Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis
Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis
复制标题
将依诺沙星共价固定到钛植入物表面以抑制多种细菌感染和体内耐甲氧西林金黄色葡萄球菌感染预防
DOI：
10.1128/aac.01766-16
复制
发表时间：
2017-01-01
影响因子：
4.9
通讯作者：
Yue, Bing
中科院分区：
文献类型：
--
作者：
Nie, Bin'en;Long, Teng;Yue, Bing
摘要感染是钛种植体植入失败的重要原因之一。一种正在开发的预防方法包括将抗生素，特别是万古霉素固定在钛植入物的表面上。然而，由于抗生素的特异性，这些方法在抑制多种细菌感染方面的效果有限。在目前的研究中，依诺沙星共价键合到胺功能化的钛表面通过使用聚乙二醇（PEG）间隔，并在体外和体内的杀菌效果进行了研究。用3-氨丙基三乙氧基硅烷（APTES）对钛表面进行胺官能化，通过胺官能化将PEG间隔分子共价固定在钛表面，然后将依诺沙星共价结合到PEG上，X射线光电子能谱（XPS）证实了这一点。采用涂布平板法、激光共聚焦扫描显微镜（CLSM）和扫描电子显微镜（SEM）对抗菌活性进行了表征。在体内研究中，将钛植入物接种耐甲氧西林金黄色葡萄球菌（MRSA）并植入大鼠的股骨髓腔。术后3周，通过X线摄影、显微计算机断层扫描和粘附细菌计数测定来评估感染程度。我们的数据表明，依诺沙星改性的聚乙二醇化钛表面有效地防止细菌定植，而不损害细胞活力，粘附，或在体外增殖。此外，它还可防止体内钛植入物的MRSA感染。综上所述，我们的结果表明，使用依诺沙星改性的钛是一种潜在的方法，以减轻感染的钛植入物的多种细菌物种。
ABSTRACT Infection is one of the most important causes of titanium implant failure in vivo. A developing prophylactic method involves the immobilization of antibiotics, especially vancomycin, onto the surface of the titanium implant. However, these methods have a limited effect in curbing multiple bacterial infections due to antibiotic specificity. In the current study, enoxacin was covalently bound to an amine-functionalized Ti surface by use of a polyethylene glycol (PEG) spacer, and the bactericidal effectiveness was investigated in vitro and in vivo. The titanium surface was amine functionalized with 3-aminopropyltriethoxysilane (APTES), through which PEG spacer molecules were covalently immobilized onto the titanium, and then the enoxacin was covalently bound to the PEG, which was confirmed by X-ray photoelectron spectrometry (XPS). A spread plate assay, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM) were used to characterize the antimicrobial activity. For the in vivo study, Ti implants were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and implanted into the femoral medullary cavity of rats. The degree of infection was assessed by radiography, micro-computed tomography, and determination of the counts of adherent bacteria 3 weeks after surgery. Our data demonstrate that the enoxacin-modified PEGylated Ti surface effectively prevented bacterial colonization without compromising cell viability, adhesion, or proliferation in vitro. Furthermore, it prevented MRSA infection of the Ti implants in vivo. Taken together, our results demonstrate that the use of enoxacin-modified Ti is a potential approach to the alleviation of infections of Ti implants by multiple bacterial species.