Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention

被引：526

作者：

Li, Ling ^{[1
,2
]}

Wang, Ning ^{[1
,2
]}

Jin, Xun ^{[1
,2
]}

Deng, Rui ^{[1
,2
]}

Nie, Shihong ^{[1
,2
]}

Sun, Lu ^{[1
,2
]}

Wu, Qinjie ^{[1
,2
]}

Wei, Yuquan ^{[1
,2
]}

Gong, Changyang ^{[1
,2
]}

机构：

[1] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Peoples R China

[2] Sichuan Univ, West China Med Sch, West China Hosp, Ctr Canc, Chengdu 610041, Peoples R China

来源：

BIOMATERIALS | 2014年 / 35卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Postoperative adhesion; Chitosan; Hyaluronic acid; In situ cross-linkable hydrogel; Biodegradable; POSTSURGICAL ADHESIONS; PERITONEAL ADHESIONS; ABDOMINAL ADHESIONS; DRUG-DELIVERY; RAT MODEL; FIBRINOLYTIC AGENTS; DEXTRAN; PROLIFERATION; OBSTRUCTION; DERIVATIVES;

D O I：

10.1016/j.biomaterials.2014.01.050

中图分类号：

R318 [生物医学工程];

学科分类号：

100103 [病原生物学];

摘要：

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. (c) 2014 Elsevier Ltd. All rights reserved.

引用

页码：3903 / 3917

页数：15

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