Thermoresponsive hydrogels formed by poly(2-oxazoline) triblock copolymers

Hydrogels are useful materials for drug delivery and tissue engineering. A subset of these are responsive hydrogelators that are liquids until a stimulus triggers their gelation. Poly(2-oxazoline)s with moderately hydrophobic side chains, such as ethyl and propyl, are inherently thermoresponsive exhibiting lower critical solution temperature behavior. However, previous attempts to make thermoresponsive poly(2-oxazoline) block copolymer hydrogelators have all failed. In this work we report the first working thermoresponsive poly(2-oxazoline) hydrogelator based on ABA triblock copolymers with thermoresponsive outer blocks composed of poly(2-n-propyl-2-oxazoline) and a more hydrophilic poly(2-ethyl-2-oxazoline) inner block that can form hydrogels upon heating an aqueous solution. It was found that thermoresponsive hydrogels are only formed if the block size is tuned to adjust the cloud point temperature and, presumably, to allow sufficient flexibility to non-covalently crosslink the flower-like micelles that these materials form. These triblocks copoly(2-oxazoline)s formed relatively soft thermoresponsive hydrogels that could be suitable for drug release and cell culture applications.