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金属学报  2017, Vol. 53 Issue (10): 1181-1196    DOI: 10.11900/0412.1961.2017.00259
  研究论文 本期目录 | 过刊浏览 |
可降解镁基金属的生物相容性研究进展
赵颖1(), 曾利兰1, 梁涛1,2
1 中国科学院深圳先进技术研究院 深圳 518055
2 中国科学院大学 北京 100049
Development in Biocompatibility of Biodegradable Magnesium-Based Metals
Ying ZHAO1(), Lilan ZENG1, Tao LIANG1,2
1 Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
2 University of Chinese Academy of Sciences, Beijing 100049, China
引用本文:

赵颖, 曾利兰, 梁涛. 可降解镁基金属的生物相容性研究进展[J]. 金属学报, 2017, 53(10): 1181-1196.
Ying ZHAO, Lilan ZENG, Tao LIANG. Development in Biocompatibility of Biodegradable Magnesium-Based Metals[J]. Acta Metall Sin, 2017, 53(10): 1181-1196.

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摘要: 

镁基金属以其良好的生物相容性、与骨组织匹配的力学性能以及在人体内可降解吸收等特点,成为极具临床应用前景的新型生物可降解植入材料,未来有望替代传统的医用金属材料(如不锈钢、钛合金等)应用于骨科内植入器件、心血管支架等领域。本文综合评述了近年来国内外可降解镁基金属的生物相容性研究进展,从合金化和表面改性2方面对镁基金属的体内外细胞相容性、血液相容性和组织相容性等相关研究进行了介绍,并对镁基金属未来在临床上的应用和发展趋势进行了展望。
关键词 ： 镁基金属,  降解,  细胞相容性,  血液相容性,  组织相容性    
Abstract：

Magnesium-based metals become novel biodegradable implanting material and present good clinical application prospect due to their good biocompatibility, mechanical properties matching with bone tissue as well as absorbable and biodegradable properties in human body. They are expected to replace traditional medical metals such as stainless steel and titanium alloy in the area of orthopaedics and cardiovascular stent. In this paper, the current research status about the biocompatibility of magnesium based metals both at home and abroad in recent years has been reviewed. In vitro and in vivo cytocompatibility, hemocompatibility and histocompatibility have been mentioned from aspects of alloying and surface modification. The clinical application and development tendencies for magnesium based metals are also proposed.
Key words： magnesium-based metal    degradation    cytocompatibility    hemocompatibility    histocompatibility
收稿日期: 2017-06-30     
ZTFLH:  R318.08  
基金资助:国家自然科学基金项目Nos.81572113和51501218,广东省自然科学基金项目No.2014A030310129,深圳基础研究项目Nos.JCYJ20160229195249481、JCYJ20160429185449249和JCYJ20160608153641020,深港创新圈项目No.SGLH-20150213143207910及深圳市孔雀团队项目No.110811003586331
作者简介:

作者简介 赵 颖,女,1975年生,研究员,博士
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https://www.ams.org.cn/CN/10.11900/0412.1961.2017.00259      或      https://www.ams.org.cn/CN/Y2017/V53/I10/1181

