Rapidly curable chitosan–PEG hydrogels as tissue adhesives for hemostasis and wound healing

Chitosan–poly(ethylene glycol)–tyramine (CPT) hydrogels were rapidly formed in situ using horseradish peroxidase and hydrogen peroxide to explore their performance as efficient tissue adhesives. A poly(ethylene glycol) modified with tyramine was grafted onto a chitosan backbone to enhance the solubility of the chitosan and to crosslink into three-dimensional networks. The elastic modulus of the hydrogels could be controlled by changing the crosslinking conditions, and the mechanical strength influenced the tissue adhesiveness of the hydrogels. The hydrogels showed the adhesiveness ranging from 3- to 20-fold that of fibrin glue (Greenplast®). The hemostatic ability of the hydrogels was evaluated on the basis that bleeding from liver defects was significantly arrested by the combined effect of the adhesiveness of the hydrogels and the hemostatic property of the chitosan materials. The enzymatic crosslinking method enabled the water-soluble chitosan to rapidly form hydrogels within 5 s of an incision into the skin of rats. Histological results demonstrated that the CPT hydrogels showed superior healing effects in the skin incision when compared to suture, fibrin glue and cyanoacrylate. By 2 weeks post-implantation, the wound was completely recovered, with a newly formed dermis, due to the presence of the CPT hydrogels in the incision. These results suggest that the in situ curable chitosan hydrogels are very interesting and promising tissue adhesive devices for biomedical applications.