Thermoreversible block copolymer worm gels using binary mixtures of PEG stabilizer blocks

Two trithiocarbonate-based poly(ethylene glycol) (PEG) macromolecular chain transfer agents (macro-CTAs) with mean degrees of polymerization of 45 and 113 were prepared with ≥94% chain-end functionality. Binary mixtures of these PEG–trithiocarbonate macro-CTAs were then chain-extended via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA). Systematic variation of the relative proportions of PEG45 and PEG113 macro-CTAs and the degree of polymerization of the PHPMA core-forming block resulted in the formation of [x PEG45 + z PEG113] – PHPMAn block copolymer spheres, worms, or vesicles, where x and z represent the mole fractions of PEG45 and PEG113, respectively. A phase diagram was constructed to establish the relationship between block copolymer composition and nanoparticle morphology. The thermoresponsive behavior of block copolymer worms was assessed by visual inspection, dynamic light scattering (DLS), transmission electron microscopy (TEM) and temperature-dependent oscillatory rheology. Increasing the proportion of PEG45 (x = 0.00–0.40) in the stabilizer block resulted in a moderate increase in worm gel strength, but cooling resulted in irreversible degelation owing to a worm-to-sphere morphology transition. However, the phase diagram enabled identification of a single diblock copolymer composition that exhibited reversible degelation behavior in pure water. This formulation was then further optimized to exhibit the same rheological behavior in a commercial cell culture medium (Nutristem) by fixing the PEG mole fraction at x = 0.70 while lowering the PHPMA DP from 115 to 75. Importantly, the gel strength at physiological temperature can be readily tuned simply by variation of the copolymer concentration. In principle, this study has important implications for the preservation of human stem cells, which can enter stasis when immersed in certain worm gels [see: Canton et al. ACS Cent. Sci. 2016, 2, 65–74].