Induction of liver proliferation using a polymeric platform in mice

Currently, animal models of liver regeneration are based on extensive lesions of the native organ and on cellular approaches using biomaterials to host growth factors and extracellular components to create artificial liver systems. We report a polymeric biological platform, minimally invasive, that induced sequential proliferation of liver parenchyma inside the scaffold in mice. Porous discs of polyether-polyurethane were surgically placed under the left liver lobe and removed at days 4, 8, 12 and 25 after implantation. No exogenous growth factors or extracellular matrix components were added to the scaffold. Histological analysis of the implants was performed to identify hepatocytes, liver vascular structures and bile ducts in the newly formed tissue. In addition, systemic markers for hepatic function were determined. This biohybrid device provided a scaffold that was gradually filled with parenchymal and non-parenchymal liver tissue as detected by histological analysis. At day 4, the pores of the scaffold were filled with inflammatory cells and spindled-shaped like fibroblasts, and extracellular matrix components. At day 8, hepatocytes clusters, central lobular hepatic veins, portal space containing arteries, veins and biliary ducts were detected. By days 12 and 25 a liver-like structure filled 2/3 of the scaffold. Its organization resembled that of a mature liver. Serum concentration of ALT increased three-fold initially after implantation, returning gradually to control levels. The plain synthetic scaffold (without addition of exogenous molecules) placed under the intact left liver lobe exhibits the potential to investigate physiological mechanisms that regulate liver parenchyma proliferation.