Recent advances of three-dimensional bioprinting technology in hepato-pancreato-biliary cancer models

Hepato-pancreato-biliary (HPB) cancer is a serious category of cancer including tumors originating in the liver, pancreas, gallbladder and biliary ducts. It is limited by two-dimensional (2D) cell culture models for studying its complicated tumor microenvironment including diverse contents and dynamic nature. Recently developed three-dimensional (3D) bioprinting is a state-of-the-art technology for fabrication of biological constructs through layer-by-layer deposition of bioinks in a spatially defined manner, which is computer-aided and designed to generate viable 3D constructs. 3D bioprinting has the potential to more closely recapitulate the tumor microenvironment, dynamic and complex cell-cell and cell-matrix interactions compared to the current methods, which benefits from its precise definition of positioning of various cell types and perfusing network in a high-throughput manner. In this review, we introduce and compare multiple types of 3D bioprinting methodologies for HPB cancer and other digestive tumors. We discuss the progress and application of 3D bioprinting in HPB and gastrointestinal cancers, focusing on tumor model manufacturing. We also highlight the current challenges regarding clinical translation of 3D bioprinting and bioinks in the field of digestive tumor research. Finally, we suggest valuable perspectives for this advanced technology, including combination of 3D bioprinting with microfluidics and application of 3D bioprinting in the field of tumor immunology.