Page 476 - IJB-10-3

International

Journal of Bioprinting

RESEARCH ARTICLE
3D bioartificial stretchable scaffolds mimicking

the mechanical hallmarks of human cardiac
fibrotic tissue

Mattia Spedicati 1,2,3† , Francesca Tivano 1,2,3† , Alice Zoso 1,2,3 , Janira Bei , Mario
1
Lavella , Irene Carmagnola 1,2,3 , and Valeria Chiono 1,2,3 *
4
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

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
† These authors contributed equally stiffness comparable to human cardiac fibrotic tissues. Poly(ε-caprolactone) (PCL)
to this work.
scaffolds with a stretchable mesh architecture were initially designed through
*Corresponding author: structural and finite element method (FEM) analyses and subsequently fabricated by
Valeria Chiono
(valeria.chiono@polito.it) melt extrusion additive manufacturing (MEX). Scaffolds were surface functionalized
by 3,4-dihydroxy-DL-phenylalanine (DOPA) polymerization (polyDOPA) to improve
Citation: Spedicati M, Tivano
F, Zoso A, et al. 3D bioartificial their interaction with natural polymers. Scaffold pores were then filled with different
stretchable scaffolds mimicking the concentrations (5%, 7%, and 10% w/v) of gelatin methacryloyl (GelMA) hydrogels
mechanical hallmarks of human to support in vitro human cardiac fibroblasts (HCFs) 3D culture, thereby producing
cardiac fibrotic tissue.
Int J Bioprint. 2024;10(3):2247. bioartificial PCL/GelMA scaffolds. Uniaxial tensile mechanical tests in static and
doi: 10.36922/ijb.2247 dynamic conditions (1 Hz; 22% maximum strain) demonstrated that the bioartificial
scaffolds had in vivo-like stretchability and similar stiffness to that of pathological
Received: November 15, 2023
Accepted: March 21, 2024 cardiac tissue (tailored as a function of the number of PCL scaffold layers and
Published Online: May 15, 2024 GelMA hydrogel concentration). In vitro cell tests on bioartificial scaffolds using
Copyright: © 2024 Author(s). HCF-embedded GelMA hydrogels under static conditions displayed increasing cell
This is an Open Access article viability, spreading, and cytoskeleton organization with decreasing GelMA hydrogel
distributed under the terms of the concentration. Moreover, α-smooth muscle actin (α-SMA)-positive cells were detected
Creative Commons Attribution
License, permitting distribution, after 7 days of culture in static conditions followed by another 7 days of culture in
and reproduction in any medium, dynamic conditions and not in HCF-loaded scaffolds cultured in static conditions
provided the original work is for 14 days. These results suggested that in vitro culture under cyclic mechanical
properly cited.
stimulations could induce an HCF phenotypic switch into myofibroblasts.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in Keywords: Bioartificial scaffold; Cardiac fibrosis; Stretchable scaffold;
published maps and institutional
affiliations. GelMA hydrogel

Volume 10 Issue 3 (2024) 468 doi: 10.36922/ijb.2247