Internal Structure of Hyaluronic Acid Hydrogels Controlled by Iron(III) Ion-Catechol Complexation

This study explores the internal structure of catechol-functionalized hyaluronic acid (HA-CA) hydrogels with different types of Fe3+-induced cross-linking. We previously reported HA-CA hydrogels cross-linked by covalent catechol coupling and by Fe3+-catechol coordination bonds. Here, we determine the internal structures of these gels using electron paramagnetic resonance, small-angle X-ray scattering, and neutron scattering. Phase-controllable structures were observed in relation to certain pH conditions and gelation pathways. First, we examined the structures of HA-CA gels developed from covalently cross-linked prenetworks, which allow additional Fe3+-catechol coordination bonds of mono, bis, and tris complexes depending on the pH condition. Second, we investigated the structural aspects of the gels preserved by Fe3+-catechol tris complexes, developed from both cross-linked prenetworks and un-cross-linked polymer solutions. The results show that the characteristics of the chains govern the network structures due to the changes in oxidation state of the functional groups, carboxylic acid and catechol, in the given environments. We also discuss the structural aspects, i.e., microphase separation, additional cross-linking within the restricted prenetworks, and locally stretched polymer chains. The observations here suggest that various structural characteristics can be considered to assist a number of different applications using biopolymers.