Rational synthesis of novel biocompatible thermoresponsive block copolymer worm gels

It is well known that reversible addition-fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) enables the rational design of diblock copolymer worm gels. Moreover, such hydrogels can undergo degelation on cooling below ambient temperature as a result of a worm-to-sphere transition. However, only a subset of such block copolymer worms exhibit thermoresponsive behavior. For example, PMPC26-PHPMA280 worm gels prepared using a poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC26) precursor do not undergo degelation on cooling to 6 °C (see S. Sugihara et al., J. Am. Chem. Soc., 2011, 133, 15707-15713). Informed by our recent studies (N. J. Warren et al., Macromolecules, 2018, 51, 8357-8371), we decided to reduce the mean degrees of polymerization of both the PMPC steric stabilizer block and the structure-directing PHPMA block when targeting a pure worm morphology. This rational approach reduces the hydrophobic character of the PHPMA block and hence introduces the desired thermoresponsive character, as evidenced by the worm-to-sphere transition (and concomitant degelation) that occurs on cooling a PMPC15-PHPMA150 worm gel from 40 °C to 6 °C. Moreover, worms are reconstituted on returning to 40 °C and the original gel modulus is restored. This augurs well for potential biomedical applications, which will be examined in due course. Finally, small-angle X-ray scattering studies indicated a scaling law exponent of 0.67 (≈2/3) for the relationship between the worm core cross-sectional diameter and the PHPMA DP for a series of PHPMA-based worms prepared using a range of steric stabilizer blocks, which is consistent with the strong segregation regime for such systems.