Dual Dynamic Covalently Crosslinked Alginate Hydrogels with Tunable Properties and Multiple Stimuli-Responsiveness

Alginate is a biopolymer that can be crosslinked with calcium ions to fabricate cytocompatible hydrogels. However, using calcium ions to crosslink alginate provides limited properties and functions to alginate hydrogels, restricting their biomedical applications. Here, phenylboronic acid-functionalized polyethyleneimine (PBA-PEI) was developed to introduce two orthogonal dynamic covalent crosslinks in the alginate hydrogels, where PBA-PEI was used to crosslink alginate dialdehyde (ADA) through imine bonds and boronate ester bonds. The grafting degree of PBA in the PEI structure was applied to fine-tune the properties of PBA-PEI/ADA hydrogels, including the rheological property, mechanical strength, swelling behavior, and antibacterial activity. In particular, the highly sensitive boronate ester bonds in the network enabled PBA-PEI/ADA hydrogels to be responsive to several stimuli, such as glucose, fructose, and hydrogen peroxide. Taken together, PBA-PEI/ADA hydrogels with tunable properties and multiple stimuli-responsiveness have been demonstrated as smart biomaterials for advanced biomedical applications.