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Controlling the selective and directional migration of hepatocytes by a complementary density gradient of glycosylated hyperbranched polymers and poly(ethylene glycol) molecules

Year: 2017

Journal: Acta Biomater., Volume 56, JUL 1, page 161–170

Authors: Liang, Su; Yu, Shan; Zhou, Ning; Deng, Jun; Gao, Changyou

Keywords: Directional cell migration; Selective cell adhesion; Complementary gradient; Hepatocytes; Carbohydrate-protein interaction

Repair and regeneration of defected tissues and organs depends strongly on the directional migration of targeted cells, for example, the enhancement of directional migration of hepatocytes could be helpful in liver regeneration and transplantation. Herein a complementary gradient of galactose-modified hyperbranched polymers (LA-HPMA) and poly(ethylene glycol) (PEG) molecules was designed and prepared on a same substrate. Characterizations of X-ray photoelectron spectrometry and quartz crystal microbalance with dissipation (QCM-d) demonstrated the unidirectional change in grafting density of LA-HPMA and PEG molecules, respectively. On the LA-HPMA/PEG complementary gradient surface, the human hepatoma (HepG2) cells showed preferential orientation and enhanced directionalmigration toward the region of lower PEG density and higher LA-HPMA density. By contrast, the mouse embryonic fibroblasts (NIH3T3) showed random migration irrelevant to the gradient. The success of the complementary gradient relies on the specific interaction between galactose and asialoglycoprotein receptor (ASGPR) expressed on HepG2 cells. Statement of Significance A continuous complementary gradient of glycosylated hyperbranched polymers and PEG is fabricated to govern cell-substrate interaction. Selective and directional migration of hepatocytes over fibroblasts is achieved on the complementary gradient. A new perspective on designing complex biomaterials for desired tissue regeneration. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.