Aziz Manal A, Cabral Jaydee D, Brooks Heather J L, McConnell Michelle A, Fitzpatrick Clare, Hanton Lyall R, Moratti Stephen C
Department of Chemistry, University of Otago, Dunedin, New Zealand; Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
J Biomed Mater Res B Appl Biomater. 2015 Feb;103(2):332-41. doi: 10.1002/jbm.b.33206. Epub 2014 May 29.
In this paper, we report the in vitro biocompatibility and cellular interactions of a chitosan/dextran-based (CD) hydrogel and its components as determined by mutagenicity, cytotoxicity, cytokine/chemokine response, and wound healing assays. The CD hydrogel, developed for postsurgical adhesion prevention in ear, nose, and throat surgeries, was shown by previously published experiments in animal and human trials to be effective. The hydrogel was synthesized from the reaction between succinyl chitosan (SC) and oxidized dextran (DA). Cytotoxicity was assessed in an xCELLigence system and cytokine/chemokine responses were measured by ELISA in human macrophage, nasopharyngeal epithelial, and dermal fibroblast cells. A wound healing model utilized nasopharyngeal epithelial cells. CD hydrogel and DA were nonmutagenic in the Ames test. CD hydrogel showed moderate cytotoxicity for the cell lines, DA being the cytotoxic component. Some inhibition of wound healing occurred due to the cytotoxic nature of DA. Cells cultured with CD hydrogel showed no increase in TNF-α, IL-10, and IL-8 levels. It is hypothesized that the cytotoxicity of DA is moderated when reacted with SC and that CD hydrogel inhibits unwanted fibroblastic invasion preventing scarring and adhesions. Together with the previously published human and animal trial data, the results indicate CD hydrogel is biocompatible in the setting of endoscopic sinus surgery. This work represents the first study of CD hydrogel with human cell lines and provides essential information for its future application in biomedicine.
在本文中，我们报告了一种基于壳聚糖/葡聚糖（CD）的水凝胶及其成分的体外生物相容性和细胞相互作用，这些是通过致突变性、细胞毒性、细胞因子/趋化因子反应和伤口愈合试验来确定的。为预防耳鼻喉科手术后粘连而开发的CD水凝胶，在先前发表的动物和人体试验中已证明是有效的。该水凝胶由琥珀酰壳聚糖（SC）和氧化葡聚糖（DA）之间的反应合成。在xCELLigence系统中评估细胞毒性，并通过ELISA在人巨噬细胞、鼻咽上皮细胞和真皮成纤维细胞中测量细胞因子/趋化因子反应。伤口愈合模型使用鼻咽上皮细胞。CD水凝胶和DA在艾姆斯试验中无致突变性。CD水凝胶对细胞系显示出中等细胞毒性，DA是细胞毒性成分。由于DA的细胞毒性性质，伤口愈合受到了一些抑制。用CD水凝胶培养的细胞中TNF-α、IL-10和IL-8水平没有增加。据推测，DA与SC反应时其细胞毒性会降低，并且CD水凝胶可抑制不必要的成纤维细胞侵入，防止瘢痕形成和粘连。结合先前发表的人体和动物试验数据，结果表明CD水凝胶在内镜鼻窦手术中具有生物相容性。这项工作是对CD水凝胶与人细胞系的首次研究，并为其未来在生物医学中的应用提供了重要信息。
