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异丁香酚功能化纳米凝胶在体外抑制种植体周围炎相关细菌。

Isoeugenol-functionalized nanogels inhibit peri-implantitis associated bacteria in vitro.

机构信息

Division of Oral Microbiology and Immunology, Department of Operative Dentistry, Periodontology and Preventive Dentistry, RWTH Aachen University, Aachen, Germany.

DWI-Leibniz Institute for Interactive Materials e.V., Aachen, Germany.

出版信息

Anaerobe. 2022 Jun;75:102552. doi: 10.1016/j.anaerobe.2022.102552. Epub 2022 Mar 30.

Abstract

OBJECTIVES

Obligate and facultative anaerobic bacteria adhering to dental implants are a major cause for peri-implant inflammation, which, if left untreated, can lead to implant loss. Previously, our group developed a new route for the synthesis of isoeugenol-functionalized aqueous nanogels for implant coatings.

METHODS

Here, the antimicrobial activity of several new nanogels differing in spacer length (n = 6, 9, 44), radius (60-200 nm), and amount of isoeugenol functional substance (1-20 mol%) was tested against the following peri-implantitis-associated species: Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, Escherichia coli, Actinomyces viscosus, Enterococcus faecalis, Staphylococcus aureus, Streptococcus oralis, S. parasanguinis, and the yeast Candida albicans. The minimal bactericidal concentration (MBC) and fungicidal concentration (MFC) were determined for each combination. In addition, transmission electron microscopy (TEM) and fluorescence microscopy after live-dead-staining (LD-S) were performed to visualize nanogel-microbe interactions.

RESULTS

Two nanogels, NG9-3 and NG9-4 (colloids of 80-150 nm, with a spacer length of n = 9 and feeding between 5 and 10 mol% isoeugenol), had an inhibitory effect on all Gram-positive species and on P. gingivalis and P. intermedia with MBC ≥31.25 μg/ml. TEM and LD-S images showed that cellular adhesion and uptake of nanogels resulted in swelling, shedding, or even complete detachment of the cell wall and then to bursting (see graphical abstract).

CONCLUSIONS

Functional nanogels can be used as building blocks in the design of bioactive coatings on implants to prevent infection and accelerate tissue regeneration, but the concentrations required are higher than for antibiotics.

摘要

目的

定植于牙种植体表面的专性厌氧菌和兼性厌氧菌是引发种植体周围炎的主要原因,如果不加以治疗,可能会导致种植体丧失。此前,我们小组开发了一种新方法,用于合成具有异丁香酚官能团的水基纳米凝胶,用作种植体涂层。

方法

本研究中,我们针对几种不同间隔长度(n=6、9、44)、粒径(60-200nm)和异丁香酚官能团含量(1-20mol%)的新型纳米凝胶,测试了其针对以下与种植体周围炎相关的微生物的抗菌活性:具核梭杆菌、牙龈卟啉单胞菌、中间普氏菌、伴放线放线杆菌、大肠杆菌、粘性放线菌、粪肠球菌、金黄色葡萄球菌、口腔链球菌、S.para sanguinis 和白色念珠菌。确定了每种组合的最小杀菌浓度(MBC)和杀真菌浓度(MFC)。此外,还进行了透射电子显微镜(TEM)和活/死染色(LD-S)荧光显微镜检查,以观察纳米凝胶与微生物的相互作用。

结果

两种纳米凝胶 NG9-3 和 NG9-4(粒径为 80-150nm,间隔长度 n=9,负载 5-10mol%异丁香酚)对所有革兰氏阳性菌以及牙龈卟啉单胞菌和中间普氏菌具有抑制作用,MBC≥31.25μg/ml。TEM 和 LD-S 图像显示,细胞黏附和纳米凝胶摄取导致细胞壁肿胀、脱落甚至完全分离,然后细胞破裂(见示意图)。

结论

功能纳米凝胶可用作设计具有生物活性的种植体涂层的构建块,以预防感染并加速组织再生,但所需浓度高于抗生素。

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