Tuning the Viscoelasticity of Supramolecular Alginate Hydrogels via Homoternary FGG–Peptide–Cucurbit[8]uril Complexes

Cell-ECM communication plays a critical role in the correct tissue development, disease progression, and therapeutic outcomes. The interest in controlling the mechanical properties of the ECM-mimetic systems has changed from the classical concept of elastic networks to mimic the viscoelastic behavior of the native tissue. Recently, the use of supramolecular chemistry has emerged as a promising strategy to achieve this behavior. In this work, alginate-based hydrogels were developed with a dual cross-linking system comprising dynamic cucurbit[8]uril host-guest homoternary complexes and covalent photo-cross-linking of methacrylate groups. By adjusting the ratio of covalent to dynamic bonds, control over the stress relaxation time scale was achieved, which offers an entry to mimic the viscoelastic properties of native soft tissues. Furthermore, this hydrogel formulation was found to be noncytotoxic and promotes cell survival, attachment, and alignment.