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Acta Metall Sin  2017, Vol. 53 Issue (10): 1181-1196    DOI: 10.11900/0412.1961.2017.00259
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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
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Ying ZHAO, Lilan ZENG, Tao LIANG. Development in Biocompatibility of Biodegradable Magnesium-Based Metals. Acta Metall Sin, 2017, 53(10): 1181-1196.

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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     
Received:  30 June 2017     
ZTFLH:  R318.08  
Fund: Supported by National Natural Science Foundation of China (Nos.81572113 and 51501218), Natural Science Foundation of Guangdong Province (No.2014A030310129), Shenzhen Science and Technology Research Funding (Nos.JCYJ20160229195249481, JCYJ20160429185449249 and JCYJ20160608153641020), Shenzhen-Hong Kong Technology Cooperation Funding Scheme (No.SGLH20150213143207910) and Shenzhen Peacock Programs (No.110811003586331)
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Ying ZHAO
Lilan ZENG
Tao LIANG

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https://www.ams.org.cn/EN/10.11900/0412.1961.2017.00259     OR     https://www.ams.org.cn/EN/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
Table 1  Cell viabilities and hemolysis rates of different mgnesium-based metals[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
Table 2  Influences of HF surface modification on degradation behavior and biocompatibility of magnesium- based metals in vitro and in vivo[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
Table 3  Influences of hydrothermal treatment on degradation behavior and biocompatibility of magnesium-based metals in vitro and in vivo[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
Table 4  In vitro evaluations of biocompatibility and hemolysis rate of MAO magnesium-based metals[67-73]
Fig.1  NO released of human umbilical vein endothelial cells (EA.hy926) (a) and rodent vascular smooth muscle cells (VSMC) (b) in the culture media for bare MgZnYNd, MgZnYNd-P, MgZnYNd-A-P and MgZnYNd-B-A-P samples (Dulbecco's modified eagle medium (DMEM) with serum worked as blank control)[79]
Fig.2  NO release from VSMC cells cultured in the extract of bare magnesium, 2%-Phe-PEA-Mg, 4%-Phe-PEA-Mg and 2%PLGA-Mg samples (indirect assay) and onto bare magnesium, 2%-Phe-PEA-Mg, 4%-Phe-PEA-Mg and 2%PLGA-Mg samples (direct assay) over a 24 h incubation period (DMEM with serum acted as a blank control)[83]
Fig.3  Hemolysis rate of bare MgZnYNd, PLGA-coated MgZnYNd, and 6-Arg-6 PEUU-coated MgZnYNd at different A/G ratios (a), NO production of human umbilical vein endothelial cell (HUVEC) cultured onto Arg-PEUU-coated MgZnYNd at different Arg to GAE feed ratios for 24 h (b) (PLGA-coated and bare MgZnYNd served as the biomaterial controls along with a DMEM- and serum-treated tissue culture plate as the blank control)[84]
Fig.4  Micro-CT 2D reconstruction images of uncoated Mg-Zn-Ca alloy and Ca-def HA coated Mg-Zn-Ca alloy after implantation of 8, 12, 18 and 24 weeks (a), histological photographs of uncoated Mg-Zn-Ca alloy and Ca-def HA coated Mg-Zn-Ca alloy after implantation of 18 and 24 weeks (HE stained) (b)[94]
Fig.5  Micro-CT images of bare Mg, MgCP30 and MgCP60 samples after 0, 4, 8, and 12 weeks post-operation (a), histological photographs of HE stained sections of the tissues around bare Mg, MgCP30 and MgCP60 after 4, 8 and 12 weeks post-operation (b)[101]
Fig.6  Micro-CT of AZ91 (a) and Al2O3-treated AZ91 (b) immediately after surgery and 1, 2, 3, 4 and 8 weeks of post-operation (Yellow arrows showed new bone formation), the percentage changes in bone volume of AZ91 and Al2O3- treated AZ91 after surgery at different times (c), Micro-CT 3D reconstruction of AZ91 and Al2O3- treated AZ91 samples after 2 months of post-operation (d), Giemsa-stained hard tissue sections of AZ91 (e) and Al2O3-treated AZ91 (f) after 8 weeks of post-operation (Black arrows indicated newly formed bones and red arrows indicated osteoblast-like cells)[109]
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