Liver dECM-Gelatin Composite Bioink for Precise 3D Printing of Highly Functional Liver Tissues

Abstract

In recent studies, liver decellularized extracellular matrix (dECM)-based bioinks have gained significant attention for their excellent compatibility with hepatocytes. However, their low printability limits the fabrication of highly functional liver tissue. In this study, a new liver dECM-gelatin composite bioink (dECM gBioink) was developed to overcome this limitation. The dECM gBioink was prepared by incorporating a viscous gelatin mixture into the liver dECM material. The novel dECM gBioink showed 2.44 and 10.71 times higher bioprinting resolution and compressive modulus, respectively, than a traditional dECM bioink. In addition, the new bioink enabled stable stacking with 20 or more layers, whereas a structure printed with the traditional dECM bioink collapsed. Moreover, the proposed dECM gBioink exhibited excellent hepatocyte and endothelial cell compatibility. At last, the liver lobule mimetic structure was successfully fabricated with a precisely patterned endothelial cell cord-like pattern and primary hepatocytes using the dECM gBioink. The fabricated lobule structure exhibited excellent hepatic functionalities and dose-dependent responses to hepatotoxic drugs. These results demonstrated that the gelatin mixture can significantly improve the printability and mechanical properties of the liver dECM materials while maintaining good cytocompatibility. This novel liver dECM gBioink with enhanced 3D printability and resolution can be used as an advanced tool for engineering highly functional liver tissues.