Two synthetic supramolecular hydrogels, formed from bis-urea
amphiphiles
containing lactobionic acid (LBA) and maltobionic acid (MBA) bioactive
ligands, are applied as cell culture matricesin vitro. Their fibrillary and dynamic nature mimics essential features of
the extracellular matrix (ECM). The carbohydrate amphiphiles self-assemble
into long supramolecular fibers in water, and hydrogels are formed
by physical entanglement of fibers through bundling. Gels of both
amphiphiles exhibit good self-healing behavior, but remarkably different
stiffnesses. They display excellent bioactive properties in hepatic
cell cultures. Both carbohydrate ligands used are proposed to bind
to asialoglycoprotein receptors (ASGPRs) in hepatic cells, thus inducing
spheroid formation when seeding hepatic HepG2 cells on both supramolecular
hydrogels. Ligand nature, ligand density, and hydrogel stiffness influence
cell migration and spheroid size and number. The results illustrate
the potential of self-assembled, carbohydrate-functionalized hydrogels
as matrices for liver tissue engineering.