Hepatic Spheroid Formation on Carbohydrate-Functionalized Supramolecular Hydrogels

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Supramolecular Chemistry

Background:

• The extracellular matrix (ECM) is crucial for cell function and tissue development.
• Mimicking ECM properties with synthetic materials is key for regenerative medicine.
• Hepatic cell culture requires specialized matrices to maintain function and promote tissue formation.

Purpose of the Study:

• To develop and characterize synthetic supramolecular hydrogels for liver tissue engineering.
• To investigate the bioactivity and cell-matrix interactions of carbohydrate-functionalized hydrogels.
• To assess the potential of these hydrogels in promoting hepatic cell spheroid formation and migration.

Main Methods:

• Synthesis of bis-urea amphiphiles with lactobionic acid (LBA) and maltobionic acid (MBA) ligands.
• Characterization of hydrogel self-assembly, fibrillary structure, and mechanical properties (stiffness, self-healing).
• In vitro evaluation of hydrogel bioactivity using hepatic HepG2 cell cultures, including spheroid formation and cell migration assays.

Main Results:

• Carbohydrate amphiphiles self-assembled into supramolecular fibers, forming physically entangled hydrogels.
• Hydrogels exhibited good self-healing properties but varied significantly in stiffness.
• Both LBA- and MBA-functionalized hydrogels demonstrated excellent bioactivity, inducing hepatic cell spheroid formation via ASGPR binding.
• Ligand characteristics and hydrogel stiffness influenced cell migration, spheroid size, and number.

Conclusions:

• Self-assembled, carbohydrate-functionalized hydrogels show promise as advanced cell culture matrices.
• These hydrogels effectively mimic ECM features and support hepatic cell functions, including spheroid formation.
• The study highlights the potential of these dynamic biomaterials for liver tissue engineering applications.