J Biomed Nanotechnol. 2014 Jul;10(7):1313-9. doi: 10.1166/jbn.2014.1859.
The aim of this study was to deposit simvastatin-hydroxyapatite (sim-HA) coatings on titanium surfaces by an electrochemical process and evaluate osteoprogenitor cell responses to sim-HA-coated surfaces. Simvastatin was prepared onto titanium surfaces with varying concentration (10(-7), 10(-6), 10(-5) and 10(-4) mol/L). Surface characteristics were performed by FSEM, XRD and FTIR. LC-MS/MS method was used for simvastatin quantification in Sim-HA-coated surfaces. Murine calvaria-derived pre-osteoblastic cell (MC3T3-E1) proliferation, alkaline phosphatase activity (ALP) and osteocalcin release were used to measure osteoblastic activities. FSEM observation showed rod-like HA crystals covered on all surfaces. As drug concentration increased, the crystal diameter decreased. XRD and FTIR observations showed all coatings consisted of HA. LC-MS/MS test showed the simvastatin concentration in 10(-6) mol/L group was 2.77 x 10(-7) mol/L/cm2, while in 10(-7) mol/L group was 1.89 x 10(-7) mol/L/cm2. MC3T3-E1 cells grown on 10(-7) mol/L and 10(-6) mol/L Sim-HA surfaces showed increased ALP activity as compared to HA-coated surfaces on day 7 (P < 0.05) while at 10 day, all Sim-HA groups were significantly increased than HA group (P < 0.05). Two Sim-HA groups showed significant increases in osteocalcin production on 7 10 and 14 day (P < 0.05). It showed that incubation with 10(-7) mol/L simvastatin enhanced the cell proliferation to a statistically significant extent (P < 0.05) compared with the HA group at day 7. It was concluded that simvastatin was successfully deposited into HA coatings using the electrochemical process and the sim-HA coatings enhanced differentiation of osteoprogenitor cells.
本研究旨在通过电化学方法在钛表面沉积辛伐他汀-羟基磷灰石(sim-HA)涂层,并评估成骨前体细胞对 sim-HA 涂层表面的反应。辛伐他汀以不同浓度(10(-7)、10(-6)、10(-5)和 10(-4)mol/L)制备在钛表面。通过 FSEM、XRD 和 FTIR 对表面特性进行了研究。采用 LC-MS/MS 法对 sim-HA 涂层表面的辛伐他汀进行定量。使用鼠颅骨来源的成骨前体细胞(MC3T3-E1)增殖、碱性磷酸酶活性(ALP)和骨钙素释放来衡量成骨细胞活性。FSEM 观察结果表明所有表面均覆盖有棒状 HA 晶体。随着药物浓度的增加,晶体直径减小。XRD 和 FTIR 观察结果表明所有涂层均由 HA 组成。LC-MS/MS 测试显示 10(-6)mol/L 组的辛伐他汀浓度为 2.77×10(-7)mol/L/cm2,而 10(-7)mol/L 组为 1.89×10(-7)mol/L/cm2。与 HA 涂层表面相比,MC3T3-E1 细胞在 10(-7)mol/L 和 10(-6)mol/L Sim-HA 表面上的 ALP 活性在第 7 天增加(P <0.05),而在第 10 天,所有 Sim-HA 组均明显高于 HA 组(P <0.05)。在第 7、10 和 14 天,两个 Sim-HA 组的骨钙素产量均显著增加(P <0.05)。结果表明,与 HA 组相比,在第 7 天,用 10(-7)mol/L 辛伐他汀孵育在统计学上显著增强了细胞增殖(P <0.05)。研究表明,通过电化学方法成功地将辛伐他汀沉积到 HA 涂层中,sim-HA 涂层增强了成骨前体细胞的分化。