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利用可聚合万古霉素衍生物抑制表皮葡萄球菌生物膜。

Inhibition of Staphylococcus epidermidis biofilms using polymerizable vancomycin derivatives.

机构信息

Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA.

出版信息

Clin Orthop Relat Res. 2010 Aug;468(8):2081-91. doi: 10.1007/s11999-010-1266-z.

Abstract

BACKGROUND

Biofilm formation on indwelling medical devices is a ubiquitous problem causing considerable patient morbidity and mortality. In orthopaedic surgery, this problem is exacerbated by the large number and variety of material types that are implanted. Metallic hardware in conjunction with polymethylmethacrylate (PMMA) bone cement is commonly used.

QUESTIONS/PURPOSES: We asked whether polymerizable derivatives of vancomycin might be useful to (1) surface modify Ti-6Al-4V alloy and to surface/bulk modify PMMA bone cement to prevent Staphylococcus epidermidis biofilm formation and (2) whether the process altered the compressive modulus, yield strength, resilience, and/or fracture strength of cement copolymers.

METHODS

A Ti-6Al-4V alloy was silanized with methacryloxypropyltrimethoxysilane in preparation for subsequent polymer attachment. Surfaces were then coated with polymers formed from PEG(375)-acrylate or a vancomycin-PEG(3400)-PEG(375)-acrylate copolymer. PMMA was loaded with various species, including vancomycin and several polymerizable vancomycin derivatives. To assess antibiofilm properties of these materials, initial bacterial adherence to coated Ti-6Al-4V was determined by scanning electron microscopy (SEM). Biofilm dry mass was determined on PMMA coupons; the compressive mechanical properties were also determined.

RESULTS

SEM showed the vancomycin-PEG(3400)-acrylate-type surface reduced adherent bacteria numbers by approximately fourfold when compared with PEG(375)-acrylate alone. Vancomycin-loading reduced all mechanical properties tested; in contrast, loading a vancomycin-acrylamide derivative restored these deficits but demonstrated no antibiofilm properties. A polymerizable, PEGylated vancomycin derivative reduced biofilm attachment but resulted in inferior cement mechanical properties.

CLINICAL RELEVANCE

The approaches presented here may offer new strategies for developing biofilm-resistant orthopaedic materials. Specifically, polymerizable derivatives of traditional antibiotics may allow for direct polymerization into existing materials such as PMMA bone cement while minimizing mechanical property compromise. Questions remain regarding ideal monomer structure(s) that confer biologic and mechanical benefits.

摘要

背景

留置医疗器械上生物膜的形成是一个普遍存在的问题,给患者带来了相当大的发病率和死亡率。在骨科手术中,由于植入的材料种类繁多,这个问题更加严重。金属硬件与聚甲基丙烯酸甲酯(PMMA)骨水泥一起使用。

问题/目的:我们想知道万古霉素的聚合衍生物是否可以(1)对 Ti-6Al-4V 合金进行表面改性,并对 PMMA 骨水泥进行表面/体相改性,以防止表皮葡萄球菌生物膜的形成,以及(2)该过程是否改变了水泥共聚物的压缩模量、屈服强度、弹性和/或断裂强度。

方法

Ti-6Al-4V 合金用甲氧基丙基三甲氧基硅烷硅烷化,为后续的聚合物附着做准备。然后,用聚乙二醇(375)-丙烯酰胺或万古霉素-聚乙二醇(3400)-聚乙二醇(375)-丙烯酰胺共聚物形成的聚合物对表面进行涂覆。PMMA 中载入了各种物质,包括万古霉素和几种可聚合的万古霉素衍生物。为了评估这些材料的抗生物膜特性,通过扫描电子显微镜(SEM)来确定涂层 Ti-6Al-4V 上初始细菌的附着。通过 PMMA 小方测定生物膜的干质量;还测定了压缩力学性能。

结果

SEM 显示,与单独使用聚乙二醇(375)-丙烯酰胺相比,万古霉素-聚乙二醇(3400)-聚乙二醇(375)-丙烯酰胺型表面使附着的细菌数量减少了约四倍。万古霉素负载降低了所有测试的力学性能;相比之下,载入万古霉素-丙烯酰胺衍生物可以恢复这些缺陷,但没有抗生物膜特性。可聚合的聚乙二醇化万古霉素衍生物减少了生物膜的附着,但导致水泥力学性能下降。

临床相关性

本文提出的方法可能为开发抗生物膜的骨科材料提供新的策略。具体来说,传统抗生素的聚合衍生物可以直接聚合到现有的材料中,如 PMMA 骨水泥,同时最小化力学性能的损失。关于赋予生物学和机械学优势的理想单体结构仍存在疑问。

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