Engineering molecularly mobile polyrotaxane surfaces with heparin-binding EGF-like growth factors for improving hepatocyte functions.

Abstract

Hepatocytes in vitro may be useful for treating various types of liver diseases, but these cells immediately lose their functions. Here, we designed sulfonated-polyrotaxane (PRX) surfaces with immobilized heparin binding-epidermal growth factor-like growth factors (HB-EGFs) for improving hepatic functions. Sulfonated-PRX triblock copolymers, composed of sulfopropyl ether-modified α-cyclodextrins (α-CDs) threaded onto a poly(ethylene glycol) (PEG) chain as a PRX segment and poly(benzyl methacrylate) at both terminals of the PEG as anchoring segments, were coated onto polystyrene surfaces by a drop cast method. The sulfonated-PRX surfaces with a small number of threading α-CDs induced cytoplasmic localization of yes-associated proteins in HepG2 cells. Moreover, immobilization of HB-EGFs onto the sulfonated-PRX surfaces with a small number of threading α-CDs promoted hepatic functions, including albumin secretion and gene expression. These results suggest that the combination of modulating the mobility of PRXs and immobilizing growth factors is effective for improving hepatic functions. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1080-1085, 2019.