AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.2247
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RESEARCH ARTICLE

3D bioartificial stretchable scaffolds mimicking the mechanical hallmarks of human cardiac fibrotic tissue

Mattia Spedicati1,2,3 ,  Francesca Tivano1,2,3 ,  Alice Zoso1,2,3 ,  Janira Bei1 ,  Mario Lavella4 ,  Irene Carmagnola1,2,3 ,  Valeria Chiono1,2,3*
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1 Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Turin, Italy
2 POLITO BioMedLab, Politecnico di Torino, Turin, Turin, Italy
3 Interuniversity Centre for the Promotion of the 3Rs Principles in Teaching and Research (Centro 3R), Pisa, Italy
4 Department of Management, Information and Production Engineering, University of Bergamo, Dalmine, Bergamo, Italy
IJB 2024, 10(3), 2247 https://doi.org/10.36922/ijb.2247
Submitted: 15 November 2023 | Accepted: 21 March 2024 | Published: 15 May 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Human cardiac fibrotic tissues are characterized by a higher stiffness relative to healthy cardiac tissues. These tissues are unable to spontaneously contract and are subjected to passive mechanical stimulation during heart functionality. Moreover, scaffolds that can recapitulate the in vivo mechanical properties of the cardiac fibrotic tissues are lacking. Herein, this study aimed to design and fabricate mechanically stretchable bioartificial scaffolds with biomimetic composition and stiffness comparable to human cardiac fibrotic tissues. Poly(ε-caprolactone) (PCL) scaffolds with a stretchable mesh architecture were initially designed through structural and finite element method (FEM) analyses and subsequently fabricated by melt extrusion additive manufacturing (MEX). Scaffolds were surface functionalized by 3,4-dihydroxy-DL-phenylalanine (DOPA) polymerization (polyDOPA) to improve their interaction with natural polymers. Scaffold pores were then filled with different concentrations (5%, 7%, and 10% w/v) of gelatin methacryloyl (GelMA) hydrogels to support in vitro human cardiac fibroblasts (HCFs) 3D culture, thereby producing bioartificial PCL/GelMA scaffolds. Uniaxial tensile mechanical tests in static and dynamic conditions (1 Hz; 22% maximum strain) demonstrated that the bioartificial scaffolds had in vivo-like stretchability and similar stiffness to that of pathological cardiac tissue (tailored as a function of the number of PCL scaffold layers and GelMA hydrogel concentration). In vitro cell tests on bioartificial scaffolds using HCF-embedded GelMA hydrogels under static conditions displayed increasing cell viability, spreading, and cytoskeleton organization with decreasing GelMA hydrogel concentration. Moreover, α-smooth muscle actin (α-SMA)-positive cells were detected after 7 days of culture in static conditions followed by another 7 days of culture in dynamic conditions and not in HCF-loaded scaffolds cultured in static conditions for 14 days. These results suggested that in vitro culture under cyclic mechanical stimulations could induce an HCF phenotypic switch into myofibroblasts.

Keywords
Bioartificial scaffold
Cardiac fibrosis
Stretchable scaffold
GelMA hydrogel
Funding
This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation funding program (BIORECAR; Grant Agreement No. 772168).
Conflict of interest
The authors declare no conflicts of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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