CN113101414A - 一种具有抗感染功能的人工关节假体 - Google Patents

一种具有抗感染功能的人工关节假体 Download PDF

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CN113101414A
CN113101414A CN202110290899.5A CN202110290899A CN113101414A CN 113101414 A CN113101414 A CN 113101414A CN 202110290899 A CN202110290899 A CN 202110290899A CN 113101414 A CN113101414 A CN 113101414A
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artificial joint
joint prosthesis
infection
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solution
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曹永平
夏丹丹
杨威
陈力建
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Changshu Zhongke Century Biotechnology Co ltd
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Abstract

一种具有抗感染功能的人工关节假体,它是通过以下方法制备得到的:(1)人工关节假体表面处理:将人工关节假体表面打磨光滑,然后经丙酮、乙醇和去离子水超声清洗后干燥,待用;(2)人工关节假体表面银离子注入或沉积:利用磁控溅射方式在人工关节表面进行银离子沉积;(3)聚多巴胺涂层的沉积:先配制Tris‑HCl缓冲液,向其中加入盐酸多巴胺溶液,完成多巴胺溶液的配制,将含银膜层的人工关节假体置于多巴胺溶液中,避光反应,在含有银离子的人工关节表面沉积聚多巴胺涂层;并通过808 nm近红外光源进行照射产生光热效应的方法,在体内释放产生的银离子和近红外光产生的局部高温具有优异的协同杀菌效果,能够减少感染的发生并增强人工关节的抗感染能力。

