Influence of chitosan oligosaccharide on the gelling and wound healing properties of injectable hydrogels based on carboxymethyl chitosan/alginate polyelectrolyte complexes.

In situ injectable hydrogels for wound healing based on carboxymethyl chitosan (CMCS) and alginate were developed in this work. The liquid mixture of CMCS and alginate solutions formed a gel by polyelectrolyte complexation after addition of d-glucono-δ-lactone (GDL), which slowly hydrolyzed and donated protons. When chitosan oligosaccharide (COS) was added into the mixture, a two-stage gelling process occurred. The primary gelling process was similar to that of the hydrogel without COS, while the secondary gelling process appeared about 20 min later, and much stronger hydrogels with storage modulus G' about 1 MPa, 104 times higher, were obtained. COS also significantly influenced the microstructure of hydrogels as well as their biological activities. The hydrogels with 0.5% of COS significantly promoted proliferation of human umbilical cord mesenchymal stem cells (HUMSCs). These injectable hydrogels, especially when COS was added, remarkably accelerated the wound healing process in a mouse skin defect model. Microscopic wound analysis showed an increase of the thickness and integrity of epidermal tissue, increased formation of collagen fibers, and enhanced expression of vascular endothelial growth factor as compared to the control group.