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

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, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
4 World-Class Research Center "Digital 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 3D bioprinting, mainly because they are recapitulating the native tissue microenvironment and retain key growth factors and cytokines. Hence, they are characterized by adequate biocompatibility for the use in 3D bioprinting. Regarding liver tissue engineering, these particular materials together with liver-derived cell types can serve as appropriate in vitro hepatic models, as well as models for drug efficiency testing and liver metabolism studies. These hydrogels can also be considered as GMP-compliant systems for liver cell and organoid expansion, in contrast to routinely used basal membrane extract products derived from tumorogenic cell lines. Although weak mechanical properties, as well as poor printability are the main hindrances for the direct usage of dECM hydrogels as bionks, various modifications of dECM and of the bioprinting process are applied to overcome these problems. However, there are several complications regarding the scale-up and GLP – compliant manufacturing of these hydrogels. First, the manufacturing standards for dECM hydrogels are not well established. Second, the methods for obtaining these hydrogels are slightly varying and therefore have decreased reproducibility. Third, since these hydrogels are traditionally produced from animal tissue, the animal-to-animal variability, different harvesting conditions and the bioburden reduction need to be thoroughly considered. This review examines the essential properties of decellularized extracellular matrix (dECM) hydrogels for biomedical applications, focusing on biocompatibility, mechanical strength, and bioactivity. It discusses production methods, modifications for 3D bioprinting, and highlights case studies of dECM-based liver constructs. Additionally, it 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 under grant agreement № 075-15-2024-640 (Sechenov University).
Conflict of interest
The authors declare no conflict of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing