Abstract

Generating Models of Human Liver by 3D Bioprinting

William G Whitford, Strategic Solutions Leader, GE Healthcare Life Sciences

Decellularized extracellular matrix (ECM) represents an ideal source of the high water-content scaffold component of a bioink because it retains the biomimetic structural and biochemical features of the native liver ECM. In this study, we evaluate the bioprintability of human liver ECM under physiological conditions to assess the in vitro biocompatibility with human hepatic cells and to model liver fibrosis in vitro. Human hepatic cell lines (HepG2 and LX2) were gently mixed with HEP X™ bioink using a CELLMIXER^® directly into a cartridge before bioprinting. Tissue printing was performed in a BIO X 3D printer under physiological conditions. Bioprinted tissues were maintained in 3D culture up to 14 days and exposed to TGFß1 for 6 days in order to promote an in vitro fibrogenic process. The resultant bioprinted liver tissue was analysed by viability assay, histology and gene and protein expression. HepG2-laden constructs showed spontaneous formation of spheroids after 14 days in culture with up-regulation of albumin gene expression and protein secretion after 14 days compared to 7 days (p<0.001). To our knowledge, this is the first report describing the bioprinting of human hepatic tissue using human liver ECM as bioink.