Biologically-Inspired Melt Electrowriting for the Generationof Highly Biomimetic Functional Myocardium

Iglesias-García, Olalla ; Flandes-Iparraguirre, María ; Montero-Calle, Pilar ; Rosales, Ricardo M. ; Ullate-Agote, Asier ; Sánchez-Bueno, Andrea ; Larequi, Eduardo ; Anaut-Lusar, Ilazki ; Laita, Nicolás ; Oliván-Viguera, Aida ; Iglesias, Elena ; Abizanda, Gloria ; San Martín-Úriz, Patxi ; Aguirre-Ruiz, Paula ; Aranguren, Xabier L. ; García de Yébenes, Manuel ; Gavira, Juan José ; Martínez, Miguel Ángel ; Peña, Estefanía (Universidad de Zaragoza) ; Doblaré, Manuel (Universidad de Zaragoza) ; de-Juan-Pardo, Elena M. ; Pueyo, Esther (Universidad de Zaragoza) ; Prosper, Felipe ; Mazo Vega, Manuel M.

Resumen: 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.

Idioma: Inglés

DOI: 10.1002/adfm.202420106

Año: 2025

Publicado en: Advanced Functional Materials (2025), 2420106 [20 pp.]
ISSN: 1616-301X

Financiación: info:eu-repo/grantAgreement/ES/DGA/T39-23R
Financiación: 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
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CD22-00027
Financiación: info:eu-repo/grantAgreement/ES/MCIN/INVESTTRA_PID2022-142807OA-I00
Financiación: info:eu-repo/grantAgreement/ES/MCIN/PLEC2021-008127
Financiación: info:eu-repo/grantAgreement/ES/MCIN/VOLVAD_PID2022-142562OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2022-140556OB-I00
Financiación: info:eu-repo/grantAgreement/EUR/MICINN/TED2021-130459B-I00

Tipo y forma: Article (Published version)

Área (Departamento): Área Teoría Señal y Comunicac. (Dpto. Ingeniería Electrón.Com.)
Área (Departamento): Área Mec.Med.Cont. y Teor.Est. (Dpto. Ingeniería Mecánica)