Liver tissue engineering: From implantable tissue to whole organ engineering.

The term "liver tissue engineering" summarizes one of the ultimate goals of modern biotechnology: the possibility of reproducing in total or in part the functions of the liver in order to treat acute or chronic liver disorders and, ultimately, create a fully functional organ to be transplanted or used as an extracorporeal device. All the technical approaches in the area of liver tissue engineering are based on allocating adult hepatocytes or stem cell-derived hepatocyte-like cells within a three-dimensional structure able to ensure their survival and to maintain their functional phenotype. The hosting structure can be a construct in which hepatocytes are embedded in alginate and/or gelatin or are seeded in a pre-arranged scaffold made with different types of biomaterials. According to a more advanced methodology termed three-dimensional bioprinting, hepatocytes are mixed with a bio-ink and the mixture is printed in different forms, such as tissue-like layers or spheroids. In the last decade, efforts to engineer a cell microenvironment recapitulating the dynamic native extracellular matrix have become increasingly successful, leading to the hope of satisfying the clinical demand for tissue (or organ) repair and replacement within a reasonable timeframe. Indeed, the preclinical work performed in recent years has shown promising results, and the advancement in the biotechnology of bioreactors, perfusion machines, and cell expansion systems associated with a better understanding of liver development and the extracellular matrix microenvironment will facilitate and expedite the translation to technical applications. ( 2018;2:131-141).