Influence of the physico-chemical bioink composition on the printability and cell biological properties in 3D-bioprinting of a liver tumor cell line

The selection of a suitable matrix material is crucial for the development of functional, biomimetic tissue and organ models. When these tissue models are fabricated with 3D-bioprinting technology, the requirements do not only include the biological functionality and physico-chemical properties, but also the printability. In our work, we therefore present a detailed study of seven different bioinks with the focus on a functional liver carcinoma model. Agarose, gelatin, collagen and their blends were selected as materials based on their benefits for 3D cell culture and Drop-on-Demand (DoD) bioprinting. The formulations were characterized for their mechanical (G' of 10-350 Pa) and rheological (viscosity 2-200 Pa*s) properties as well as albumin diffusivity (8-50 mu m(2)/s). The cellular behavior was exemplarily shown for HepG2 cells by monitoring viability, proliferation and morphology over 14 days, while the printability on a microvalve DoD printer was evaluated by drop volume monitoring in flight (100-250 nl), camera imaging of the wetting behavior and microscopy of the effective drop diameter (700 mu m and more). We did not observe negative effects on cell viability or proliferation, which is due to the very low shear stresses inside the nozzle (200-500 Pa). With our method, we could identify the strengths and weaknesses of each material, resulting in a material portfolio. By specifically selecting certain materials or blends, cell migration and possible interaction with other cells can be directed as indicated by the results of our cellular experiments.