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

Xiaojie Lv; Yunen Liu; Subin Song; Changci Tong; Xiuyun Shi; Yan Zhao; Jinsong Zhang; Mingxiao Hou

doi:10.1016/j.carbpol.2018.10.067

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

Carbohydr Polym. 2019 Feb 1:205:312-321. doi: 10.1016/j.carbpol.2018.10.067. Epub 2018 Oct 28.

Authors

Xiaojie Lv¹, Yunen Liu², Subin Song³, Changci Tong², Xiuyun Shi², Yan Zhao⁴, Jinsong Zhang⁵, Mingxiao Hou²

Affiliations

¹ Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang, 110016, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
² Department of Emergency Medicine, General Hospital of Shenyang Military Command, Shenyang, 110016, PR China.
³ Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang, 110016, PR China.
⁴ Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang, 110016, PR China. Electronic address: yanzhao@imr.ac.cn.
⁵ Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang, 110016, PR China. Electronic address: jshzhang@imr.ac.cn.

PMID: 30446110
DOI: 10.1016/j.carbpol.2018.10.067

Abstract

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.

Keywords: Chitosan oligosaccharide; Electrostatic interactions; Injectable hydrogels; Storage modulus; Wound healing.