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含碱性成纤维细胞生长因子的明胶水凝胶促进肠道吻合口愈合

Enhanced intestinal anastomotic healing with gelatin hydrogel incorporating basic fibroblast growth factor.

作者信息

Hirai Kenjiro, Tabata Yasuhiko, Hasegawa Suguru, Sakai Yoshiharu

机构信息

Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Japan.

Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Japan.

出版信息

J Tissue Eng Regen Med. 2016 Oct;10(10):E433-E442. doi: 10.1002/term.1835. Epub 2013 Oct 16.

Abstract

Anastomotic leakage is a common complication of intestinal surgery. In an attempt to resolve this issue, a promising approach is enhancement of anastomotic wound healing. A method for controlled release of basic fibroblast growth factor (bFGF) using a gelatin hydrogel was developed with the objective of investigating the effects of this technology on intestinal anastomotic healing. The small intestine of Wistar rats was cut, end-to-end anastomosis was performed and rats were divided into three groups: bFGF group (anastomosis wrapped with a hydrogel sheet incorporating bFGF), PBS group (wrapped with a sheet incorporating phosphate-buffered saline solution) and NT group (no additional treatment). Degradation profiles of gelatin hydrogels in vivo and histological examinations were performed using gelatin hydrogels with various water contents and bFGF concentrations to define the optimal bFGF dose and hydrogel biodegradability. The anastomotic wound healing process was evaluated by histological examinations, adhesion-related score and bursting pressure. The optimal water content of the hydrogel and bFGF dose was determined as 96% and 30 µg per sheet, respectively. Application of bFGF significantly enhanced neovascularization, fibroblast infiltration and collagen production around the anastomotic site when compared with the other groups. Bursting pressure was significantly increased in the bFGF group. No significant difference was observed in the adhesion-related score among the groups and no anastomotic obstruction and leakage were observed. Therefore controlled release of bFGF enhanced healing of an intestinal anastomosis during the early postoperative period and is a promising method to suppress anastomotic leakage. Copyright © 2013 John Wiley & Sons, Ltd.

摘要

吻合口漏是肠道手术的常见并发症。为解决这一问题,一种有前景的方法是促进吻合口伤口愈合。为研究该技术对肠道吻合口愈合的影响,开发了一种使用明胶水凝胶控制释放碱性成纤维细胞生长因子(bFGF)的方法。将Wistar大鼠的小肠切断,进行端端吻合,并将大鼠分为三组:bFGF组(用含bFGF的水凝胶片包裹吻合口)、PBS组(用含磷酸盐缓冲盐溶液的片包裹)和NT组(不进行额外处理)。使用具有不同含水量和bFGF浓度的明胶水凝胶进行体内降解曲线研究和组织学检查,以确定最佳bFGF剂量和水凝胶生物降解性。通过组织学检查、粘连相关评分和破裂压力评估吻合口伤口愈合过程。水凝胶的最佳含水量和bFGF剂量分别确定为96%和每张30μg。与其他组相比,bFGF的应用显著增强了吻合口周围的新生血管形成、成纤维细胞浸润和胶原蛋白生成。bFGF组的破裂压力显著增加。各组之间在粘连相关评分上未观察到显著差异,也未观察到吻合口梗阻和漏出。因此,bFGF的控释可促进术后早期肠道吻合口的愈合,是一种有前景的抑制吻合口漏的方法。版权所有©2013约翰威立父子有限公司。

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