Scaling liver bioprinting: A guide for usage of the hepatic extracellular matrix as a bioink
Valentin A. Brumberg , Polina Yu. Bikmulina , Artem A. Pozdnyakov , Zahra Heydari , Darya R. Zimulkina , Olga A. Smirnova , Frederico David Alencar de Sena Pereira , Anastasiia M. Nesterova , Svetlana L. Kotova , Massoud Vosough , Anastasia I. Shpichka , Peter S. Timashev
International Journal of Bioprinting ›› 2025, Vol. 11 ›› Issue (1) : 57 -83.
Scaling liver bioprinting: A guide for usage of the hepatic extracellular matrix as a bioink
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.
Bioprinting / Decellularized extracellular matrix / Hydrogels / Liver biofabrication / Crosslinking / Photopolymerization / Large-scale manufacturing
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