Partial sulfation of gellan gum produces cytocompatible, body temperature-responsive hydrogels

Gellan gum (GG) is a biodegradable polysaccharide and forms thermosensitive hydrogels by a helix-mediated mechanism. Unfortunately, the wide use of GG in tissue engineering has been restricted due to its dramatically higher gelation temperature than normal body temperature. Here, we show that partial sulfation of GG affords a cytocompatible body temperature-responsive hydrogel with an interesting thermoreversibility at 42 °C. The partial sulfation of GG was confirmed by FTIR, EDX and elemental analyses. The sulfated GGs (SGGs) had a higher swelling ratio and degradation in PBS compared to the neat GG. Based on the results of rheometry analysis, the SGG with a degree of sulfation of 0.27 (H3 sample) showed a gelation temperature close to the physiological temperature. In addition, the drop in mechanical properties of SGGs was compensated by a further calcium-mediated ionic crosslinking, where Young's modulus of H3 increased from 10.6 ± 1.9 kPa up to 38.4 ± 5.5 kPa. Finally, we showed that the partial sulfation reaction of GG is a simple and mild strategy to modify chemical structure of GG, and to produce a cytocompatible, body temperature-responsive hydrogel compared to other modifying reactions such as oxidation reaction.