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用于预防医用植入设备感染的抗菌肽基凝胶

Antibacterial Peptide-Based Gel for Prevention of Medical Implanted-Device Infection.

作者信息

Mateescu Mihaela, Baixe Sébastien, Garnier Tony, Jierry Loic, Ball Vincent, Haikel Youssef, Metz-Boutigue Marie Hélène, Nardin Michel, Schaaf Pierre, Etienne Olivier, Lavalle Philippe

机构信息

Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche-S 1121, Biomatériaux et Bioingénierie, Strasbourg, France.

Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.

出版信息

PLoS One. 2015 Dec 14;10(12):e0145143. doi: 10.1371/journal.pone.0145143. eCollection 2015.

Abstract

Implanted medical devices are prone to infection. Designing new strategies to reduce infection and implant rejection are an important challenge for modern medicine. To this end, in the last few years many hydrogels have been designed as matrices for antimicrobial molecules destined to fight frequent infection found in moist environments like the oral cavity. In this study, two types of original hydrogels containing the antimicrobial peptide Cateslytin have been designed. The first hydrogel is based on alginate modified with catechol moieties (AC gel). The choice of these catechol functional groups which derive from mussel's catechol originates from their strong adhesion properties on various surfaces. The second type of gel we tested is a mixture of alginate catechol and thiol-terminated Pluronic (AC/PlubisSH), a polymer derived from Pluronic, a well-known biocompatible polymer. This PlubisSH polymer has been chosen for its capacity to enhance the cohesion of the composition. These two gels offer new clinical uses, as they can be injected and jellify in a few minutes. Moreover, we show these gels strongly adhere to implant surfaces and gingiva. Once gelled, they demonstrate a high level of rheological properties and stability. In particular, the dissipative energy of the (AC/PlubisSH) gel detachment reaches a high value on gingiva (10 J.m-2) and on titanium alloys (4 J.m-2), conferring a strong mechanical barrier. Moreover, the Cateslytin peptide in hydrogels exhibited potent antimicrobial activities against P. gingivalis, where a strong inhibition of bacterial metabolic activity and viability was observed, indicating reduced virulence. Gel biocompatibility tests indicate no signs of toxicity. In conclusion, these new hydrogels could be ideal candidates in the prevention and/or management of periimplant diseases.

摘要

植入式医疗设备容易受到感染。设计新的策略来减少感染和植入物排斥是现代医学面临的一项重要挑战。为此,在过去几年中,许多水凝胶被设计成抗菌分子的基质,用于对抗在口腔等潮湿环境中常见的感染。在这项研究中,设计了两种含有抗菌肽Cateslytin的新型水凝胶。第一种水凝胶基于用儿茶酚部分修饰的藻酸盐(AC凝胶)。这些源自贻贝儿茶酚的儿茶酚官能团的选择源于它们在各种表面上的强粘附特性。我们测试的第二种凝胶类型是藻酸盐儿茶酚和硫醇封端的普朗尼克(AC/PlubisSH)的混合物,普朗尼克是一种衍生自著名生物相容性聚合物普朗尼克的聚合物。选择这种PlubisSH聚合物是因为它有增强组合物内聚力的能力。这两种凝胶提供了新的临床用途,因为它们可以在几分钟内注射并凝胶化。此外,我们表明这些凝胶能牢固地粘附在植入物表面和牙龈上。一旦凝胶化,它们就表现出高水平的流变学特性和稳定性。特别是,(AC/PlubisSH)凝胶在牙龈(10 J.m-2)和钛合金(4 J.m-2)上的耗散能量达到很高的值,形成了强大的机械屏障。此外,水凝胶中的Cateslytin肽对牙龈卟啉单胞菌表现出强大的抗菌活性,观察到细菌代谢活性和活力受到强烈抑制,表明毒力降低。凝胶生物相容性测试表明没有毒性迹象。总之,这些新型水凝胶可能是预防和/或管理种植体周围疾病的理想候选材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ff/4682826/c812dc2fbba3/pone.0145143.g001.jpg

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