Designing Dynamic Hydrogels: The Interplay of Cross-Linker Length, Valency, and Reaction Kinetics in Hydrazone-Based Networks

Hydrogels designed using dynamic (reversible) chemistry are prominent tools in diverse research areas as they grant access to time-dependent mechanical properties (self-healing and viscoelasticity), which are inaccessible via purely covalent networks. While the relationship between rate and equilibrium constants (RECs) and bulk mechanical properties is increasingly explored, less known is the effect of network topology or cross-linker length on both REC's and mechanical properties in dynamically cross-linked hydrogels. Here, we chose hydrazone formation as a model system for dynamic covalent network formation. Using mono- and bivalent hydrazides with molecular weights of 0.1-20 kg·mol^-1, we show that their chemical reactivity with a small molecule aldehyde is largely unaffected by their length. However, the apparent reactivity between two polymeric macromers revealed a decade reduction in <i>k</i> ₁ and <i>K</i> _eq compared with the model system. We then studied the impact of different cross-linkers on hydrogel mechanics, revealing a reduction in <i>G</i>' of 1.3-2.5-fold (cross-linker length) vs 18-28-fold (cross-linker valency), along with emergent strain-stiffening behavior. Finally, we offer potential mechanisms for these observations. These results present a step forward for the rational design of dynamic hydrogel systems with targeted mechanical properties, particularly by facilitating the translation of model studies to practical (macromeric) applications.