Laboratory of Cell Biology, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany.
DOT GmbH, 18059 Rostock, Germany.
Biomaterials. 2015 Mar;44:36-44. doi: 10.1016/j.biomaterials.2014.12.022. Epub 2015 Jan 10.
The supply of titanium implants which are widely used in orthopaedics with both regenerative and anti-microbial properties will achieve a great progress in bone regeneration. We asked, whether by appropriate concentrations of copper ions it will be possible both to inhibit growth of bacteria and stimulate biological responses in mesenchymal stem cells (MSC). Using titanium material which released galvanically deposited copper at concentrations from 0.3 to 1.75 mM, growth of planktonic Staphylococcus aureus was blocked and more importantly adherent bacteria were cleared from the material surface within 24 h. To test biological responses of human bone marrow derived MSC due to copper ions, we found that copper stimulated the proliferation of MSC in a narrow concentration range around 0.1 mM. Similar copper concentrations enhanced osteogenic differentiation of MSC when cells were cultured in osteogenic differentiation medium. We observed increased activity of alkaline phosphatase (ALP), higher expression of collagen I, osteoprotegerin, osteopontin and finally mineralization of the cells. We conclude that titanium implants that release copper ions can be effective against bacterial infections at higher concentrations of copper near the implant surface and can promote bone regeneration when its concentration becomes lower due to diffusion.
具有再生和抗菌性能的钛植入物在骨科中的应用供应将在骨再生方面取得重大进展。我们想知道，通过适当浓度的铜离子，是否既能抑制细菌生长，又能刺激间充质干细胞（MSC）的生物反应。使用钛材料，其以 0.3 至 1.75mM 的浓度释放电沉积铜，可阻止浮游金黄色葡萄球菌的生长，更重要的是，在 24 小时内，附着在材料表面的细菌被清除。为了测试铜离子对人骨髓来源 MSC 的生物学反应，我们发现铜在 0.1mM 左右的狭窄浓度范围内刺激 MSC 的增殖。当细胞在成骨分化培养基中培养时，类似的铜浓度增强了 MSC 的成骨分化。我们观察到碱性磷酸酶（ALP）活性增加，I 型胶原、骨保护素、骨桥蛋白表达升高，最终细胞矿化。我们得出结论，释放铜离子的钛植入物在植入物表面附近较高的铜浓度下可以有效对抗细菌感染，并且由于扩散作用，当其浓度降低时，可以促进骨再生。
