The Influence of Crosslinker Architecture on Dynamic Covalent Hydrogel Viscoelasticity.

Dynamic covalent crosslinked (DCC) hydrogels represent a significant advance in biomaterials for regenerative medicine and mechanobiology. These gels typically offer viscoelasticity and self-healing properties that more closely mimic in vivo tissue mechanics than traditional, predominantly elastic, covalent crosslinked hydrogels. Despite their promise, the effects of varying crosslinker architecture - side chain versus telechelic crosslinks - on the viscoelastic properties of DCC hydrogels have not been thoroughly investigated. This study introduces hydrazone-based alginate hydrogels and examines how side-chain and telechelic crosslinker architectures impact hydrogel viscoelasticity and stiffness. In side-chain crosslinked gels, higher polymer concentrations, enhances stiffness and decelerates stress relaxation, while an off-stoichiometric hydrazine-to-aldehyde ratio leads to reduced stiffness and shorter relaxation time. In telechelic crosslinked gels, maximal stiffness and stress relaxation occurs at intermediate crosslinker concentrations for both linear and star crosslinkers, with higher crosslinker valency further increasing stiffness and decreasing relaxation rates. Our result suggested different ranges of stiffness and stress relaxation are accessible with the different crosslinker architectures, with side-chain crosslinking leading to gels with slower stress relaxation times relative to the other architectures, and star crosslinked gels providing increased stiffness and slower stress relaxation relative to linear crosslinked gels. The mechanical properties of hydrogels with star crosslinking are more robust to changes induced by competing chemical reactions compared to linear crosslinking. Our research underscores the pivotal role of crosslinker architecture in defining hydrogel stiffness and viscoelasticity, providing crucial insights for the design of DCC hydrogels with tailored mechanical properties for specific biomedical applications.