Feng Eryou, Shen Kaiwei, Lin Feitai, Lin Wentao, Zhang Tao, Zhang Yiyuan, Lin Fengfei, Yang Yun, Lin Changjian
Department of Arthrosis Surgery, Fuzhou Second Hospital Affiliated to Xiamen University, Teaching Hospital of Fujian Medical University, Fuzhou, China.
Department of Orthopaedics, Fuzhou Second Hospital Affiliated to Xiamen University, Teaching Hospital of Fujian Medical University, Fuzhou, China.
Ann Transl Med. 2020 Aug;8(16):987. doi: 10.21037/atm-20-4901.
Delivery of local drugs with a titania nanotube is an attractive approach to combat implant-related infection. Our earlier study has confirmed that nanotubes loaded with gentamicin could significantly improve the antibacterial ability. On this basis, the used andrographolide in this paper has a high antibacterial activity, which cannot only avoid the evolution of antibiotic-resistant bacteria but also has simultaneously excellent biocompatibility with osteogenic cells.
Two mg of andrographolide was loaded into titania nanotubes, which were fabricated into different diameters (50 and 100 nm) and 200 nm length by the method of lyophilization and vacuum drying. We chose a standard strain, Staphylococcus epidermidis (American Type Culture Collection 35984), and two clinical isolates, S. aureus 376 and S. epidermidis 389 to research the bacterial adhesion at 6, 12 and 24 hours and biofilm formation at 48, and 72 hours on the andrographolide-loaded nanotubes (NT-A) using the diffusion plate method. Smooth titanium (smooth Ti) and nanotubes with no drug loading (NT) were also inclusive and analyzed. Furthermore, the Sprague-Dawley (SD) rats mesenchymal stem cells were used to assess the influence of nanotubular topographies on the osteogenic differentiation of mesenchymal stem cells.
Our results showed that NT-A could inhibit bacterial adhesion and biofilm formation on implant surfaces. NT-A and NT, especially those with 100 nm diameters, were found to significantly promoted cell attachment, proliferation, diffusion, and osteogenic differentiation when compared with smooth Ti, while the same diameter in NT-A and NT did not differ.
Titania nanotube modification and andrographolide loading can significantly improve the antibacterial ability and osteogenic activity of orthopedic implants. Nanotubes-based local delivery could be a promising strategy for combating implant-associated infection.
用二氧化钛纳米管递送局部药物是对抗植入物相关感染的一种有吸引力的方法。我们早期的研究已经证实，负载庆大霉素的纳米管可以显著提高抗菌能力。在此基础上，本文中使用的穿心莲内酯具有很高的抗菌活性，不仅可以避免耐药菌的产生，同时还与成骨细胞具有优异的生物相容性。
将2mg穿心莲内酯负载到二氧化钛纳米管中，通过冻干和真空干燥的方法将其制成不同直径（50和100nm）和200nm长度的纳米管。我们选择了一株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，采用扩散平板法研究在6、12和24小时时细菌在负载穿心莲内酯的纳米管（NT-A）上的黏附情况以及在48和72小时时生物膜的形成情况。还纳入并分析了光滑钛（光滑Ti）和未负载药物的纳米管（NT）。此外，使用Sprague-Dawley（SD）大鼠间充质干细胞来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，NT-A可以抑制细菌在植入物表面的黏附和生物膜形成。与光滑Ti相比，发现NT-A和NT，尤其是直径为100nm的那些，能显著促进细胞附着、增殖、扩散和成骨分化，而NT-A和NT中相同直径的纳米管之间没有差异。
二氧化钛纳米管改性和负载穿心莲内酯可以显著提高骨科植入物的抗菌能力和成骨活性。基于纳米管的局部递送可能是对抗植入物相关感染的一种有前景的策略。
