CN116099050A - 一种利用无机活性离子改性钛基植入物表面的方法 - Google Patents
一种利用无机活性离子改性钛基植入物表面的方法 Download PDFInfo
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Abstract
本发明提供了一种利用无机活性离子改性钛基植入物表面的方法。针对钛植入物在临床运用存在的问题，采用阳极氧化工艺生成具有一定管间距的二氧化钛纳米管后，碱热法将锶离子修饰到材料表面，光还原法将纳米银颗粒修饰至材料表面。最终制备出修饰上锶、银两种活性离子的二氧化钛纳米管，实验证实其具有促成骨活性和高效抗菌的双重功能。
Description
技术领域
本发明属于金属医用材料表面改性技术领域，具体涉及在具有管间距的二氧化钛纳米管上修饰锶、银两种活性离子。
背景技术
医用金属材料的日益成熟发展，使得医用材料逐步成为骨骼、牙齿等硬组织的替代和心血管等软组织支撑的首选材料。其中钛植入物因其更好的机械性能，优异抗腐蚀性能，更高生物相容性在临床得到大量的应用。但是仍存在骨界面结合不良引起植入物松动和植入物术后感染等问题，这些问题都可能最终导致植入物手术的失败。为解决钛植入物存在的缺陷，相关研究主要针对钛材料的表面处理，主要目的在于增加表面粗糙度以及生物活性。主要使用方法有如喷砂和喷涂、酸蚀和磁控溅射、等离子喷涂等，但存在涂层疲劳强度较低，涂层对金属基底吸附性差等问题。
阳极氧化工艺可生成附着牢固的二氧化钛纳米管，解决了其他表面处理工艺存在的涂层疲劳强度低的问题，同时生成的二氧化钛纳米管的高孔隙率和大比表面积这两个特性使得在其表面进行修饰改性更容易实现，进而解决了涂层功能单一的问题。
银作为目前公认的广谱抗菌剂，已应用于血管导管、尿管导管以及全髋关节置换术的假体以预防术后感染，具有高效的抗菌性能。纳米银颗粒可以破坏细胞膜，导致细菌结构改变的同时诱导活性氧的释放，形成具有杀菌作用的自由基。材料表面的纳米银颗粒在体内环境会被氧化释放出游离的银离子，银离子会和蛋白质以及带负电荷的核酸结合，破坏细菌的细胞壁、细胞膜和核酸的结构。纳米银独特且多重的杀菌机制使得细菌难以产生抗药性。原位还原法是一种有效而简单的制备方法，可以调节沉积银纳米粒子的数量和控制表面银纳米粒子的大小。银离子在本研究的主要作用在于解决术后感染问题，较高浓度的银离子具有优异的抗菌性能，但较高浓度的银离子具有一定的细胞毒性，因此在本发明中引入锶离子。锶离子具有高的生物活性以及优异的促成骨性能，雷奈酸锶作为抗骨质疏松剂已在临床上得到广泛使用，锶离子能够干扰 RANK/RANKL/OPG 信号通路从而抑制破骨细胞的形成，同时可以刺激成骨细胞的增殖、分化和矿物质形成，产生细胞因子 CK(cytokine)和生长因子 GFs (growth factors)刺激 MSCs 成骨分化，促进诱导 M2 巨噬细胞再生极化减少早期炎症反应。对钛基植入物进行无机活性离子的改性，通过无机活性离子将钛基植入物修饰成为具有促成骨、抗菌的多功能复合植入物材料。
发明内容
本发明的目的在于提供一种利用无机活性离子改性钛基植入物表面的方法，制备出具有优异抗菌性能的材料，同时锶的引入提高了对成骨前体细胞的生物相容性，减小了银离子的细胞毒性。
为实现上述目的，本发明采用如下技术方案：
步骤一，以纯钛片作为阳极，采用阳极氧化的方法在纯钛表面制备具有一定管间距的二氧化钛纳米管，然后在空气氛围中退火；
