Bioinspired Engineering for Liver Tissue Regeneration and Development of Bioartificial Liver: A Review

Patients with advanced liver disease have very high mortality due to associated complications such as hepatic encephalopathy, hepatorenal syndrome, and multiorgan failure. Liver transplant is the only therapeutic option for such patients; however, problems linked to availability, cost, complications, and side effects limit its practical application. The strong potential for hepatic regeneration and recovery has been documented in liver disease, without advance decomposition of the liver. Recently, hepatocyte transplantation was used as an alternative to liver transplantation, but insufficient numbers of functional hepatocytes for therapeutic efficacy limits its use. In addition, extracorporeal liver support systems are a modality for patient management or they can be used as a bridge to a possible liver transplant. But such systems lack clear-cut survival benefits, specifically in advanced liver disease. Due to the limited amount of organ donations and living donor liver transplantation across the globe, novel technologies have been proposed for development of three-dimensional (3D) composite constructs, 3D perfused bioreactors for spheroid culture, liver-on-chip platforms, and bioprinted liver to produce an implantable in vitro liver that can reliably predict in vivo-like tissue responses and suitability for drug toxicity testing. These research fields stand to be game changers in regeneration and repair of liver tissues in patients. This review focuses on novel technologies that are currently used for liver regeneration and production of transplantable liver.