Alloy Cell viability / % Hemolysis rate / %
L-929 Human primitive MC3T3-E1 HUVECs MG63
osteoblasts
Rapid solidified Mg-3Ca[9] >90
As-cast Mg-5Zn-1Ca[10] 100
As-extruded Mg-1Ca[11] >90
As-cast Mg-0.5Sr[14] >95
As-cast Mg-1Sr[19] 96.3 2.54
As-rolled pure Mg[19] 98.3 7.13
Backward extruded Mg-1Zn-0.8Sr[22] >90
As-cast Mg-1.38Si-0.5Sr-0.6Ca[23] >100
As-extruded Mg-6%Zn[29] >80
As-cast Mg-1Ca-0.5Sr-6Zn[30] >80
Sub-rapid solidified Mg-1Sn[36] >100
Sub-rapid solidified Mg-3Sn[36] >100
As-cast Mg-0.03Cu[45] >100 125
Mg-Nd-Zn-Zr[49] >75
表1  合金化对可降解镁基金属的细胞存活率和溶血率的影响[9-11,14,19,22,23,29,30,36,45,49]
Material In vitro In vivo
Corrosion Hemolysis Cytocompatibility Size Implant Corrosion rate New bone
rate rate mm duration mma-1 formation
mma-1 % (Volume loss) (Yes/No)
JDBM[55] 0.337 52.0
MgF2-coating JDBM[55] 0.253 10.1 ↓
MgF2-coated Mg-0.8Ca[56] ?2.5×25 3 weeks (8.54%) Yes
6 weeks (25.33%) Yes
LAE442[57] ?3×5 12 weeks 0.31±0.06
MgF2-coated LAE442[57] ?3×5 12 weeks 0.13±0.03
Mg-3Zn-0.8Zr[58] ?3×10 3 months (37.02%) Yes
MgF2-coated Mg-3Zn-0.8Zr[58] ?3×10 3 months (23.85%) Yes
AZ31B[59] ?2×7 3 months Yes
F-AZ31B[59] ?2×7 3 months Yes
Mg-Zn-Zr[60] 0.92 ?3.5×15 6 months 0.861±0.021 Yes
MgF2-coated Mg-Zn-Zr[60] 0.45 ↑ ?3.5×15 6 months 0.516±0.015 Yes
AZ31[61] 1.94
FAZ31[61] 1.18 ↑
Mg[62] ?4×10 4 weeks Yes
HA/MgF2-coated Mg[62] ↑ ?4×10 4 weeks Yes
表2  氟化处理对镁基金属体内外降解性能和生物相容性的影响[55-62]
Material In vitro In vivo
Hemolysis Cytocompatibility Size Implant site Implant Weight New bone
rate mm duration loss formation
% % (Yes/No)
AZ31[64] ?1×5 Rat femur 12 weeks 33 Yes
β-TCP Coating AZ31[64] ↑ ?1×5 Rat femur 12 weeks 17 Yes
JDBM [65] >70% 10×10×1 Rat subcutaneous 40 d >20
HT3#-JDBM[65] <6% ↑ 10×10×1 Rat subcutaneous 40 d <10
HT2h-Mg[66] ?2.5×10 Rabbit femur 8 weeks Yes
HT24h-Mg[66] ?2.5×10 Rabbit femur 8 weeks Yes
表3  水热处理对镁基金属体内外降解性能和生物相容性的影响[64-66]
Material Electrolyte MAO Cytocompatibility Hemolysis rate
parameter MG63 L-929 BMSCs MC3T3-E1
Mg-1Ca[67]
MAO-Mg-1Ca[67] Na2SiO3, NaOH 400 V, 10 min ↑
ZK60[68] Na2SiO39H2O, 450 V, 5 min ↑ 6.79%±2.88%
MAO-ZK60[68] KOH, KF 0.39%±0.44%
ZK60[69] 28.78%
MAO-ZK60[69] Na2SiO39H2O, 370 V, 5 min ↑ 1.04%
KOH,KF2H2O
Mg-1.0Zn-1.0Ca[70] 24.58%±1.82%
MAO-Mg-1.0Zn-1.0Ca[70] NaOH, Na4SiO4, 400 V, 5 min ↑ 2.25%±0.23%
NaF
WE42[71] 50.37%±0.42%
MAO/PLLA-WE42[71] NaOH, Na2SiO3 40 min 1.79%±0.67%
AZ31[72] 93.290%±0.782%
MAO/PLLA-AZ31[72] Na2SiO39H2O, 50 mAcm-2, 0.806%±0.771%
NaOH, NaF 15 min
AZ31[73]
PEO/PCL-AZ31[73] Na2SiO39H2O, ↑
KOH, KF2H2O 0.4 mAcm-2, 30 min
表4  微弧氧化处理医用镁基金属体外生物相容性[67-73]
图1  MgZnYNd、MgZnYNd-P、MgZnYNd-A-P、MgZnYNd-B-A-P样品与人脐静脉内皮细胞(EA.hy926)和鼠血管平滑肌细胞(VSMC)细胞共培养24 h后的NO释放量[79]
图2  纯Mg、2%-Phe-PEA-Mg、4%-Phe-PEA-Mg和2%PLGA-Mg样品与VSMC细胞间接和直接培养24 h后的NO释放量[83]
图3  MgZnYNd、 PLGA-coated MgZnYNd和 6-Arg-6 PEUU-coated MgZnYNd 的溶血率及Arg-PEUU-coated MgZnYNd、PLGA-coated和bare MgZnYNd与人脐静脉内皮细胞(HUVEC)细胞共培养24 h后的NO释放量[84]
图4  在表面制备了缺钙羟基磷灰石(Ca-def HA)涂层及无涂层的Mg-Zn-Ca合金植入8、12、18和24周的Micro-CT 2D重建结果,以及植入18和24周后的组织学结果(HE染色)[94]
图5  纯Mg、MgCP30和MgCP60 样品术后0、4、8和12周的Micro-CT结果及组织学结果[101]
图6  未离子注入AZ91和等离子注入Al和O的AZ91在手术后不同时间点的Micro-CT结果和骨量变化,术后2个月Micro-CT 3D重建结果及术后8周硬组织吉姆萨染色结果[109]
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