高生物活性聚醚醚酮化学改性研究进展

doi:10.16085/j.issn.1000-6613.2023-0500

摘要/Abstract

摘要：

由于聚醚醚酮（PEEK）表面疏水及生物惰性，用作骨科材料难以与周围细胞、骨组织结合。通过化学改性在PEEK分子链中引入具有生物活性的功能化基团是提高其表面细胞黏附、增殖和成骨分化能力最有效的方式。基于功能化基团引入位置的不同，本文将PEEK化学改性分为苯环位改性、酮基位改性和共聚改性等三种，并且重点综述了这些不同化学改性方法的原理和特性及其对PEEK材料生物活性的影响。苯环位改性主要是通过强酸处理引入羧基等官能团，但会残留含硫或含硝化合物，对细胞有一定的毒害作用；酮基位改性是通过胺类、硼氢化钠等试剂与酮基反应，进一步接枝引入功能化基团，但是会破坏PEEK主链上的醚酮比，影响物理性能和热性能。通过亲电、亲核及卤代改性等共聚方式在PEEK侧链引入功能化基团，能保持聚合物主链醚酮比基本不变，同时提升材料生物活性，具有良好的应用前景。在化学改性的基础上，研究多种功能基团的协同作用，进一步引入物理改性，优化面向不同场景的综合性能，是拓宽其在医疗领域应用的发展趋势。

关键词: 聚醚醚酮, 化学改性, 共聚改性, 功能化改性, 生物活性

Abstract:

Because of its hydrophobicity and biological inertness, polyether ether ketone (PEEK) used as an orthopedic material is difficult to bond with surrounding cells and bone tissues. It is the most effective method to improve cell adhesion, proliferation and osteogenic differentiation on the surface of PEEK materials by introducing biologically active groups into the molecular chain of PEEK. Based on the different introduction positions of functional groups, the chemical modification of PEEK is classified into three types: benzene cyclic modification, ketone modification and copolymerization modification. The principles and characteristics of these different chemical modification methods and their impact on the biological activity of PEEK materials are emphatically reviewed. The benzene cyclic modification mainly involved the introduction of functional groups such as carboxyl groups through strong acid treatment, resulting in the residual sulfur or nitrate compounds that has a certain toxic effect on cells. Ketone group modification used reagents such as amines and sodium borohydride to react with the ketone group and further introduced functional groups through grafting, however, it would destroy the ether-ketone ratio on the main chain of PEEK, affecting its physical and thermal properties. Introducing bioactive functional groups into the side chain of PEEK by copolymerization methods such as electrophilic addition, nucleophilic addition or halogenation-modification can maintain the ether and ketone ratio in the polymer backbone and improve the bioactivity, which has good application prospects. On the basis of chemical modification, studying the synergistic effect of various functional groups and further introducing physical modification to optimize comprehensive performance for different scenarios is the development trend for expanding the application of PEEK in the medical field.

Key words: polyether ether ketone, chemical modification, copolymerization modification, functional modification, biological activity

中图分类号:

TQ316.33

陈俊俊, 费昌恩, 段金汤, 顾雪萍, 冯连芳, 张才亮. 高生物活性聚醚醚酮化学改性研究进展[J]. 化工进展, 2023, 42(8): 4015-4028.

CHEN Junjun, FEI Chang’en, DUAN Jintang, GU Xueping, FENG Lianfang, ZHANG Cailiang. Research progress on chemical modification of polyether ether ketone for the high bioactivity[J]. Chemical Industry and Engineering Progress, 2023, 42(8): 4015-4028.

图/表 28

图1 PEEK苯环位改性示意图X为—SO3H、—NO3、—COCH3

图2 PEEK磺化程度与反应温度和反应时间的关系[18]

图3 水热处理条件对磺化PEEK中硫质量分数的影响[22]

图4 气态SO3磺化制备表面多孔PEEK植入物及其生物活性[23]

图5 硝化PEEK的结构式[25]

图6 细胞在PEEK/CF复合材料上培养1天、4天和7天后的扫描电子显微镜图[26]

图7 强酸处理前后PEEK表面的扫描电子显微镜图[27]

图8 不同浓硝酸/浓硫酸比例改性PEEK后的扫描电子显微镜图[28]

图9 未处理PEEK（Bare-PEEK）、氢氟酸处理PEEK（PEEK-AF）、硝酸处理PEEK（PEEK-AN）和混合酸处理PEEK（PEEK-AFN）样品表面在低倍和高倍下的扫描电子显微镜图[29]

图10 细胞在Bare-PEEK、PEEK-AF、PEEK-AN和PEEK-AFN上培养不同天数后的ALP和茜素红染色图[29]

图11 PEEK乙酰化及功能化改性的反应式[31]

表1 PEEK、PEEK-COOH和HOOC-PEEK-NH2和模拟体液进行脱细胞体外试验7天、15天和30天的结果[31]

聚合物	初始干重/g	湿重/g	湿重变化质量分数/%	干重/g	干重变化质量分数/%	天数
PEEK	0.132	0.142	+7.6	0.136	+3.0	7
		0.151	+14.4	0.139	+5.3	15
		0.192	+45.5	0.147	+11.4	30
PEEK-COOH	0.114	0.123	+7.9	0.118	+3.5	7
		0.132	+15.8	0.121	+6.1	15
		0.167	+46.5	0.129	+13.2	30
HOOC-PEEK-NH₂	0.086	0.093	+8.2	0.089	+3.5	7
		0.100	+16.3	0.092	+7.0	15
		0.126	+46.5	0.098	+14.0	30

图12 2，2-二苯基乙胺与PEEK反应式[33]

图13 PEEK、SNPEEK、SNPEEK-NH2上培养骨髓基质干细胞RUNX2和AKP的表达结果[28]

图14 硼氢化钠对PEEK羟基化改性机理[34]

图15 PEEK和PEEK-OH的XPS谱图[35]

图16 PEEK和碳纤维增强PEEK（CFR-PEEK）接枝PMPC的制备示意图[37]

图17 PEEK接枝PVPA制备磷酸化PEEK机理及示意图[38]

图18 PEEK和PEPA种植体植入12周后，甲苯胺蓝品红素染色种植体周围的硬组织切片骨接触分析[38]

图19 PEEK表面的酮基还原（A）、硅氧烷层的形成（B）、羧基化（C）、羟基化（D）和磷酸化（E）反应过程[40]

图20 小鼠胚胎成骨细胞前体细胞（MC3T3-E1）在P-PEEK和硅氧烷化后官能团改性PEEK上细胞黏附和增殖[41]

图21 羧基改性PEEK的合成（x=y+m+p）[43]

图22 基于4C-PH单体的PAEK-COOH合成路径[46]

图23 PEEK与PEEK-COOH表面MG63细胞增殖情况（CCK8检测od值与细胞数量成正比）[47]

图24 含甲基PEEK的合成[50]

图25 PEEK-CH3溴化反应式（n=x+y+z）[54]

图26 PEEK-COOH的制备及功能化反应式[53]

图27 PEEK-CH2Br功能化反应式[54]

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