步骤二，获得的材料在氢氧化锶水溶液中水热处理；
步骤三，获得的材料浸泡在AgNO3水溶液中避光吸附固定，最后利用氙灯光源照射，将吸附的银离子还原为银纳米颗粒。
进一步地，阳极氧化工艺中所述阳极氧化电压为40-80 V，在40-80 °C阳极氧化1-4小时，电解液为0.1-0.4 M的NH4F和1-4 M的H2O的三乙二醇溶液；退火温度为400-500 °C，保温时间0.5-2小时，升温速率为1-3 °C/min。
进一步地，氢氧化锶水溶液浓度为0.01 M-0.03 M，水热温度为150-350 °C，水热时间为1-4小时。
进一步地，AgNO3水溶液浓度为0.005-0.8 M，吸附时间为12-16小时。
进一步地，氙灯光源光功率为95.3 mW/cm2，照射时间为0.5-2小时。
本发明的优点在于：
与现有技术相比，有一定管间距的管阵列拥有更高的比表面积，有利于后续进行表面修饰的同时更加利于细胞的黏附和成骨分化。锶的引入提高了对成骨前体细胞的生物相容性，减小了银离子的细胞毒性。 同时材料亲水性能较高，具有更好润湿性将更有利于材料上骨细胞的生长，从而有利于植入物在周围生物系统中的骨结合。
附图说明
图1为实施例1制备的TNTs的SEM图和管径统计图。
图2为本发明提供的TNTs和无间隙TiO2与MC3T3细胞共培养24 h的SEM图。
图3为本发明提供的抗菌实验结果图和抑菌环直径统计图。
图4为本发明提供的抗菌实验的SEM图。
具体实施方式
为了进一步说明本发明，以下结合实例对本发明提供的一种利用无机活性离子改性钛基植入物表面的方法。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。此外，应理解，在阅读了本发明讲授的内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1
首先将纯钛片在丙酮、无水乙醇、去离子水中依次超声10分钟，在30 mL的NH4F/H2O/TEG电解液（含0.3 M的NH4F、3 M的H2O的三乙二醇溶液）中，以金属钛为阳极，铂片为阴极，进行电化学氧化3.5 h，氧化电压为60 V，温度为60 °C；阳极氧化结束后将样品在无水乙醇中超声清洗 10 min，无水乙醇浸泡过夜后氮气流干燥；之后使用马弗炉450 °C退火1h，升温速率为 2 °C/min，退火气氛为空气，材料命名为TNTs。
实施例2
（1）制备二氧化钛纳米管
首先将纯钛片在丙酮、无水乙醇、去离子水中依次超声10分钟，在30 mL的NH4F/H2O/TEG电解液中，以钛材为阳极，铂片为阴极，进行电化学氧化3.5 h，氧化电压为60 V，温度为60 °C；阳极氧化结束后将样品在无水乙醇中超声清洗 10 min，无水乙醇浸泡过夜后氮气流干燥；之后使用马弗炉450 °C退火1 h，升温速率为 2 °C/min，退火气氛为空气。
（2）锶的修饰
将上述二氧化钛纳米管放入50 mL水热釜中，向其中加入0.02 mol/L 的 Sr(OH)2水溶液20 mL，水热温度为200 °C，水热时间为3小时，材料命名为 Sr3@TNTs。
实施例3
（1）制备二氧化钛纳米管
首先将纯钛片在丙酮、无水乙醇、去离子水中依次超声10分钟，在30 mL 的NH4F/H2O/TEG电解液中，以钛材为阳极，铂片为阴极，进行电化学氧化3.5 h，氧化电压为60 V，温度为60 °C；阳极氧化结束后将样品在无水乙醇中超声清洗 10 min，无水乙醇浸泡过夜后氮气流干燥；之后使用马弗炉450 °C退火1 h，升温速率为 2 °C/min，退火气氛为空气。
