Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan.
J Biomed Mater Res A. 2019 May;107(5):1080-1085. doi: 10.1002/jbm.a.36646. Epub 2019 Feb 19.
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.
体外肝细胞可能有助于治疗各种类型的肝脏疾病，但这些细胞会立即失去功能。在这里，我们设计了带有固定肝素结合表皮生长因子样生长因子 (HB-EGF) 的磺化聚轮烷 (PRX) 表面，以改善肝功能。磺化 PRX 三嵌段共聚物由磺丙基醚改性的 α-环糊精 (α-CDs) 组成，作为 PRX 段穿过聚乙二醇 (PEG) 链，PEG 两端的聚 (苄基甲基丙烯酸酯) 作为锚固段，通过滴涂法涂覆到聚苯乙烯表面上。具有少量穿线 α-CDs 的磺化 PRX 表面诱导 HepG2 细胞中 yes 相关蛋白的细胞质定位。此外，将 HB-EGF 固定到具有少量穿线 α-CDs 的磺化 PRX 表面上促进了肝功能，包括白蛋白分泌和基因表达。这些结果表明，调节 PRX 迁移性和固定生长因子的组合对于改善肝功能是有效的。© 2019 Wiley Periodicals, Inc. J 生物材料 Res 部分 A：107A：1080-1085，2019。
