Injectable thermosensitive chitosan hydrogels with controlled gelation kinetics and enhanced mechanical resistance

The use of injectable hydrogels is presently limited by the difficulty to achieve rapid gelation, high mechanical resistance and excellent cytocompatibility. In our study, high-strength injectable thermosensitive hydrogels of unmodified chitosan (CH) were obtained by combining sodium hydrogen carbonate (SHC) with phosphate buffer (PB) or beta-glycerophosphate (BGP) as gelling agents. A synergic effect led to the acceleration of gelation and a remarkable improvement of the storage modulus (G') of the hydrogels. Furthermore, the new hydrogels exhibited drastically enhanced Young moduli and resistance in compression as compared to conventional hydrogels prepared with BGP, PB or their combination. This was achieved while reducing the total salt concentration in the hydrogels. The gelation was rapid and the hydrogels presented porous structures and physiological pH, and did not show any cytotoxicity to L929 fibroblast cells in vitro. Overall, these new hydrogels provide interesting alternatives for use as blood vessel embolizing agents or as injectable scaffolds for drug delivery and/or cell seeding in tissue engineering strategies.