3D bioprinting of Gelatin-Alginate bioinks for biofabrication of in vitro liver sinusoid model

Abstract

In vitro liver models are pivotal in early drug development as they serve in assessing drug toxicity. Currently, most of the liver models include static cultures of liver derived cell spheroids. Mimicking dynamic conditions (similar to native liver – such as blood flow, glucose gradients etc.) in in vitro liver models would be essential for studying drug induced liver injury (DILI). The current work investigated and developed a simple bioink composed of gelatin and alginate blends (GA) that can be used to 3D bioprint hepatocyte laden scaffolds, serving as an in vitro liver model for drug toxicity assays.Rheological evaluation (using a rotary rheometer) of various compositions of GA blends was performed to assess their printability with an extrusion bioprinter. Suitable GA compositions with human liver carcinoma cells (HepG2) were 3D bioprinted. The scaffolds were stabilized by crosslinking the alginate (using calcium chloride) and gelatin (using microbial transglutaminase). Cell viability and proliferation of HepG2 in bioprinted scaffolds was assessed for 28 days. Further work includes fabrication of HepG2 laden hollow tubes and colonization of inner lumen with human umbilical vein endothelial cells (HUVEC), followed by DILI studies in long-term perfusion culture.