Sörensen Jan Henrik, Lilja Mirjam, Sörensen Torben Christian, Åstrand Maria, Procter Philip, Fuchs Sabine, Strømme Maria, Steckel Hartwig
Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, 24118, Kiel, Germany.
J Biomed Mater Res B Appl Biomater. 2014 Oct;102(7):1381-92. doi: 10.1002/jbm.b.33117. Epub 2014 Feb 17.
The present study investigates the use of nanoporous, biomimetic hydroxyapatite (HA) coatings deposited on TiO₂ coated fixation pins as functional implant surfaces for the local release of Tobramycin in order to prevent bacterial colonization. The impact of HA-coating thickness, coating morphology and biomechanical forces during insertion into synthetic bone on the drug loading and release properties are analyzed. The coatings are shown to exhibit bactericidal effects against Staphylococcus aureus in agar medium for a duration of 6 days after loading by adsorption with Tobramycin for only 5 min at elevated temperature and pressure. Furthermore, high performance liquid chromatography analysis shows a drug release in phosphate buffered saline for 8 days with antibiotic concentration remaining above the minimal inhibitory concentration for S. aureus during the entire release period. Biomechanical insertion tests into synthetic bone and conventional scratch testing demonstrate adhesive strength at the HA/TiO₂ interface. Biocompatibility is verified by cell viability tests. Outgrowth endothelial cells, as well as primary osteoblasts, are viable and firmly attached to both HA and TiO₂ surfaces. The results presented are encouraging and support the concept of functional HA coatings as local drug delivery vehicles for biomedical applications to treat as well as to prevent post-surgical infections.
本研究调查了沉积在二氧化钛涂层固定针上的纳米多孔仿生羟基磷灰石（HA）涂层作为功能性植入物表面用于妥布霉素局部释放以防止细菌定植的情况。分析了HA涂层厚度、涂层形态以及插入合成骨过程中的生物力学力对药物负载和释放特性的影响。通过在高温高压下仅用妥布霉素吸附5分钟加载后，这些涂层在琼脂培养基中对金黄色葡萄球菌显示出6天的杀菌效果。此外，高效液相色谱分析表明，在磷酸盐缓冲盐水中药物释放8天，在整个释放期间抗生素浓度保持在高于金黄色葡萄球菌最小抑菌浓度的水平。对合成骨进行的生物力学插入测试和传统划痕测试证明了HA/TiO₂界面处的粘附强度。通过细胞活力测试验证了生物相容性。生长的内皮细胞以及原代成骨细胞都具有活力，并牢固地附着在HA和TiO₂表面。所呈现的结果令人鼓舞，并支持了功能性HA涂层作为用于生物医学应用以治疗和预防术后感染的局部药物递送载体的概念。
