聚醚醚酮表面改性策略研究进展
Advances in Surface Modification Strategies for Polyetheretherketone
DOI: 10.12677/ACM.2024.142612, PDF, HTML, XML, 下载: 275  浏览: 453 
作者: 徐朕钰:新疆医科大学第一附属医院(附属口腔医院)口腔修复种植科,新疆 乌鲁木齐;徐国强*:新疆医科大学第一附属医院(附属口腔医院)口腔修复种植科,新疆 乌鲁木齐;新疆维吾尔自治区口腔医学研究所,新疆 乌鲁木齐
关键词: 聚醚醚酮表面改性生物活性 Polyetheretherketone Surface Modification Bioactivity
摘要: 聚醚醚酮(polyetheretherketone, PEEK)作为一种新型医学生物材料,有希望成为金属、合金等传统骨植入物的替代品,但其作为一种疏水材料,具有化学稳定性强的特点,不利于骨结合的发生,且感染风险较大。表面改性既不会影响PEEK的机械性能,也能增加PEEK的生物活性。本文总结了PEEK表面改性方向的相关研究,从表面处理与表面涂层两个方面对PEEK的表面改性进行综述,旨在为今后的研究提供一定的参考与思路。
Abstract: Polyetheretherketone (PEEK), as a new medical biomaterial, is promising to be a substitute for tra-ditional bone implants such as metals and alloys, but as a hydrophobic material, it is chemically stable, which is unfavourable for osseointegration and has a high risk of infection. Surface modifica-tion will not affect the mechanical properties of PEEK, but also increase the bioactivity of PEEK. This paper summarizes the relevant research in the direction of surface modification of PEEK, and re-views the surface modification of PEEK from both surface treatment and surface coating, aiming to provide certain references and ideas for future research.
文章引用:徐朕钰, 徐国强. 聚醚醚酮表面改性策略研究进展[J]. 临床医学进展, 2024, 14(2): 4416-4421. https://doi.org/10.12677/ACM.2024.142612

1. 介绍

聚醚醚酮是一种新型聚合物,其有耐高温、耐腐蚀、低X射线阻射性等优点。相比于钛及其合金这种传统的金属生物医学材料,PEEK优异的力学性能,有助于减少应力屏蔽。但PEEK生物活性差,成骨效果欠佳,容易造成感染,这些缺陷均是PEEK大范围应用临床的阻碍。

近年来,聚醚醚酮的表面改性技术发展迅速,因为这种方法既能保证PEEK优异的机械性能不受影响,又能克服PEEK表面的活性低的缺点。主要的表面改性方法可以分为两大类:表面处理改性和表面涂层改性。

2. 表面处理改性

表面处理改性主要包括物理改性和化学改性。其中常用的物理改性有辐照改性、激光蚀刻、喷砂等,化学改性有酸化改性和湿化学法。

2.1. 物理改性

2.1.1. 辐照改性

常用的辐照改性的方法有等离子体处理、紫外线辐照等。辐照改性操作简单、应用广泛,可以改变材料表面结构和微观形貌,另外,物理改性可以与化学改性相结合,在PEEK表面接枝官能团,改善PEEK生物活性的同时保证PEEK化学性质不受影响。

等离子体处理用于生物医学材料表面的清洁,杀菌,提高亲水性,在PEEK表面产生官能团,提供反应位点和交联表面分子,改善PEEK的表面形貌。Zdenka Novotna [1] 等人通过利用氩等离子体对PEEK进行改性,发现体外小鼠成纤维细胞和人成骨细胞活性显著增强。等离子体改性PEEK,可以形成鳞状、树突状的纳米级别的微观表面 [2] ,增加PEEK表面的粗糙度,增强PEEK的成骨抗菌活性 [3] 。等离子体处理的改性PEEK的缺点在于,不能在PEEK上形成特定的复杂的结构,只能进行简单的表面改性处理 [4] 。

