Effect of pH on the Properties of Hydrogels Cross-Linked via Dynamic Thia-Michael Addition Bonds

[Image: see text] Hydrogels cross-linked with dynamic covalent bonds exhibit time-dependent properties, making them an advantageous platform for applications ranging from biomaterials to self-healing networks. However, the relationship between the cross-link exchange kinetics, material properties, and stability of these platforms is not fully understood, especially upon addition of external stimuli. In this work, pH was used as a handle to manipulate cross-link exchange kinetics and control the resulting hydrogel mechanics and stability in a physiologically relevant window. Poly(ethylene glycol)-based hydrogels were cross-linked with a reversible thia-Michael addition reaction in aqueous buffer between pH 3 and pH 7. The rate constants of bond exchange and equilibrium constants were determined for each pH value, and these data were correlated with the resulting mechanical profiles of the bulk hydrogels. With increasing pH, both the forward and the reverse rate constants increased, while the equilibrium constant decreased. These changes led to faster stress relaxation and less stiff hydrogels at more basic pH values. The elevated pH values also led to an increased mass loss and a faster rate of release of an encapsulated model bovine serum albumin fluorescent protein. The connection between the kinetics, mechanics, and molecular release profiles provides important insight into the structure–property relationships of dynamic covalent hydrogels, and this system offers a promising platform for controlled release between physiologically relevant pH values.