title: Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model.
abstract: Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Linjiang
authors.initials: L
authors.lastname: Song
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Suleixin
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P. R. China.
authors.forename: Changyang
authors.initials: C
authors.lastname: Gong
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death; D002470:Cell Survival; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007267:Injections; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D010084:Oxidation-Reduction; D010537:Peritoneum / Q000473:pathology* / Q000648:ultrastructure; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology; D000267:Tissue Adhesions / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D001672:Biocompatible Materials; D017395:Plasminogen Activator Inhibitor 1; C077199:O,N-carboxymethylchitosan; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; D048271:Chitosan; D010959:Tissue Plasminogen Activator