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Thermoresponsive Polysaccharide-based Composite Hydrogel with Antibacterial and Healing-promoting Activities for Preventing Recurrent Adhesion after Adhesiolysis
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2018-05-24 , DOI: 10.1016/j.actbio.2018.05.037
Ershuai Zhang , Qi Guo , Feng Ji , Xinlu Tian , Jing Cui , Yihang Song , Hong Sun , Junjie Li , Fanglian Yao

Postoperative adhesions are very common complications after general abdominal surgery. Although adhesiolysis has been proven effective in eliminating the preexisting adhesions, the new trauma caused by surgical lysis can induce recurrent adhesion. The prevention of recurrent adhesion after adhesiolysis is more difficult because the injury is more severe and adhesion mechanism is more complicated compared with the primary adhesion. In this study, a thermoresponsive hydrogel contained galactose modified xyloglucan (mXG) and hydroxybutyl chitosan (HBC) was developed as a barrier device for recurrent adhesion prevention after adhesiolysis due to its injectability and spontaneous gelling behaviors at the body temperature without any chemical reactions or extra driving factors. First, mXG and HBC were synthesized via enzymatic modification and etherification reaction, respectively. Rheological measurements indicated that the mXG/HBC composite system showed excellent thermosensitivity properties, and their gelation temperature and time can be modulated via adjusting the mXG/HBC ratio. Moreover, the mXG/HBC hydrogel exhibited excellent cytocompatibility and hemocompatibility in vitro. Furthermore, the mXG/HBC hydrogel could promote wound healing in the rat skin wound model. Finally, the efficacy of the mXG/HBC composite hydrogel in the prevention of recurrent adhesion was evaluated in a more rigorous rat repeated-injury adhesion model. The results demonstrated that the composite hydrogel could not only effectively prevent recurrent adhesion after adhesiolysis, but also promote wound healing and reduce scare formation. These results suggested that the mXG/HBC composite hydrogel may be a promising candidate as an injectable anti-adhesion system for clinical applications.

Statement of Significance

Although adhesiolysis has been proven effective in eliminating the preexisting adhesions, the new trauma caused by surgical lysis can induce recurrent adhesion. So far, most of the existing barrier systems and pharmacological approaches were developed for primary adhesion prevention while few attention has paid on prevention of recurrent adhesion after adhesiolysis. In the present study, we developed a thermoresponsive polysaccharide-based composite hydrogel by simple mixing galactose modified xyloglucan (mXG) and hydroxybutyl chitosan (HBC). The resulting mXG/HBC composite hydrogel not only was easy to handle and highly effective in preventing the recurrent adhesion after adhesiolysis, but also could promote wound healing and reduce scare formation. Our study provide an effective anti-adhesion system for preventing recurrent adhesion after adhesiolysis.



中文翻译:

具有抗菌和促进愈合作用的热响应性多糖基复合水凝胶,可防止粘连后的反复粘连。

术后粘连是普通腹部手术后非常常见的并发症。尽管已经证明粘膜溶解可以有效消除先前存在的粘连,但是由外科手术溶解引起的新创伤可以引起复发性粘连。与初次粘连相比,由于损伤更严重并且粘连机制更复杂,因此预防粘连后复发粘连更加困难。在这项研究中,开发了一种含有半乳糖修饰的木葡聚糖(mXG)和羟丁基壳聚糖(HBC)的热响应性水凝胶,由于其在人体温度下的可注射性和自发胶凝行为而没有任何化学反应或其他作用,因此可作为一种防止粘连后复发粘连的屏障装置。驱动因素。首先,通过分别进行酶促修饰和醚化反应。流变学测量表明,mXG / HBC复合体系表现出优异的热敏性,可通过调节mXG / HBC比值调节其凝胶化温度和时间。此外,mXG / HBC水凝胶在体外表现出优异的细胞相容性和血液相容性。此外,mXG / HBC水凝胶可促进大鼠皮肤伤口模型的伤口愈合。最后,在更严格的大鼠反复损伤粘连模型中评估了mXG / HBC复合水凝胶在预防复发粘连中的功效。结果表明,复合水凝胶不仅可以有效地防止粘连后的再粘连,而且可以促进伤口愈合并减少疤痕形成。这些结果表明,mXG / HBC复合水凝胶可以作为可注射的抗粘连系统用于临床应用。

重要声明

尽管已经证明粘膜溶解可以有效消除先前存在的粘连,但是由外科手术溶解引起的新创伤可以引起复发性粘连。迄今为止,大多数现有的屏障系统和药理学方法都是为预防一级粘连而开发的,而很少有人关注预防粘连分解后的复发性粘连。在本研究中,我们通过简单混合半乳糖修饰的木葡聚糖(mXG)和羟丁基壳聚糖(HBC),开发了一种基于热响应性多糖的复合水凝胶。所得的mXG / HBC复合水凝胶不仅易于处理,并且在防止胶粘剂溶解后的反复粘连方面非常有效,而且可以促进伤口愈合并减少疤痕形成。

更新日期:2018-05-24
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