Fabrication of functional liver tissues by cell sheet-based bioassembler technologies

Hepatocyte-based tissue engineering is an attractive method for the treatment of liver diseases. However, hepatocytes rapidly lose their viability and phenotypic functions on isolation from the native in vivo microenvironment of the liver. To overcome these problems, our laboratory has designed new types of thermoresponsive cell culture surfaces for advancing the next stage of cell sheet-based tissue engineering. One approach is to resemble the microstructures of native tissues and organs. Most in vivo tissues and organs have their own unique structures, such as multi-cellular, micrometer-scale organizations. Micropatterned thermoresponsive surfaces were designed to enable both the culturing and recovery of patterned heterotypic cell sheets. Another approach is to use extracellular matrices (ECMs), which resemble the surrounding environments of in vivo native tissues. Heparin-functionalized poly(N-isopropylacrylamide) (PIPAAm)-grafted cell culture surface, which interacts with heparin-binding proteins such as heparin-binding EGF-like growth factor (HB-EGF), has been designed for maintaining hepatic functions during the cultivation. The function of hepatic cell sheet was maintained by using these new types of thermoresponsive cell culture surfaces.