Solubilization of chitosan in biologically relevant solvents by a low-temperature solvent-exchange method for developing biocompatible chitosan materials

Chitosan has great potential for biomedical applications. However, the intractable solubility of chitosan is a major bottleneck hampering its utilization. In this work, we report a low-temperature solvent-exchange method to solubilize chitosan in biologically relevant solvents (bio-solvents) including water, salines, and cell culture media. Chitosan was firstly dissolved in ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate (EMIM Ac). The chitosan/IL solution was then dialyzed against bio-solvents at 4 degrees C, during which a solvent exchange process took place. At the end of 24 h dialysis, aqueous chitosan pseudosolutions formed. Low temperature is found to be crucial for efficient solubilization of chitosan during the solvent exchange process. Increasing temperature to 50 degrees C leads to the formation of solid chitosan hydrogel. Chitosan in the water-based pseudosolution presents as positively charged particles. The pseudosolution shows a high positive zeta potential of about +52.6 mV and good colloidal stability. The water-based pseudosolutions with different amounts of chitosan contents exhibit the rheological features of weak liquid gels. By using these pseudosolutions, the fabrication of various chitosan materials is realized readily. Both chitosan pseudosolution and its downstream products are highly biocompatible. In this strategy, using IL as a solvent-medium and processing a low-temperature solvent exchange are the two key parameters to solubilize chitosan.