Construction of a Linear Cell Cross-Linker with Multivalent Glycyrrhetinic Acid Ligands for Rapid Formation of Hepatocyte Spheroids

Yang, MY (Yang, Meiyao)^[ 1 ] ; Li, YY (Li, Yingying)^[ 1 ] ; Wang, W (Wang, Wei)^[ 1 ] ; Yuan, Z (Yuan, Zhi)^[ 1,2 ] ; Li, Y (Li, Yu)^[ 1 ]

ACS BIOMATERIALS SCIENCE & ENGINEERING, 2018, 4(10): 3570-3577

DOI: 10.1021/acsbiomaterials.8b01036

 WOS:000447118600012

Abstract

We report herein the development of a novel cellular cross-linker further employed in the construction o(f) hepatocellular spheroids based on multivalent strategy. The linker structure consists of a glycyrrhetinic acid derivative (GA-N(CH3)(2)) modified alginate (ALG). GA-N(CH3)(2) is selected as the recognition ligand due to its high affinity toward hepatocyte, whereas ALG represents the linear backbone accounting for its good biocompatibility and flexible structure. These features endow the cellular cross-linker with the ability to flexibly interact with the cell through multiple binding sites, providing superior binding force between the cell and cross-linker, and subsequently rapidly combining multiple cells into cellular spheroids.