（2）银的修饰
将上述二氧化钛纳米管在0.2 mol/L的 AgNO3水溶液中避光浸泡12 h；之后在无水乙醇中，使用氙灯光源光照 1 h，光功率为 95.3 mW/cm2，照射结束后取出晾干，材料命名为Ag0.2@TNTs。
实施例4
（1）制备二氧化钛纳米管
首先将纯钛片在丙酮、无水乙醇、去离子水中依次超声10分钟，在30 mL的NH4F/H2O/TEG电解液中，以钛材为阳极，铂片为阴极，进行电化学氧化3.5 h，氧化电压为60 V，温度为60 °C；阳极氧化结束后将样品在无水乙醇中超声清洗 10 min，无水乙醇浸泡过夜后氮气流干燥；之后使用马弗炉450 °C退火1 h，升温速率为 2 °C/min，退火气氛为空气。
（2）锶的修饰
将上述二氧化钛纳米管放入50 mL水热釜中，向其中加入0.02 mol/L 的 Sr(OH)2水溶液20 mL，水热温度为200 °C，水热时间为3小时。
（3）银的修饰
将上述锶修饰的二氧化钛纳米管在0.2 mol/L的 AgNO3水溶液中避光浸泡12 h；之后在无水乙醇中，使用氙灯光源光照 1 h，光功率为 95.3 mW/cm2，照射结束后取出晾干，材料命名为Sr3Ag0.2@TNTs。
对比例1
首先将纯钛片在丙酮、无水乙醇、去离子水中依次超声10分钟，在30 mL的H2SO4/HF/H2O（含0.1 M的H2SO4、0.125 wt%的HF的水溶液）中，以金属钛为阳极，铂片为阴极，进行电化学氧化20 min，氧化电压为20 V，温度为20 °C；阳极氧化结束后将样品在无水乙醇中超声清洗 10 min，无水乙醇浸泡过夜后氮气流干燥；之后使用马弗炉450 °C退火1 h，升温速率为 2 °C/min，退火气氛为空气，材料命名为平层TiO2。
对比例2
按照实施例1的方法制备二氧化钛纳米管，不同的是，电解液为30 mL的NH4F/H2O/EG（含0.2 M的NH4F、1 M的H2O的乙二醇溶液），氧化时间为40 min，氧化电压为40 V，温度为室温，材料命名为无间隙TiO2。
对比例3
按照实施例2的方法制备锶修饰的二氧化钛纳米管，不同的是，步骤（2）中水热时间为1 h，材料命名为Sr1@TNTs。
对比例4
按照实施例3的方法制备银修饰的二氧化钛纳米管，不同的是，步骤（2）中AgNO3水溶液为0.005 mol/L，材料命名为Ag0.005@TNTs。
对比例5
按照实施例3的方法制备银修饰的二氧化钛纳米管，不同的是，步骤（2）中AgNO3水溶液为0.8 mol/L，材料命名为Ag0.8@TNTs。
对比例6
按照实施例4的方法制备锶和银修饰的二氧化钛纳米管，不同的是，步骤（2）中水热时间为1 h，材料命名为Sr1Ag0.2@TNTs。
测试例
（1）扫描电镜观察实施例1所制备二氧化钛纳米管材料外表形貌：结果见图1，实施例1制备的二氧化钛纳米管具有一定尺寸的管间距，经统计，平均孔径为150.22 nm，拥有高的比表面积，有利于后续进行表面修饰和细胞的黏附。
（2）将对比例1制备的平层TiO2材料和对比例2制备的无间隙TiO2材料分别与MC3T3细胞共培养24 h，扫描电镜观察材料外表形貌：所得结果见图2，在同一时间点，无间隙TiO2材料与平层TiO2相比，细胞粘附数量更多，形态伸展度更好。
（3）扫描电镜观察实施例2和对比例3所制备锶修饰后的样品外表形貌：结果表明，管壁和管与管的间隙有块状物体附着，Sr3@TNTs更为密集，特别表现在管与管的间隙中。
