Complexation of Hyaluronic Acid with Peptide-Based Supramolecular Hydrogel: Kinetic Pathway Dictates Electrostatic Complex Properties

Medulloblastoma (MB), the most common malignant brain tumor in children, originates in the cerebellum. Developing three-dimensional (3D) culture systems that mimic the brain extracellular matrix (ECM) is crucial for advancing drug discovery and MB treatment strategies. The MAX series of β-hairpin peptides can self-assemble into nanofibrillar hydrogels under physiological conditions, exhibiting shear-thinning and self-healing behavior. In this study, we employ the RGDS-MAX8 peptide hydrogel as a 3D culture platform to mimic the brain ECM. The incorporation of the RGDS at the N-terminus provides cell-adhesive sites to support cell-matrix interactions. Because the brain ECM contains a high concentration of hyaluronic acid (HA), we are developing various methods to incorporate HA at different concentrations within RGDS-MAX8 networks. The mechanical properties, including stiffness, shear-thinning, and recovery, are characterized by rheometry, while the nano- and microscale structures are examined by transmission electron microscopy and confocal microscopy. Specific pathways are required to both produce HA (negatively charged) and RGDS-MAX8 (positively charged) complexes and to retain desired hydrogel morphology and material properties.