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基于双标记壳聚糖-葡聚糖的水凝胶用于预防术后粘连的体内宿主反应表征。

Characterization of the in vivo host response to a bi-labeled chitosan-dextran based hydrogel for postsurgical adhesion prevention.

作者信息

Cabral Jaydee D, McConnell Michelle A, Fitzpatrick Clare, Mros Sonya, Williams Gail, Wormald Peter J, Moratti Stephen C, Hanton Lyall R

机构信息

Department of Chemistry, University of Otago, Dunedin, 9054, New Zealand.

Department of Microbiology & Immunology, University of Otago, Dunedin, 9054, New Zealand.

出版信息

J Biomed Mater Res A. 2015 Aug;103(8):2611-20. doi: 10.1002/jbm.a.35395. Epub 2014 Dec 31.

Abstract

In developing a chitosan/dextran-based (CD) hydrogel as an adhesion prevention postsurgical aid, the in vivo biodegradation rate, biodistribution, and inflammatory response are important parameters to the biomedical device design. Herein, for the first time, a CD hydrogel was prepared by mixing aqueous solutions of a near infrared (NIR) labeled succinylated chitosan (SC) and tritiated [(3) H] oxidized dextran (DA). The biodegradation and biodistribution of the NIR/[(3) H]-CD hydrogel was tracked noninvasively using NIR fluorescence imaging, and by liquid scintillation counting (LSC) of organs/tissues after subcutaneous injection in BALB/c mice. The inflammatory response was assessed by measuring serum cytokine levels using a Bio-plex assay and by histological examination of injection site tissue. Fluorescence imaging showed the hydrogel to degrade in under a week. LSC revealed the hydrogel to reside mainly at the injection site, and excreted primarily via the urine within the first 48 h. The CD hydrogel showed a mild inflammatory response as cytokine levels were comparable to saline injected controls. Histological examination of injection site tissue confirmed the cytokine results. In summary, the CD hydrogel's in vivo biodegradation rate, biodistribution, and inflammatory response was determined. Our results indicate that the CD hydrogel has an appropriate biocompatibility after s.c. administration.

摘要

在研发一种基于壳聚糖/葡聚糖(CD)的水凝胶作为术后防粘连辅助材料时,体内生物降解速率、生物分布和炎症反应是生物医学装置设计的重要参数。在此,首次通过混合近红外(NIR)标记的琥珀酰化壳聚糖(SC)水溶液和氚化[³H]氧化葡聚糖(DA)水溶液制备了CD水凝胶。使用NIR荧光成像以及对BALB/c小鼠皮下注射后器官/组织进行液体闪烁计数(LSC),对NIR/[³H]-CD水凝胶的生物降解和生物分布进行了非侵入性追踪。通过使用生物芯片分析测量血清细胞因子水平以及对注射部位组织进行组织学检查来评估炎症反应。荧光成像显示水凝胶在一周内降解。LSC显示水凝胶主要驻留在注射部位,并在最初48小时内主要通过尿液排出。由于细胞因子水平与注射生理盐水的对照组相当,CD水凝胶显示出轻微的炎症反应。注射部位组织的组织学检查证实了细胞因子检测结果。总之,确定了CD水凝胶的体内生物降解速率、生物分布和炎症反应。我们的结果表明,CD水凝胶皮下给药后具有适当的生物相容性。

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