Regulating the Homogeneity of Thiol-Maleimide Michael-Type Addition-Based Hydrogels Using Amino Biomolecules

Poly(ethylene glycol) (PEG)-based synthetic hydrogels based on Michael-type addition reaction have been widely used for cell culture and tissue engineering. However, recent studies showed that these types of hydrogels were not homogenous as expected since micro domains generated due to the fast reaction kinetics. Here, we demonstrated a new kind of method to prepare homogenous poly(ethylene glycol) hydrogels based on Michael-type addition using the side chain amine-contained short peptides. By introducing such a kind of short peptides, the homogeneity of crosslinking and mechanical property of the hydrogels has been also significantly enhanced. The compressive mechanical and recovery properties of the homogeneous hydrogels prepared in the presence of side chain amine-contained short peptides were more reliable than those of inhomogeneous hydrogels while the excellent biocompatibility remained unchanged. Furthermore, the reaction rate and gelation kinetics of maleimide- and thiol-terminated PEG were proved to be significantly slowed down in the presence of the side chain amine-contained short peptides, thus leading to the improved homogeneity of the hydrogels. We anticipate that this new method can be widely applied to hydrogel preparation and modification based on Michael-type addition gelation.