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

We report herein the development of a novel cellular cross-linker further employed in the construction of 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.