Biologically‐Inspired Melt Electrowriting for the Generation of Highly Biomimetic Functional Myocardium
Year: 2025
Type: article
Abstract: In the heart, the specific 3D structure of myocardial layers produces an efficient ejection of blood. When myocardial infarction strikes, this architecture is disrupted, adding a disarranged contraction to the decreased availability of pumping units (cardiomyocytes, CMs). In this work, the alignment of cardiac fibers in a large animal model (pig) is characterized and employ melt electrowriting (MEW) to fabricate a bio‐inspired scaffold with diamond‐shaped pores. Using human‐induced pluripotent stem cell‐derived CMs and cardiac fibroblasts, human cardiac tissues with a biomimetic in‐plane contraction are generated. MEW‐diamond tissues beat macroscopically for over 1 month, with significantly faster kinetics, increased force, and higher conduction velocity than those based on square or rectangular pores. The diamond design induces a specific hiPSC‐CM alignment resulting in the observed in‐plane contraction. Transcriptomic analysis using bulk RNA‐seq reveals diamond‐MEW tissues present features of maturation as compared to traditional 2D cultures. Finally, the bio‐inspired cardiac tissues are employed to treat an infarction model in athymic rats, showing a significant benefit on systolic function and remodeling, tied to the presence of large grafts of human cells remuscularizing the ventricular wall. All in all, it is demonstrated that the new design generates superior human cardiac tissues with therapeutic capacity.
Source: Advanced Functional Materials
Authors: Olalla Iglesias‐García, María Flandes‐Iparraguirre, Pilar Montero‐Calle, Ricardo M. Rosales, Asier Ullate‐Agote, Andrea Sánchez‐Bueno, Eduardo Larequi, Ilazki Anaut‐Lusar, Nicolás Laita, Aida Oliván‐Viguera, Elena Iglesias, Gloria Abizanda, Patxi San Martín‐Úriz, Paula Aguirre‐Ruiz, Xabier L. Aranguren, Manuel García de Yébenes, Juan José Gavira, Miguel Ángel Martínez, Estefanía Peña, Manuel Doblaré, Elena M. de‐Juan‐Pardo, Esther Pueyo, Felipe Prosper, Manuel M. Mazo Vega
Institutions: Navarre Institute of Health Research, Centro de Investigación Médica Aplicada, Universidad de Zaragoza, Instituto de Investigación en Ingeniería de Aragón, Clinica Universidad de Navarra, Universidad de Navarra, Nanjing Tech University, Instituto de Investigación Sanitaria Aragón, The University of Western Australia, Harry Perkins Institute of Medical Research, Queen Elizabeth II Medical Centre, Centro de Investigación Biomédica en Red de Cáncer
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
Awards: G1105844351, G1175115578, G2262748287, BSICoS - Biomedical Signal Interpretation and Computational Simulation, G24120701, G2454037252, Computational biomechanics and bioengineering 3D printing to develop a personalized regenerative biological ventricular assist device to provide lasting functional support to damaged hearts, G2601397997, G294895050, G300979063, G3462379422, G3480869486, G3681454997, G4042783231, G4212894969, G425668148, G4937468798, G5038454122, G507957923, G5080475149, G538093817, G5635532810, G5774877837, G593054264, G5980248184, G6246066197, G6595330049, G683931746, G7127228594, G7169023097, G7805626310, G7863371703, G8164255987, G8492850202, G8497050386
OpenAlex ID: W4410779882