紫外线辐照改性操作简单、设备成本较低。由于紫外线辐照材料时穿透能力有限,不会改变材料本身的结构及硬度等机械性能。PEEK中含有的二苯甲酮结构,经紫外线辐照后,该基团羰基(C=O)部位的碳产生自由基,充当光引发剂的自由基的形成,实现表面功能化,增加PEEK的亲水性、生物相容性和生物活性 [5] ,有研究表明紫外线辐照后的PEEK有利于早期软组织细胞的黏附,有利于成骨细胞分化 [6] [7] 。此外,紫外线改性PEEK技术,可促进其他聚合物接枝到PEEK表面,尤其是烯烃类比较活泼的单体 [8] ,使PEEK表面的生物活性进一步增强。

2.1.2. 激光蚀刻

激光蚀刻是一种非接触的改性方法,可以通过调整脉冲数和密度等光学参数控制对改性的结构样式 [9] ,通过控制不同的波长可以影响PEEK的表面润湿性 [10] 。Huang [11] 等人采用超短脉冲激光处理PEEK表面,在试样表面形成了直径为200至600 μm的表面孔隙,深度约为50 μm左右。这些表面孔隙并不影响PEEK的机械性能,能提高PEEK的骨结合能力。MC3T3-E1的体外试验显示,与其他尺寸的孔相比,400 μm大孔上的细胞黏附和增殖更多。此外,刘红 [12] 等人研究用飞秒激光对PEEK及其复合材料进行改性,通过观察不同植入时间的材料与骨组织愈合情况、材料与骨之间的结合力大小并测量骨结合率,骨小梁数目及排列方式,得出结论:随着植入时间的延长,激光改性的PEEK复合材料比PEEK的生物活性更高,激光改性的PEEK材料的生物活性也明显大于PEEK。

2.1.3. 喷砂

喷砂处理是指用磨料颗粒(二氧化硅、氧化铝、二氧化钛等)对PEEK进行表面高速喷射,达到对PEEK表面进行粗化处理的效果,提高PEEK表面活性 [13] 。该方法简单经济,操作简便快捷,已经广泛应用于钛和钛合金的表面改性,但对于PEEK表面改性的具体参数尚不明确。经过喷砂的PEEK具有更为粗糙的表面,调节细胞行为,有效促进ALP的活性,有利于钙结节的形成 [14] 。不仅如此,喷砂后获得的粗糙表面也有利于PEEK与树脂基材料的结合,形成机械嵌合结构,有利于粘接 [15] 。

2.2. 化学改性

2.2.1. 酸化

PEEK只能与特定的强酸反应,例如硝酸、硫酸、氢氟酸,目前最普遍用于PEEK酸化的酸为98%的浓硫酸,这种磺化反应会在PEEK表面形成多孔样结构,有利于细胞黏附与增殖活动的发生。有研究表明磺化的PEEK使用水和丙酮浸泡漂洗后,其细胞ALP、Colla1和Runx2基因表达水平上调。体内实验结果表明,SD大鼠股骨的骨结合率增加。但是表面硫的残余对PEEK的生物相容性有一定影响,单纯的浸泡漂洗对于残余硫的清除效果欠佳 [16] 。使用水热法 [17] 或中和法 [18] ,去除PEEK表面残余硫的效果更为理想。

微量的氟能促进能骨髓基质细胞向成骨细胞的增殖和分化,还可以促进骨胶原和骨钙素的合成。用氢氟酸和硝酸对PEEK表面进行处理,可以促进rBMSC的贴壁增殖,使成骨基因表达上调,抑制巨噬细胞极化,下调促炎因子的表达,从而刺激成骨细胞分化 [19] 。

2.2.2. 湿化学法

湿化学表面改性的方法原理为通过还原、水解、偶联等一系列化学反应,在PEEK表面引入氨基基团、磷酸基团和羧酸基团等,起到活化PEEK的作用 [20] 。在120℃的温度下,将聚醚醚酮放入硼氢化钠/二甲基亚砜混合溶液中,24小时后可完成PEEK表面的羟基化 [21] 。羟基化后的PEEK可以负载生物活性物质,也可进行硅烷化等下一步反应。Zheng [22] 等人在PEEK-OH表面进一步进行硅烷化,在PEEK表面引入了-PO4H2、-COOH等化学官能团,实验结果表明改性后的PEEK有利于HA在其表面发生矿化,有利于MC3T3-E1的黏附、扩散和增殖。

