AccScience Publishing / IJB / Volume 9 / Issue 5 / DOI: 10.18063/ijb.771

An integrated in silico–in vitro approach for bioprinting core–shell bioarchitectures

Nicole Guazzelli1,2,3† Ludovica Cacopardo1,2,3†* Alessandro Corti4 Arti Ahluwalia1,2,3
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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
Submitted: 4 March 2023 | Accepted: 2 May 2023 | Published: 12 June 2023
(This article belongs to the Special Issue 3D Bioprinting for Materials and Application)
© 2023 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 ( )

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 based on alginate. A finite element model is used to compute the hindered diffusion and crosslinking phenomena involved in the formation of core–shell structures and to predict the width of the shell as a function of material parameters. Constructs 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 were bioprinted respectively in a liquid core (10 mg/mL Pluronic) and in a solid shell (20 mg/mL alginate plus 20 mg/mL gelatin, used for providing the cells with adhesive moieties). These constructs had a roundness of 97.6% and an average diameter of 1500 ±136 μm. Moreover, their viability was close to monolayer controls (74.12% ± 22.07%) after a week in culture, and the paracellular transport was twice that of cellfree constructs, indicating cell polarization.

Core–shell spheroids
3D models
Biological barriers
In silico models

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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing