AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.4343
REVIEW

Scaling liver bioprinting: A guide for usage of the hepatic extracellular matrix as a bioink

Valentin A. Brumberg1 Polina Yu. Bikmulina1 Artem A. Pozdnyakov1 Zahra Heydari1 Darya R. Zimulkina1 Olga A. Smirnova1 Frederico David Alencar de Sena Pereira1 Anastasiia M. Nesterova1 Svetlana L. Kotova1 Massoud Vosough2,3 Anastasia I. Shpichka1 Peter S. Timashev1,4,5*
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1 Institute for Regenerative Medicine, Sechenov University, Moscow, Russia
2 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
3 Experimental Cancer Medicine Group, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
4 World-Class Research Center “Digital biodesign Biodesign and Personalized Healthcare”, Sechenov University, Moscow, Russia
5 Chemistry Department, Lomonosov Moscow State University, Moscow, Russia
Submitted: 26 July 2024 | Accepted: 26 September 2024 | Published: 26 September 2024
(This article belongs to the Special Issue Made-to-order Organ)
© 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/ )
Abstract

Hydrogels derived from the decellularized extracellular matrix (dECM) are widely used in three-dimensional (3D) bioprinting, mainly because they recapitulate the native tissue microenvironment and retain key growth factors and cytokines. Hence, they are characterized by adequate biocompatibility for use in 3D bioprinting. In liver tissue engineering, these materials, along with liver-derived cell types, can serve as appropriate in vitro hepatic models for drug efficiency testing and liver metabolism studies. These hydrogels can also be considered as good manufacturing practice-compliant systems for liver cell and organoid expansion, unlike routinely used basal membrane extract products derived from tumorigenic cell lines. Although weak mechanical properties and poor printability hinder the direct usage of dECM hydrogels as bioinks, various modifications of dECM and the bioprinting process are applied to overcome these problems. However, there are several complications regarding the scale-up and good laboratory practice-compliant manufacturing of these hydrogels: (i) the manufacturing standards for dECM hydrogels are not well established; (ii) the methods for obtaining these hydrogels are slightly varying, resulting in decreased reproducibility; and (iii) since these hydrogels are traditionally produced from animal tissue, the animal-to-animal variability, different harvesting conditions, and bioburden reduction need to be thoroughly considered. This review examines the essential properties of dECM hydrogels for biomedical applications, focusing on biocompatibility, mechanical strength, and bioactivity. Additionally, this review discusses production methods and modifications for 3D bioprinting, highlights case studies of dECM-based liver constructs, and addresses challenges in scalability and regulatory hurdles for clinical translation.

Keywords
Bioprinting
Decellularized extracellular matrix
Hydrogels
Liver biofabrication
Crosslinking
Photopolymerization
Large-scale manufacturing
Funding
The work was carried out with financial support from the Ministry of Science and Higher Education of the Russian Federation (grant agreement no. 075-15-2024-640; Sechenov University).
Conflict of interest
Peter S. Timashev serves as a guest editor for the journal but was not in any way (directly or indirectly) involved in the editorial and peer-review process conducted for this paper. The other authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing