Thermoresponsive polysaccharide-based composite hydrogel with antibacterial and healing-promoting activities for preventing recurrent adhesion after adhesiolysis

Abstract

Postoperative adhesions are very common complications after general abdominal surgery. Although adhesiolysis has been proven effective in eliminating the preexisting adhesions, the new trauma caused by surgical lysis can induce recurrent adhesion. The prevention of recurrent adhesion after adhesiolysis is more difficult because the injury is more severe and adhesion mechanism is more complicated compared with the primary adhesion. In this study, a thermoresponsive hydrogel contained galactose modified xyloglucan (mXG) and hydroxybutyl chitosan (HBC) was developed as a barrier device for recurrent adhesion prevention after adhesiolysis due to its injectability and spontaneous gelling behaviors at the body temperature without any chemical reactions or extra driving factors. First, mXG and HBC were synthesized via enzymatic modification and etherification reaction, respectively. Rheological measurements indicated that the mXG/HBC composite system showed excellent thermosensitivity properties, and their gelation temperature and time can be modulated via adjusting the mXG/HBC ratio. Moreover, the mXG/HBC hydrogel exhibited excellent cytocompatibility and hemocompatibility in vitro. Furthermore, the mXG/HBC hydrogel could promote wound healing in the rat skin wound model. Finally, the efficacy of the mXG/HBC composite hydrogel in the prevention of recurrent adhesion was evaluated in a more rigorous rat repeated-injury adhesion model. The results demonstrated that the composite hydrogel could not only effectively prevent recurrent adhesion after adhesiolysis, but also promote wound healing and reduce scare formation. These results suggested that the mXG/HBC composite hydrogel may be a promising candidate as an injectable anti-adhesion system for clinical applications. Statement of SignificanceAlthough adhesiolysis has been proven effective in eliminating the preexisting adhesions, the new trauma caused by surgical lysis can induce recurrent adhesion. So far, most of the existing barrier systems and pharmacological approaches were developed for primary adhesion prevention while few attention has paid on prevention of recurrent adhesion after adhesiolysis. In the present study, we developed a thermoresponsive polysaccharide-based composite hydrogel by simple mixing galactose modified xyloglucan (mXG) and hydroxybutyl chitosan (HBC). The resulting mXG/HBC composite hydrogel not only was easy to handle and highly effective in preventing the recurrent adhesion after adhesiolysis, but also could promote wound healing and reduce scare formation. Our study provide an effective anti-adhesion system for preventing recurrent adhesion after adhesiolysis.