An injectable and fast-degradable poly(ethylene glycol) hydrogel fabricated via bioorthogonal strain-promoted azide–alkyne cycloaddition click chemistry

Biocompatible and degradable injectable materials prepared via bioorthogonal reactions are highly promising for biomedical applications because they can be formed in situ and administered in a minimally invasive way. In this work, a PEG-based injectable hydrogel was fabricated via a copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry. Azide and cyclooctyne moieties on the PEG backbones underwent a rapid click reaction to trigger the formation of the hydrogel within several minutes. Resulting from the introduction of ester groups into the cross-linked network, the hydrogel presented pH-dependent hydrolysis and biological fast degradability. Good biocompatibility of the hydrogel was verified by in vitro cytotoxicity assay and in vivo studies. The hydrogel formed in situ after subcutaneously injecting the gel precursors into Kungming (KM) mice. The implanted hydrogel caused a mild inflammatory response in vivo, and the surrounding tissues fully recovered a week after the injection. The injectable and fast-degradable hydrogel fabricated by the bioorthogonal click reaction may be useful as biomaterials such as embolic agents for interventional therapy.