Polydopamine Nanoparticle-Loaded Antifreezing and Photothermal Organohydrogel Based on Pullulan for Frostbite Therapy

Rapid rewarming is the standard and most common strategy for treating frostbite. Due to freezing susceptibility and lack of thermal effects, traditional therapeutic hydrogels are not suitable for being directly applied to frostbite therapy in cold conditions. Contrastively, antifreezing and photothermal hydrogels that are not apt to freeze and capable of rewarming frostbite wounds are deemed to hold great application potential in such therapy. Nevertheless, these hydrogels have rarely been researched. Herein, using glycerol as the cryoprotectant and polydopamine nanoparticles (PDA NPs) as the photothermal agent, a novel pullulan-based antifreezing and photothermal organohydrogel (CPG-PDA organohydrogel) was successfully developed to treat frostbite for the first time. The CPG-PDA organohydrogel formed through 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride (EDC·HCl)-mediated esterification reactions was found to possess certain mechanical stability, shear-thinning behaviors (injectability), excellent antifreezing properties, superb <i>in vitro</i> and <i>in vivo</i> photothermal performances, and outstanding cytocompatibility and hemocompatibility. Most noticeably, the photothermal rewarming and coating therapy using the CPG-PDA organohydrogel was observed to significantly accelerate the frostbite healing of rats. The CPG-PDA organohydrogel was opined to be a promising platform for the direct treatment of frostbite in a cold environment and would open a new avenue for the design of therapeutic strategies for frostbite.