Single step synthesis and characterization of thermoresponsive hyaluronan hydrogels

An efficient and scale-up ready single-step synthesis for the conjugation of thermoresponsive polymers to hyaluronic acid (HA) was established. Jeffamines® (JFM) and poly(N-isopropylacrylamide) (PNIPAM) were grafted to HA via direct amidation mediated by 1,1′-carbonyldiimidazole activation. The temperature-induced gelation of the semi-synthetic co-polymers was characterized by rheology as a function of the temperature and by differential scanning calorimetry (DSC). A HA–JFM conjugate with sol–gel transition in a physiologically relevant temperature range was identified. The grafting of PNIPAM resulted in the drastic change of the main rheological properties of native HA, revealing the hydrophobic non-covalent nature of the interactions between the thermoresponsive brushes in the gel state. Owing to the reversibility of these interactions and the sharpness of the transition, the HA–PNIPAM conjugates are suitable candidates for the incorporation of drugs, cells or ceramic materials for different biomedical applications.