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通过冻融技术制备的物理交联透明质酸基超软水凝胶作为预防术后粘连的屏障。

Physically Cross-Linked Hyaluronan-Based Ultrasoft Cryogel Prepared by Freeze-Thaw Technique as a Barrier for Prevention of Postoperative Adhesions.

机构信息

Advanced Rheology Institute, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.

Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P. R. China.

出版信息

Biomacromolecules. 2021 Dec 13;22(12):4967-4979. doi: 10.1021/acs.biomac.1c00878. Epub 2021 Sep 9.

DOI:10.1021/acs.biomac.1c00878
PMID:34499463
Abstract

Postsurgical peritoneal adhesions are a common and serious postoperative complication after various peritoneal surgeries, such as pelvic and abdominal surgery. Various studies have shown that peritoneal adhesions can be minimized or prevented by physical anti-adhesion barriers, including membranes, knits, and hydrogels. Hydrogels have attracted great attention in preventing peritoneal adhesions because the dimensional architecture of hydrogels is similar to that of the native extracellular matrix. However, chemical cross-linkers had to be used in the preparation of chemical hydrogels, which may have problems in cytotoxicity or unwanted side effects. This fact prompts us to create alternative cross-linking methods for the development of biocompatible hydrogels as physical barriers. Herein, we report a physically cross-linked flexible hyaluronan (HA) cryogel prepared a freeze-thaw technique as a novel anti-adhesion biomaterial for completely preventing postsurgical peritoneal adhesions. studies demonstrated that this physically cross-linked HA cryogel exhibited excellent biocompatibility, the inherently desirable biocompatibility and functionality of HA being integrally retained as much as possible. Intriguingly, the rheological properties and appropriate biodegradability of the cryogels were readily tailored and tunable by way of the gelation process. assessments suggested that the cryogel, as a physical barrier, satisfactorily prevented fibroblast penetration and attachment between the injured tissues and nearby normal organs. Furthermore, the molecular mechanism studies revealed that the HA cryogel could prevent peritoneal adhesion by inhibiting inflammatory response and modulation of the fibrinolytic system. Our results show that HA ultrasoft cryogel is a promising clinical candidate for prolonged adhesion prevention.

摘要

术后腹膜粘连是各种腹膜手术后(如盆腔和腹部手术)常见且严重的术后并发症。多项研究表明,通过物理性防粘连屏障(包括膜、针织品和水凝胶)可以将腹膜粘连最小化或预防。水凝胶在预防腹膜粘连方面引起了极大关注,因为水凝胶的尺寸结构与天然细胞外基质相似。然而,在制备化学水凝胶时必须使用化学交联剂,这可能在细胞毒性或不良副作用方面存在问题。这一事实促使我们开发替代交联方法,以用于开发作为物理屏障的生物相容性水凝胶。在此,我们报告了一种通过冻融技术制备的物理交联的柔性透明质酸(HA)水凝胶,作为一种新型的抗粘连生物材料,可完全预防术后腹膜粘连。多项研究表明,这种物理交联的 HA 水凝胶具有优异的生物相容性,HA 固有的理想生物相容性和功能尽可能完整地保留。有趣的是,通过凝胶化过程可以轻松地调整和调节水凝胶的流变性能和适当的生物降解性。评估表明,水凝胶作为物理屏障,可满意地防止成纤维细胞穿透以及受损组织与附近正常器官之间的粘连。此外,分子机制研究表明,HA 水凝胶可通过抑制炎症反应和纤维蛋白溶解系统的调节来预防腹膜粘连。我们的结果表明,HA 超软水凝胶是一种有前途的临床候选物,可用于延长粘连预防。

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