Shear and Compressive Stiffening of Dual-Cross-Linked Alginate Hydrogels with Tunable Viscoelasticity

Alginate biopolymers were modified with norbornene (Nb) and tetrazine (Tz) functional groups to generate hydrogel networks with tunable ionic and covalent cross-linking for modeling the strain-stiffening behavior of extracellular matrix. The mechanical properties of the hydrogels were investigated by oscillatory shear rheology, axial compression, and stress relaxation analysis. Introducing Nb-Tz irreversible covalent cross-links yielded dual-cross-linked hydrogels with stiffer and more elastic properties compared to purely ionically cross-linked alginate networks. The strain stiffening effect was observed under both shear amplitude sweeps and stepwise axial compression tests for the dual-cross-linked hydrogels. This study provides valuable insights into the structure-property relationship of dual-cross-linked biopolymer hydrogels for designing tunable extracellular matrix mimics of fibrotic tissues.