Abstract: Injectable hydrogels are ideal biomaterials for delivering cells, growth factors and drugs specifically to localized lesions and subsequent controlled release. Many factors can affect the efficacy of injectable hydrogels. To avoid potential damage to encapsulated cells or drugs, injectable hydrogels should be highly dynamic so that they can undergo shear-thinning at low strain rates and rapidly reform after injection. However, dynamic hydrogels are often mechanically weak, leading to the leakage of encapsulated cells or drugs. Here we demonstrated a convenient method to improve the mechanical strength without jeopardizing the dynamic properties of hydrogels by using metal ion-peptide crosslinkers containing multiple metal ion-ligand bonds. We showed that the dynamic properties of the hydrogels correlated with the intrinsic dynamics of the metal-ligand bonds and were not affected by the formation of multivalent binding. Yet, the mechanical stability of the hydrogels was significantly improved due to the increased thermodynamic stability of the crosslinkers. We further showed that the drug release rates were slowed down by the formation of multivalent crosslinkers. Our results highlight the importance of ligand valency to the mechanical response of hydrogels and provide a universal route to rationally tune the dynamic and mechanical properties of injectable hydrogels.

Key words: Peptide-ion coordination, Ligand cooperativity, Injectable hydrogel, Mechanical response