Reproducible Dendronized PEG Hydrogels via SPAAC Cross-Linking

A common issue with hydrogel formulations is batch-to-batch irreproducibility originating from poorly defined polymer precursors. Here, we report the use of dendritic polymer end-groups to address this issue and maintain reproducibility between batches of poly(ethylene glycol) (PEG) hydrogels. Specifically, we synthesized two end-functionalized PEG chains: one with azide-terminated first- and second-generation dendrons and the other with strained cyclooctynes. The two complementary azide and alkyne polymers react via strain-promoted alkyne-azide cycloaddition (SPAAC) to produce hydrogels quickly in the absence of additional reagents or catalyst at low polymer concentrations. Hydrogels made with first-generation dendrons gelled in minutes and exhibited a small degree of swelling when incubated in PBS buffer at 37 °C, whereas hydrogels made from second-generation dendrons gelled in seconds with almost no swelling upon incubation at 37 °C. In both cases, the hydrogels proved reproducible, resulting in identical Young's modulus values from different batches. The hydrogels prepared with second-generation dendrons were seeded with human mesenchymal stem cells and showed high cell viability as well as cell spreading over a two-week time frame. These studies show that the SPAAC hydrogels are noncytotoxic and are capable of supporting cell growth.