Description

一种具有抗感染功能的人工关节假体
技术领域
本发明涉及一种具有抗感染功能的人工关节假体,属于医疗器械表面抗感染技术领域。具体涉及一种通过光控抗菌的人工关节假体,可以减少感染的发生,并能在感染发生后快速高效地去除生物膜。
背景技术
随着世界人口老龄化程度的加剧、参加剧烈运动导致骨组织受损的人越来越多,以及人们对生活质量要求的提高,使得骨科植入物的需求逐年增加。但在人工关节植入人体后,时常发生植入失败的现象,感染的发生是导致失败的一个很重要原因。假体周围感染是人工关节植入手术的一个严重并发症,可导致手术的彻底失败,从而不得不进行二次手术。这些加大了患者的痛苦及经济压力,严重的会导致截肢甚至死亡。
对于人工关节感染问题,目前比较常用的处理措施包括抗生素全身给药和二次手术。但抗生素全身给药效率低,且对人体毒副作用大。而二次手术一方面加大了患者的痛苦及经济压力,另一方面二次手术的感染风险更大。
研发具备抗感染功能的人工关节假体是降低人工关节植入手术并发症、确保人工关节假体在体内持续稳定的有效途径。银在几千年前就已经被用作杀菌剂。自波斯时期,银就被用做容器来给水杀菌或保存食物。同时与其它金属相比,银离子具备更强的抗菌性能。其能杀死几乎所有的细菌、病毒和真菌等微生物,且在合适浓度范围内对人体细胞无害。目前各种含银的抗菌医疗器械已经在临床上得到了应用,如导尿管、人工血管、伤口敷料等。因此,在人工关节假体表面负载银,可望赋予人工关节假体抗菌能力。
为了保证银离子处于对人体细胞无害的浓度范围,需要采用膜层对离子的释放进行控制。此外,低浓度的银离子难以起到有效的杀菌效果,因此需要选用其它抗菌策略与银离子进行协同杀菌。
发明内容
发明目的:针对现有人工关节假体存在的上述不足之处,本发明的目的是提供一种具有抗感染功能的人工关节假体,一种银/聚多巴胺改性的人工关节,所述人工关节表面含有银离子,所述银离子通过物理方法注入或沉积在人工关节表面,在所述含有银离子的人工关节表面沉积有聚多巴胺涂层。通过在人工关节表面制备具有银和聚多巴胺的膜层,利用释放的银离子和聚多巴胺在近红外光照下产生的局部高温达到高效的抗菌效果,提高人工关节假体的抗感染能力,且制备工艺简单,成本低。
技术方案,为实现以上目的,本发明采用以下技术方案:
一种具有抗感染功能的人工关节假体,它是通过以下方法制备得到的:
(1)人工关节假体表面处理:将人工关节假体表面打磨光滑,然后经丙酮、乙醇和去离子水超声清洗后干燥,待用;
(2)人工关节假体表面银离子注入或沉积:利用磁控溅射方式在人工关节表面进行银离子沉积;
(3)聚多巴胺涂层的沉积:先配制Tris-HCl缓冲液,向其中加入盐酸多巴胺溶液,完成多巴胺溶液的配制,将含银膜层的人工关节假体置于多巴胺溶液中,避光反应,在含有银离子的人工关节表面沉积聚多巴胺涂层;
(4)使用去离子水对假体进行润洗,并自然烘干。
作为优选方案,以上所述的一种具有抗感染功能的人工关节假体,所述的人工关节是纯钛或钛合金的任意人工关节。
作为优选方案,以上所述的一种具有抗感染功能的人工关节假体,步骤(2)磁控溅射的真空度5~7×10-6 Pa,成膜速度为30~35nm/min;银离子沉积厚度为0.1-1μm。
作为优选方案,以上所述的一种具有抗感染功能的人工关节假体,步骤(3):先配制pH为8.5的10 mM Tris-HCl缓冲液,向其中加入2 mg/mL的盐酸多巴胺溶液,完成多巴胺溶液的配制,将含银膜层的人工关节假体置于多巴胺溶液中,避光反应6-24 h,在含有银离子的人工关节表面沉积聚多巴胺涂层。
作为优选方案,以上所述的一种具有抗感染功能的人工关节假体,步骤(3):沉积聚多巴胺涂层的厚度0.1-20μm;步骤(3)避光反应时间为6-16 h。
作为优选方案,以上所述的一种具有抗感染功能的人工关节假体,将人工关节假体在近红外808 nm激光照射下,在光热与光动力协同消除人工关节假体表面细菌生物膜感染。
有益效果是:
1. 本发明通过大量实验发现:由于聚多巴胺是一种能够粘附在几乎所以无机和有机材料表面的物质,且具有很强的结合力。其结构中氨基的存在使得其具有一定的pH响应特性,从而能够控制人工假体表面银离子的pH响应释放速率。由于细菌的出现能够产生酸性物质,使局部环境酸化。因此当细菌出现时,能够激发聚多巴胺涂层的pH响应反应,加大银离子的释放量,从而产生更有效的抗菌效果。
2. 本发明所述膜层可以通过改变多巴胺聚合时间调节聚多巴胺涂层的最佳厚度。其一方面能够调节银离子的释放速率,另一方面能够调节聚多巴胺光热效应产生的局部温度能够破坏细菌的膜结构,从而使得释放出的银离子更容易进入到细菌体内,产生细菌内局部高浓度的银离子,导致更有效的杀菌效果,有效的调节人工关节的抗菌效率。
3. 本发明所制备的人工关节假体,在近红外808 nm激光照射下,在光热与光动力协同消除人工关节假体表面细菌生物膜感染。通过光照可以快速杀菌,并储存活性氧(ROS),利用活性氧增加细菌对温度的敏感性。在无光照的情况下,缓慢释放ROS,能够抑制细菌的生长。
4. 当感染发生后,通过近红外快速照射,可以快速杀灭如人工心脏瓣膜等人工关节表面的细菌,并能高效及安全的消除生物膜。从而避免开胸手术将生物瓣膜的取出,减少给患者带来的创伤。
5. 人本发明创造性的将工关节表面银离子和聚多巴胺膜层的构建,将为人工关节抗感染提供一条新的简单有效的途径。该膜层能够利用释放的银离子以及聚多巴胺涂层光热效应产生的高温进行协同抗菌,从而达到优异的抗菌性能。该膜层将能够有效的解决人工关节植入后面临的细菌感染问题,有利于假体在体内的长期稳定存在。
6. 本发明的技术可避免使用抗生素产生耐药性,可避免抗菌剂的组织毒性,具有良好的临床应用前景。
附图说明
图1 表面磁控溅射银离子和覆聚多巴胺膜层的钛合金片抗菌效果,a为表面磁控溅射银离子和聚多巴胺膜层的钛合金片, b为钛合金片。
图2 表面磁控溅射银离子和覆聚多巴胺膜层的钛合金片表面细菌生物膜的扫描电镜图,a为表面磁控溅射银离子和聚多巴胺膜层的钛合金片, b. 钛合金片。
具体实施方式
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。
实施例1
一种具有抗感染功能的人工关节假体,它是通过以下方法制备得到的:
(1)人工关节表面处理:将Ti-6Al-4V合金材料的人工关节表面打磨光滑,经丙酮、乙醇和去离子水超声清洗后干燥待用;
(2)人工关节表面银离子注入或沉积:利用磁控溅射方式(磁控溅射的具体参数为真空度6.6×10-6 Pa,在人工关节表面进行银离子沉积,沉积厚度在0.5μm。
(3)在上述含银膜层上沉积聚多巴胺涂层:配制pH为8.5的10 mM Tris-HCl缓冲液,向其中加入2 mg/mL的盐酸多巴胺溶液,完成多巴胺溶液的配制。将人工关节置于多巴胺溶液中12 h,避光反应,完成假体表面聚多巴胺涂层的制备;
(4)使用去离子水对假体进行润洗,并自然烘干。
本发明提供的人工关节假体,当人工关节假体感染发生时,使用近红外808 nm激光光源探头照射感染发生的部位,进行激光照射,以达到快速杀灭细菌,去除人工关节假体生物膜的目的。
实施例2 抗成纤维细胞繁殖的对比实验
本发明分别进行覆银离子和聚多巴胺膜层钛合金片、磁控溅射银离子钛合金片、钛合金片和正常培养皿上进行成纤维细胞培养的实验,检测得到的OD值和不同表面成纤维细胞的相对增值率结果如下:
1、成纤维细胞培养24h的OD值的检测,具体实验结果如表1所示:
表1 成纤维细胞培养24h的OD值
钛合金片覆银离子和聚多巴胺膜层 磁控溅射银离子钛合金片 钛合金片 正常细胞组
OD值 2.021±0.011 2.314±0.018 2.891±0.088 3.037±0.482
2、对成纤维细胞的相对增值率,具体实验结果如表2所示:
表2 对成纤维细胞的相对增值率
钛合金片覆银离子和聚多巴胺膜层 钛合金片磁控溅射银离子 钛合金片
细胞相对增值率 67% 76% 95%
由表1和表2和图1和图2的实验结果表明,本发明在钛合金片表面磁控溅射银离子和覆聚多巴胺膜层后可明显增加成纤维细胞的繁殖,显示出很好的抗菌作用。
可以理解的是,以上关于本发明的具体描述,仅用于说明本发明而并非受限于本发明实施例所描述的技术方案,本领域的普通技术人员应当理解,仍然可以对本发明进行局部修改或等同替换,以达到相同的技术效果;只要满足使用需要,都在本发明的保护范围之内。

