Physiological Buffer Selection Alters the Mechanics of Hydrogels with Hydrazone Cross-Links

Hydrogels are used for a wide range of biomedical applications. While mechanical characterization of hydrogels is frequently performed in isotonic saline, the chemical identity of these solutions may vary widely from the ionic environments encountered during their use. To explore this idea, we test the mechanical properties of a hydrogel cross-linked with dynamic covalent chemistry (DCC) in several physiologically relevant ionic solutions that mimic different biological conditions. Specifically, we evaluate rheological properties of a hydrazone-cross-linked hydrogel composed of recombinant, chemically modified hyaluronan and elastin-like protein (ELP). Our results show that the shear moduli and stress relaxation properties of DCC hydrogels can vary significantly in different ionic environments. We identify the thermoresponsive nature of ELP and changes in hydrazone bond kinetics as the primary reasons for the observed differences in mechanical properties. Taken together, this work elucidates mechanisms underpinning changes in hydrogel mechanics in different physiological solutions.