3. 表面涂层改性

利用表面涂层对PEEK进行改性是一种常见方法,它可以赋予PEEK生物活性,改善植入物与人体软硬组织之间的相互作用。目前,许多材料被用作涂层材料,如羟基磷灰石(Hydroxyapatite, HA)、聚多巴胺(Polydopamine, PDA)和氧化石墨烯(Graphene Oxide, GO)等。

3.1. HA涂层

PEEK表面最常见的生物活性涂层是HA/PEEK涂层。在人类和动物的骨骼中,HA占69%的重量,具有优良的生物相容性和成骨诱导性。Johansson [23] 等人通过在PEEK表面涂覆纳米羟基磷灰石矿物,对术后3周和12周分别对24例兔股骨螺钉状和顶部穿孔植入物进行组织学评估。负载纳米羟基磷灰石的PEEK骨种植体在愈合位点的接触率更高,骨接触面积更大。这说明HA涂层的PEEK能显著改善骨形成性能。

在PEEK表面制备HA涂层的方法众多,其中有等离子喷涂、磁控溅射、电泳沉积等。HA涂层可诱导人体内新骨的生长,为新骨的形成提供一定的生理基础 [24] 。

3.2. 聚多巴胺涂层

多巴胺是通过氧化自聚和沉积这两个过程在基底材料形成PDA涂层,该涂层具有一定的黏附作用 [25] 。多巴胺具有的酚羟基与氨基基团均为亲水基团,因此多巴胺可用于疏水材料的表面改性。在PEEK上进行多巴胺的沉积,通常先将PEEK进行磺化处理,有利于后续多巴胺的沉积,且生成的PDA涂层可提供二次接枝平台,形成PDA复合涂层,可改性PEEK的亲水性,增加细胞粘附功能,有利于植入物的骨结合。

王娜 [26] 等人将磺化后聚醚醚酮,浸入多巴胺的碱性溶液中,形成PDA涂层,与细胞共培养后,表明PEEK表面形成PDA涂层后,促进了成骨细胞的早期黏附和增殖,提高了植入物的成骨活性。也有研究利用PDA涂层提供的二次反应平台,将其他活性因子、包含药物的微球等物质,固定在PEEK表面,形成复合涂层 [27] 。

3.3. 氧化石墨烯涂层

氧化石墨烯(graphene oxide, GO)可以通过石墨的化学剥离获得,是一种重要的石墨烯衍生物,富含含氧官能团,相比之石墨烯有更高的活性 [28] 。GO由于其优异的亲水性、表面功能性,被认为是一种有应用前景的生物材料 [29] ,同时GO具有其优异的抗菌性能 [30] ,

GO在多孔的PEEK表面的负载,即可以增加PEEK的抗菌活性,GO涂层具有良好的生物活性和生物相容性。Ouyang [31] 等人在磺化PEEK上涂覆了氧化石墨烯。经过详细的表征,PEEK对大肠杆菌显示出极好的抑制作用,且该涂层具有生物活性。Guo [32] 等人研究表明在磺化后的PEEK表面构建GO涂层,通过平板菌落计数实验和SEM分析得出实验组中细菌数量的显著减少,通过RT-PCR检测发现,该涂层降低了对P.g中Fim和变形链球菌中Gtf基因的相对表达。

4. 小结

聚醚醚酮的表面改性策略能对PEEK表面进行活化,近年来取得了巨大的进展,尤其是物理改性、化学改性以及表面涂层技术,但这些方法的生物安全性以及改性效果的长期稳定性,仍缺乏实验数据的支持,是PEEK表面改性技术广泛应用于临床的一项挑战。

NOTES

*通讯作者。

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