Injectable polyoxazoline grafted hyaluronic acid thermoresponsive hydrogels for biomedical applications.

Injectable thermosensitive hydrogels based on hyaluronic acid (HA) grafted with lower critical solution temperature (LCST) polyoxazoline (copolymers of poly(isopropyl- co -butyl oxazoline)) or P(iPrOx- co -BuOx) have been elaborated with tunable solution/gel temperature transitions and gel state elastic modulus. A suitable HA- g -P(iPrOx- co -BuOx-67/33)-0.10 sample with an iPrOx/BuOx ratio of 67/33, a polymerization degree (DP) of 25, a substitution degree (DS) of 10%, and displaying thermally induced gelling character with elastic ( G ') and viscous ( G '') moduli crossover points at 25 °C and a G ' at 37 °C around 80 Pa has been chosen for medical application. Hydrogels obtained with HA- g -P(iPrOx- co -BuOx-67/33)-0.10 exhibited high stability at 37 °C and excellent injectability properties with full and quick reversibility. The incorporation of a secondary network (HA), until 35 wt%, into the thermosensitive hydrogel also demonstrated very good stability and injectability.