Utrecht University, University Medical Center Utrecht, Universidad de Zaragoza, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Instituto de Investigación Sanitaria Aragón, Instituto de Investigación en Ingeniería de Aragón, Eindhoven University of Technology, University of Würzburg, Bavarian Polymer Institute, Instituto de Biologia Experimental e Tecnológica, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Hospital General Universitario Gregorio Marañón, Centro de Investigación en Red en Enfermedades Cardiovasculares, Instituto de Investigación Sanitaria Gregorio Marañón, Leartiker, Clinica Universidad de Navarra, KU Leuven, Universitair Ziekenhuis Leuven, Centro de Investigación Biomédica en Red de Cáncer
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,400
OpenAlex ID: W7208727572