Page 441 - IJB-9-5

International Journal of Bioprinting

RESEARCH ARTICLE
An integrated in silico–in vitro approach for

bioprinting core–shell bioarchitectures

Nicole Guazzelli 1,2,3† , Ludovica Cacopardo 1,2,3† *, Alessandro Corti ,
4
Arti Ahluwalia 1,2,3
1 Department of Information Engineering, University of Pisa, Pisa, Italy
2 Research Center E. Piaggio, University of Pisa, Pisa, Italy
3 3R Centre, Inter-University Centre for the Promotion of the 3R Principles in Education and
Research, University of Pisa, Pisa, Italy
4 Department of Translational Research and New Technologies in Medicine and Surgery, University
of Pisa, Pisa, Italy
(This article belongs to the Special Issue: 3D Bioprinting for Materials and Application)

Abstract

Biological tissues possess a high degree of structural complexity characterized by
curvature and stratification of different tissue layers. Despite recent advances in
in vitro technology, current engineering solutions do not comprise both of these
features. In this paper, we present an integrated in silico–in vitro strategy for the design
and fabrication of biological barriers with controlled curvature and architecture.
Analytical and computational tools combined with advanced bioprinting methods
are employed to optimize living inks for bioprinting-structured core–shell constructs
† These authors contributed equally based on alginate. A finite element model is used to compute the hindered diffusion
to this work.
and crosslinking phenomena involved in the formation of core–shell structures and
*Corresponding author: to predict the width of the shell as a function of material parameters. Constructs
Ludovica Cacopardo
(ludovica.cacopardo@unipi.it) with a solid alginate-based shell and a solid, liquid, or air core can be reproducibly
printed using the workflow. As a proof of concept, epithelial cells and fibroblasts
Citation: Guazzelli N, were bioprinted respectively in a liquid core (10 mg/mL Pluronic) and in a solid shell
Cacopardo L, Corti A, et al., 2023,
An integrated in silico–in vitro (20 mg/mL alginate plus 20 mg/mL gelatin, used for providing the cells with adhesive
approach for bioprinting core–shell moieties). These constructs had a roundness of 97.6% and an average diameter of
bioarchitectures. Int J Bioprint, 1500 ±136 μm. Moreover, their viability was close to monolayer controls (74.12% ±
9(5): 771.
https://doi.org/10.18063/ijb.771 22.07%) after a week in culture, and the paracellular transport was twice that of cell-
free constructs, indicating cell polarization.
Received: March 4, 2023
Accepted: May 2, 2023
Published Online: June 12, 2023
Keywords: Core–shell spheroids; Bioprinting; 3D models; Curvotaxis; Biological
Copyright: © 2023 Author(s). barriers; In silico models
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium, 1. Introduction
provided the original work is
properly cited. Many organs possess a multilayer organization which derives from tissue primordia [1,2] .
Publisher’s Note: Whioce In vivo, the tissue layers form complex three-dimensional (3D) shapes which may often
Publishing remains neutral with be topologically represented by core–shell structures. Cell constructs with core–shell
regard to jurisdictional claims in
published maps and institutional geometries can be fabricated to recapitulate these architectures and are a fascinating
affiliations. research topic. They also provide a means of investigating cell organization in highly

Volume 9 Issue 5 (2023) 433 https://doi.org/10.18063/ijb.771