Claims (6)

1.一种具有抗感染功能的人工关节假体,其特征在于,它是通过以下方法制备得到的:
(1)人工关节假体表面处理:将人工关节假体表面打磨光滑,然后经丙酮、乙醇和去离子水超声清洗后干燥,待用;
(2)人工关节假体表面银离子注入或沉积:利用磁控溅射方式在人工关节表面进行银离子沉积;
(3)聚多巴胺涂层的沉积:先配制Tris-HCl缓冲液,向其中加入盐酸多巴胺溶液,完成多巴胺溶液的配制,将含银膜层的人工关节假体置于多巴胺溶液中,避光反应,在含有银离子的人工关节表面沉积聚多巴胺涂层;
(4)使用去离子水对假体进行润洗,并自然烘干。
2.根据权利要求1所述的一种具有抗感染功能的人工关节假体,其特征在于,所述的人工关节是纯钛或钛合金的任意人工关节。
3.根据权利要求1所述的一种具有抗感染功能的人工关节假体,其特征在于,步骤(2)磁控溅射的真空度5~7×10-6 Pa,,成膜速度为30~35nm/min;银离子沉积厚度为0.1-1μm。
4.根据权利要求1所述的一种具有抗感染功能的人工关节假体,其特征在于,步骤(3):先配制pH为8.5的10 mM Tris-HCl缓冲液,向其中加入2 mg/mL的盐酸多巴胺溶液,完成多巴胺溶液的配制,将含银膜层的人工关节假体置于多巴胺溶液中,避光反应6-24 h,在含有银离子的人工关节表面沉积聚多巴胺涂层。
5.根据权利要求1所述的一种具有抗感染功能的人工关节假体,其特征在于,步骤(3):沉积聚多巴胺涂层的厚度0.1-20μm;步骤(3)避光反应时间为6-16 h。
6.根据权利要求1~5任一项所述的一种具有抗感染功能的人工关节假体,其特征在于,将人工关节假体在近红外808 nm激光照射下,在光热与光动力协同消除人工关节假体表面细菌生物膜感染。
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