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使用壳聚糖绷带预防小鼠高度污染伤口引发的致命感染。

Use of chitosan bandage to prevent fatal infections developing from highly contaminated wounds in mice.

作者信息

Burkatovskaya Marina, Tegos George P, Swietlik Emilia, Demidova Tatiana N, P Castano Ana, Hamblin Michael R

机构信息

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.

出版信息

Biomaterials. 2006 Aug;27(22):4157-64. doi: 10.1016/j.biomaterials.2006.03.028. Epub 2006 Apr 17.

Abstract

HemCon bandage is an engineered chitosan acetate preparation used as a hemostatic control dressing, and its chemical structure suggests that it should also be antimicrobial. We tested its ability to rapidly kill bacteria in vitro and in mouse models of infected wounds. We used the Gram-negative species Pseudomonas aeruginosa and Proteus mirabilis and the Gram-positive Staphylococcus aureus that had all been stably transduced with the entire bacterial lux operon to allow in vivo bioluminescence imaging. An excisional wound in Balb/c mice was inoculated with 50-250 million cells followed after 30 min by application of HemCon bandage, alginate sponge bandage, silver sulfadiazine cream or no treatment. HemCon was more adhesive to the wound and conformed well to the injury compared to alginate. Animal survival was followed over 15 days with observations of bioluminescence emission and animal activity daily. Chitosan acetate treated mice infected with P. aeruginosa and P. mirabilis all survived while those receiving no treatment, alginate and silver sulfadiazine demonstrated 25-100% mortality. Chitosan acetate was much more effective than other treatments in rapidly reducing bioluminescence in the wound consistent with its rapid bactericidal activity in vitro as well as its light-scattering properties. S. aureus formed only non-lethal localized infections after temporary immunosuppression of the mice but HemCon was again more effective in reducing bioluminescence. The data suggest that chitosan acetate rapidly kills bacteria in the wound before systemic invasion can take place, and is superior to alginate bandage and silver sulfadiazine that may both encourage bacterial growth in the short term.

摘要

HemCon绷带是一种经加工的醋酸壳聚糖制剂,用作止血控制敷料,其化学结构表明它也应具有抗菌性。我们测试了它在体外以及感染伤口小鼠模型中快速杀灭细菌的能力。我们使用了革兰氏阴性菌铜绿假单胞菌和奇异变形杆菌,以及革兰氏阳性菌金黄色葡萄球菌,这些细菌均已被整个细菌荧光素酶操纵子稳定转导,以进行体内生物发光成像。给Balb/c小鼠的切除伤口接种5000万至2.5亿个细胞,30分钟后应用HemCon绷带、藻酸盐海绵绷带、磺胺嘧啶银乳膏或不进行处理。与藻酸盐相比,HemCon对伤口的粘附性更强,与伤口的贴合度更好。对动物进行15天的存活观察,每天观察生物发光发射和动物活动情况。感染铜绿假单胞菌和奇异变形杆菌的醋酸壳聚糖处理小鼠全部存活,而未接受处理、使用藻酸盐和磺胺嘧啶银的小鼠死亡率为25%-100%。醋酸壳聚糖在快速降低伤口生物发光方面比其他处理方法有效得多,这与其在体外的快速杀菌活性以及光散射特性一致。在对小鼠进行临时免疫抑制后,金黄色葡萄球菌仅形成非致命性局部感染,但HemCon在降低生物发光方面再次更有效。数据表明,醋酸壳聚糖在全身感染发生之前能迅速杀灭伤口中的细菌,并且优于藻酸盐绷带和磺胺嘧啶银,后两者可能在短期内促进细菌生长。

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