Synthesis of PEGylated polypeptides bearing thioether pendants for injectable ROS-responsive hydrogels

Abstract Injectable hydrogels have gained massive attention in the past decade due to the simple operation, the ability to fill irregularly shaped wounds, and high safety. Herein, we design a PEGylated polypeptide with reactive oxygen species (ROS) responsiveness for injectable hydrogel. In brief, poly(ethylene glycol)-block-poly(2-methylthioethyl L-glutamate) was synthesized by ring opening polymerization of N -carboxylic anhydride with thioether group. The obtained amphiphilic copolymer could self-assemble into micelles, which underwent a sol–gel phase transition at 35°C. Carbon-13 nuclear magnetic resonance, dynamic light scattering, and circular dichroism measurements indicated that the partial dehydration of poly(ethylene glycol), the aggregation of micelles, and the change of β-sheet packing of PMLG 15 as temperature increasing were regarded as the main driving forces of gelation. The formed hydrogel was disrupted by 10 mM H 2 O 2 due to the oxidation of hydrophobic thioether groups into hydrophilic sulfoxides. Furthermore, in vitro experiment showed that the hydrogels consisting of thioether groups exhibited cytoprotective ability against the damage of H 2 O 2 -induced oxidative stress to L929 cells. Finally, the aqueous solution of this copolymer rapidly transformed into gel after being injected into the subcutaneous layer of mice.