Lin Wen-tao, Tan Hong-lue, Duan Zhao-ling, Yue Bing, Ma Rui, He Guo, Tang Ting-ting
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2014 Mar 7;9:1215-30. doi: 10.2147/IJN.S57875. eCollection 2014.
Titania nanotubes loaded with antibiotics can deliver a high concentration of antibiotics locally at a specific site, thereby providing a promising strategy to prevent implant-associated infections. In this study we have fabricated titania nanotubes with various diameters (80, 120, 160, and 200 nm) and 200 nm length via electrochemical anodization. These nanotubes were loaded with 2 mg of gentamicin using a lyophilization method and vacuum drying. A standard strain, Staphylococcus epidermidis (American Type Culture Collection 35984), and two clinical isolates, S. aureus 376 and S. epidermidis 389, were selected to investigate the anti-infective ability of the gentamicin-loaded nanotubes (NT-G). Flat titanium (FlatTi) and nanotubes with no drug loading (NT) were also investigated and compared. We found that NT-G could significantly inhibit bacterial adhesion and biofilm formation compared to FlatTi or NT, and the NT-G with 160 nm and 200 nm diameters had stronger antibacterial activity because of the extended drug release time of NT-G with larger diameters. The NT also exhibited greater antibacterial ability than the FlatTi, while nanotubes with 80 nm or 120 nm diameters had better effects. Furthermore, human marrow derived mesenchymal stem cells were used to evaluate the effect of nanotubular topographies on the osteogenic differentiation of mesenchymal stem cells. Our results showed that NT-G and NT, especially those with 80 nm diameters, significantly promoted cell attachment, proliferation, spreading, and osteogenic differentiation when compared to FlatTi, and there was no significant difference between NT-G and NT with the same diameter. Therefore, nanotube modification and gentamicin loading can significantly improve the antibacterial ability and osteogenic activity of orthopedic implants.
负载抗生素的二氧化钛纳米管可在特定部位局部递送高浓度抗生素,从而为预防植入物相关感染提供了一种有前景的策略。在本研究中,我们通过电化学阳极氧化制备了直径分别为80、120、160和200 nm且长度为200 nm的二氧化钛纳米管。采用冻干法和真空干燥法将这些纳米管负载2 mg庆大霉素。选择标准菌株表皮葡萄球菌(美国典型培养物保藏中心35984)以及两株临床分离株金黄色葡萄球菌376和表皮葡萄球菌389,以研究负载庆大霉素的纳米管(NT-G)的抗感染能力。还对平整钛片(FlatTi)和未负载药物的纳米管(NT)进行了研究和比较。我们发现,与FlatTi或NT相比,NT-G能显著抑制细菌黏附和生物膜形成,并且直径为160 nm和200 nm的NT-G由于较大直径的NT-G药物释放时间延长而具有更强的抗菌活性。NT也比FlatTi表现出更强的抗菌能力,而直径为80 nm或120 nm的纳米管效果更好。此外,使用人骨髓间充质干细胞评估纳米管形貌对间充质干细胞成骨分化的影响。我们的结果表明,与FlatTi相比,NT-G和NT,尤其是直径为80 nm的NT-G和NT,能显著促进细胞黏附、增殖、铺展和成骨分化,并且相同直径的NT-G和NT之间没有显著差异。因此,纳米管改性和负载庆大霉素可显著提高骨科植入物的抗菌能力和成骨活性。