（4）扫描电镜观察实施例3、对比例4、对比例5所制备银修饰后的样品外表形貌并进行粒径统计：结果表明，总体上随着AgNO3水溶液浓度的提高，光还原制备的银纳米颗粒尺寸增大。
（5）在室温下利用接触角测量仪对实施例4所制备的锶和银修饰后的样品的接触角进行测量，使用去离子水作为介质：结果表明，实施例4所制备的材料接触角小，亲水性高。
（6）采用纸片扩散法（K-B法）对实施例和对比例所制备的锶和银修饰后的样品进行体外抗菌实验：将大肠杆菌与上述实施例和对比例在37 °C共培养12h，扫描电镜观察样品外表形貌。实验所得结果见图3和图4，钛片、二氧化钛纳米管及较低浓度的AgNO3水溶液还原的材料（对比例4）未出现明显的抑菌区但表面细菌细胞膜破裂塌陷在管底，当AgNO3浓度到达0.2 mol/L（实施例3、实施例4、对比例5、对比例6）后，大肠杆菌在初期成功黏附至材料的表面前已经被杀死，在后续的生长过程随着银离子的释放，对周围的区域产生了稳定持续的抗菌活性，产生较为明显的细菌抑制区；另外，锶的引入不会对材料的抗菌性能产生影响（实施例2、对比例3）。
（7）对实施例和对比例所制备的锶和银修饰后的样品进行细胞毒性实验，将MC3T3细胞与样品共培养，用酶标仪在450 nm波长处测定其光吸收值，在450 nm吸光度值越大表明细胞数量越多即该组实验材料的生物相容性越高。结果表明，硝酸银浓度的提升会产生更高的细胞毒性，锶离子对成骨前体细胞拥有更高的生物活性，并成功减小较高浓度银离子所产生的细胞毒性，其中，实施例4为本发明制备过的银离子和锶离子浓度最合适的材料。
Claims (5)
1.一种利用无机活性离子改性钛基植入物表面的方法，其特征在于，通过阳极氧化法制备具有一定管间距的二氧化钛纳米管，管间空隙允许高浓度离子的负载，通过调节银离子负载的浓度控制其杀菌的性能，通过锶离子的浓度调节控制其细胞相容性，最终获得表面修饰锶和银的钛基植入物；该材料的制备方法包括如下步骤：
以纯钛片作为阳极，采用阳极氧化的方法在纯钛表面制备具有一定管间距的二氧化钛纳米管，然后在空气氛围中退火；获得的材料在氢氧化锶水溶液中水热处理；获得的材料浸泡在AgNO3水溶液中避光吸附固定，最后利用氙灯光源照射，将吸附的银离子还原为银纳米颗粒，获得在钛基表面负载的无机活性离子改性后的二氧化钛纳米管。
2. 根据权利要求1中所述的一种利用无机活性离子改性钛基植入物表面的方法，其特征在于，采用阳极氧化法制备带间隙的二氧化钛纳米管，阳极氧化电压为40-80 V，在40-80°C阳极氧化1-4小时，电解液为0.1-0.4 M的NH4F和1-4 M的H2O的三乙二醇溶液；退火温度为400-500 °C，退火时间为0.5-2小时，升温速率为1-3 °C/min。
3.根据权利要求1中所述的一种利用无机活性离子改性钛基植入物表面的方法，其特征在于，所述氢氧化锶水溶液浓度为0.01 M-0.03 M，水热温度为150-350 °C，水热时间为1-4小时。
4. 根据权利要求1中所述的一种利用无机活性离子改性钛基植入物表面的方法，其特征在于，所述AgNO3水溶液浓度为0.005-0.8 M，吸附时间为12-16小时。
5.根据权利要求1中所述的一种利用无机活性离子改性钛基植入物表面的方法，其特征在于，所述氙灯光源光功率为95.3 mW/cm2，照射时间为0.5-2小时。
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