Development of Liver Decellularized Extracellular Matrix Bioink for Three-Dimensional Cell Printing-Based Liver Tissue Engineering

TLDR

The liver is essential for human physiology, yet donor shortages and drug‑induced injury drive the search for alternative in‑vitro models, and 3D cell printing offers a promising approach that requires optimized biomaterials. This study aimed to develop and characterize a liver decellularized extracellular matrix (dECM) bioink for 3D cell printing. The authors formulated the dECM bioink, optimized printing parameters, and assessed its printability and fidelity for 3D cell printing. The dECM bioink preserved liver ECM components, removed cellular material, exhibited suitable printability, promoted stem cell differentiation, enhanced HepG2 function, and is a promising candidate for liver tissue engineering.

Abstract

The liver is an important organ and plays major roles in the human body. Because of the lack of liver donors after liver failure and drug-induced liver injury, much research has focused on developing liver alternatives and liver in vitro models for transplantation and drug screening. Although numerous studies have been conducted, these systems cannot faithfully mimic the complexity of the liver. Recently, three-dimensional (3D) cell printing technology has emerged as one of a number of innovative technologies that may help to overcome this limitation. However, a great deal of work in developing biomaterials optimized for 3D cell printing-based liver tissue engineering remains. Therefore, in this work, we developed a liver decellularized extracellular matrix (dECM) bioink for 3D cell printing applications and evaluated its characteristics. The liver dECM bioink retained the major ECM components of the liver while cellular components were effectively removed and further exhibited suitable and adjustable properties for 3D cell printing. We further studied printing parameters with the liver dECM bioink to verify the versatility and fidelity of the printing process. Stem cell differentiation and HepG2 cell functions in the liver dECM bioink in comparison to those of commercial collagen bioink were also evaluated, and the liver dECM bioink was found to induce stem cell differentiation and enhance HepG2 cell function. Consequently, the results demonstrate that the proposed liver dECM bioink is a promising bioink candidate for 3D cell printing-based liver tissue engineering.