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 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.