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具有协同抗菌活性以促进感染伤口愈合的氧化石墨烯-季铵纳米复合材料的合成。

Synthesis of graphene oxide-quaternary ammonium nanocomposite with synergistic antibacterial activity to promote infected wound healing.

作者信息

Liu Tengfei, Liu Yuqing, Liu Menglong, Wang Ying, He Weifeng, Shi Gaoqiang, Hu Xiaohong, Zhan Rixing, Luo Gaoxing, Xing Malcolm, Wu Jun

机构信息

1Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University, Chongqing, China.

Chongqing Key Laboratory for Disease Proteomics, Chongqing, China.

出版信息

Burns Trauma. 2018 May 21;6:16. doi: 10.1186/s41038-018-0115-2. eCollection 2018.

Abstract

BACKGROUND

Bacterial infection is one of the most common complications in burn, trauma, and chronic refractory wounds and is an impediment to healing. The frequent occurrence of antimicrobial-resistant bacteria due to irrational application of antibiotics increases treatment cost and mortality. Graphene oxide (GO) has been generally reported to possess high antimicrobial activity against a wide range of bacteria . In this study, a graphene oxide-quaternary ammonium salt (GO-QAS) nanocomposite was synthesized and thoroughly investigated for synergistic antibacterial activity, underlying antibacterial mechanisms and biocompatibility and .

METHODS

The GO-QAS nanocomposite was synthesized through amidation reactions of carboxylic group end-capped QAS polymers with primary amine-decorated GO to achieve high QAS loading ratios on nanosheets. Next, we investigated the antibacterial activity and biocompatibility of GO-QAS and .

RESULTS

GO-QAS exhibited synergistic antibacterial activity against bacteria through not only mechanical membrane perturbation, including wrapping, bacterial membrane insertion, and bacterial membrane perforation, but also oxidative stress induction. In addition, it was found that GO-QAS could eradicate multidrug-resistant bacteria more effectively than conventional antibiotics. The and toxicity tests indicated that GO-QAS did not exhibit obvious toxicity towards mammalian cells or organs at low concentrations. Notably, GO-QAS topically applied on infected wounds maintained highly efficient antibacterial activity and promoted infected wound healing .

CONCLUSIONS

The GO-QAS nanocomposite exhibits excellent synergistic antibacterial activity and good biocompatibility both and . The antibacterial mechanisms involve both mechanical membrane perturbation and oxidative stress induction. In addition, GO-QAS accelerated the healing process of infected wounds by promoting re-epithelialization and granulation tissue formation. Overall, the results indicated that the GO-QAS nanocomposite could be applied as a promising antimicrobial agent for infected wound management and antibacterial wound dressing synthesis.

摘要

背景

细菌感染是烧伤、创伤和慢性难愈性伤口最常见的并发症之一,也是伤口愈合的一大障碍。由于抗生素的不合理应用导致耐药菌频繁出现,增加了治疗成本和死亡率。氧化石墨烯(GO)通常被报道对多种细菌具有高抗菌活性。在本研究中,合成了氧化石墨烯 - 季铵盐(GO - QAS)纳米复合材料,并对其协同抗菌活性、潜在抗菌机制和生物相容性进行了深入研究。

方法

通过羧基封端的季铵盐聚合物与伯胺修饰的GO的酰胺化反应合成GO - QAS纳米复合材料,以在纳米片上实现高季铵盐负载率。接下来,我们研究了GO - QAS的抗菌活性和生物相容性。

结果

GO - QAS不仅通过机械性膜扰动(包括包裹、细菌膜插入和细菌膜穿孔),还通过诱导氧化应激对细菌表现出协同抗菌活性。此外,发现GO - QAS比传统抗生素更有效地根除多重耐药菌。细胞毒性和动物毒性试验表明,GO - QAS在低浓度下对哺乳动物细胞或器官未表现出明显毒性。值得注意的是,局部应用于感染伤口的GO - QAS保持了高效抗菌活性并促进了感染伤口愈合。

结论

GO - QAS纳米复合材料在体外和体内均表现出优异的协同抗菌活性和良好的生物相容性。抗菌机制包括机械性膜扰动和氧化应激诱导。此外,GO - QAS通过促进再上皮化和肉芽组织形成加速了感染伤口的愈合过程。总体而言,结果表明GO - QAS纳米复合材料可作为一种有前景的抗菌剂用于感染伤口管理和抗菌伤口敷料合成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fed0/5961493/4521476e815b/41038_2018_115_Sch1_HTML.jpg

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