title: Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention.
abstract: Postsurgical peritoneal adhesions are very common and serious complication after surgery. Biodegradable and injectable hydrogels derived from natural polysaccharides are ideal biomaterials for prevention of postoperative adhesion. In this work, we report a class of injectable, biodegradable, and non-toxic hydrogel derived from N, O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (A-HA), without requirement of any chemical linkers or radiant light sources. NOCC was prepared by introducing carboxymethyl groups to the N-position and the O-position of chitosan, and A-HA was prepared using periodate oxidation method. The gelation is attributed to the Schiff base between the amino groups of NOCC and aldehyde groups in A-HA, and the hydrogel precursors cross-linked to form a flexible hydrogel. NOCC, A-HA, and NOCC/A-HA hydrogel extract exhibited very low cytotoxicity and hemolysis, and the acute toxicity tests showed that the hydrogel was non-toxic. Besides, the highly porous three-dimensional hydrogel can supported the growth and proliferation of the cells encapsulated in the hydrogels, but was not favorable for the attachment of fibroblasts to the surface, suggesting that the NOCC/A-HA hydrogel can be developed for adhesion prevention. The hydrogel was susceptible to the lysozyme and can be degraded within 2 weeks in vivo. Furthermore, we employed a rat model of sidewall defect-cecum abrasion to investigate the efficacy of NOCC/A-HA hydrogel in preventing post-operative peritoneal adhesions. A significant reduction of peritoneal adhesion formation was found in the NOCC/A-HA-treated group, compared with commercial hyaluronic acid (HA) hydrogel group and normal saline group. In addition, the potential anti-adhesion mechanism of NOCC/A-HA hydrogel was discussed, which may attribute to the combination of barrier function and bioactivity of NOCC and A-HA.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors: Ling
authors: L
authors: Li
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors: Ning
authors: N
authors: Wang
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors: Xun
authors: X
authors: Jin
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors: Rui
authors: R
authors: Deng
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors: Shihong
authors: S
authors: Nie
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors: Lu
authors: L
authors: Sun
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors: Qinjie
authors: Q
authors: Wu
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors: Yuquan
authors: Y
authors: Wei
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address: chygong14@163.com.
authors: Changyang
authors: C
authors: Gong
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D011183:Postoperative Complications; D000267:Tissue Adhesions / Q000517:prevention & control*
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D006820:Hyaluronic Acid; D048271:Chitosan
keywords: Biodegradable; Chitosan; Hyaluronic acid; In situ cross-linkable hydrogel; Postoperative adhesion