Thermoreversible Radial Growth of Micellar Assembly for Hydrogel Formation Using Zwitterionic Oligopeptide Copolymer

Abstract

Amphiphilic block copolymers can self-assemble into micelles in water and can further form thermosensitive gels. Here, we explored Pluronic F127 ABA triblock copolymer of poly(ethylene glycol) (PEG; A) and poly(propylene glycol) (PPG; B), modified with telechelic ionic peptides, either anionic Gly-Phe-Gly-Asp (GFGD) or zwitterionic Gly-Arg-Gly-Leu (GRGL) or Gly-Arg-Gly-Asp (GRGD). All block copolymers formed micelles, but only those bearing zwitterionic peptides formed thermoreversible nanoassembly of micellar aggregates. These aggregates facilitate to form a gel at high polymer concentrations, thus making the sol-to-gel transition temperature lower than F127 and FGM. An increase in the sol-to-gel transition temperature and a decrease in the gel modulus have been a concern for biomedical applications of hydrophobically modified Pluronics. Current zwitterionic modified Pluronic F127, on the contrary, decreased the sol-to-gel transition temperature without loss of the gel modulus. The gelation, evidenced by cryo-transmission electron microscopy images, involves radial growth of micelle aggregates, which is strikingly different from that of Pluronics driven by simple unimer-to-micelle transition. The RGD-containing copolymer is of particular interest, in that it is cytocompatible and capable of binding to cell-surface adhesion receptors. This work suggests a new platform in designing a temperature-sensitive polymer with a unique nanoassembly for tissue regeneration.