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Acta Metall Sin  2017, Vol. 53 Issue (10): 1284-1302    DOI: 10.11900/0412.1961.2017.000269
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Advances in Metallic Biomaterials with both Osteogenic and Anti-Infection Properties
Xiao LIN1, Jun GE1, Shuilin WU2, Baohua LIU3, Huilin YANG1,4, Lei YANG1,4()
1 Institute of Orthopaedics, Soochow University, Suzhou 215006, China
2 School of Materials Science and Engineering, Hubei University, Wuhan 430062, China
3 Department of Basic Medical Sciences, School of Medicine, Shenzhen University, Shenzhen 518060, China
4 International Research Center for Translational Orthopaedics (IRCTO), Soochow University, Suzhou 215006, China
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Xiao LIN, Jun GE, Shuilin WU, Baohua LIU, Huilin YANG, Lei YANG. Advances in Metallic Biomaterials with both Osteogenic and Anti-Infection Properties. Acta Metall Sin, 2017, 53(10): 1284-1302.

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Abstract  

Osteogenic capacity (i.e., properties that promote new bone formation around the implant) has long been a clinical requirement for most orthopedic implants. Recently, anti-infection or antibacterial property has increasingly become critical for orthopedic implants (especially without the use of antibiotics). Orthopedic implant materials with simultaneous osteogenic and anti-infection capacities are extremely promising for orthopedic applications, but such materials are not widely available to date and have only recently been researched. In this review article, the advances in metallic biomaterials with both osteogenic and anti-infection capacities were introduced considering of the wide application of metallic biomaterials in orthopedics. Firstly, numerous attractive metal formulations that exhibit both osteogenic and anti-infection capacities as well as surface modification strategies that enhance such capacities are introduced. Secondly, several possible mechanisms underlying the osteogenic and anti-infection properties are discussed. Finally, an outlook of this field is proposed.
Key words:  metallic biomaterial      surface modification      osteogenic      anti-infection      antibacterial     
Received:  04 July 2017     
ZTFLH:  R318.08  
Fund: Supported by National Natural Science Foundation of China (Nos.81501858, 51672184 and 81622032), Jiangsu Innovation and Entrepreneurship Program and Jiangsu Provincial R&D Innovation Program (No.BY2014059-07) and the Priority Academic Program Development of Jiangsu High Education Institutions (PAPD)
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Xiao LIN
Jun GE
Shuilin WU
Baohua LIU
Huilin YANG
Lei YANG

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https://www.ams.org.cn/EN/10.11900/0412.1961.2017.000269     OR     https://www.ams.org.cn/EN/Y2017/V53/I10/1284

Material
 Composition
 Toxicity
 Biodegradability Mechanical properties
Hardness
HV		 Test
mode		 E
GPa		 YS
MPa		 US
MPa		 EL
%
Ti-Cu alloy[8,9] Ti-5%Cu
(mass fraction)		 N N 369.5 C 1247.0 1707.9 15
Ti-Nb-Ag alloy[10] Ti26Nb5Ag
(atom fraction / %)		 NA N 514 C 1240.5 5.4
Ti-Ag as cast[11,12] Ti-20Ag NA N 250 T 400 550 19
SUS 304-Cu SS[13]
 304SS containing 1.5%~5.5% Cu
(mass fraction)		 NA
 N
 240~270
 T
 570~625
Co-Cr-Mo-Cu[14]
 Co-Cr-Mo with 1%~4% Cu
(mass fraction)		 NA
 N
 274~298
 T
 310~440
 447~620
 10.7~18.5
Pure Mg
as cast[15,16]		 99.9%Mg
(mass fraction)		 Negligible Y 26 T 45 49 93 3
Mg-Ag alloy[17] Mg-2%Ag
(mass fraction)		 Negligible Y 40.1 C 44 225
Mg-Cu alloy
as cast[18]		 Mg-0.03%Cu
(mass fraction)		 N Y 32 T 80
Mg-Nd-Zn-Zr alloy[19-21] Mg-3.130Nd-
0.164Zn-0.413Zr		 Negligible Y T About 333 About 334 About 21
Zn extruded[22] 99.99%Zn
(mass fraction)		 NA Y 25 T 130 About 180 55
Zn-1Mg alloy[22] Zn-0.95%Mg
(mass fraction)		 N Y 70 T 180 250 11
Cortical bone[23] T
C		 8~12 50~130
130~190
Table 1  Novel metallic biomaterials with osteogenic and antibacterial properties[8-23]
Fig.1  Microstructures of typical metallic materials with both osteogenic and anti-infection capabilities[12,17,18]
(a) microstructure of Ti-20Ag alloy[12]
(b) microstructure of Ti-20Cu alloy [12]
(c) microstructure analysis and XRD and EDS spectra of cast Mg4Ag alloy, in which a combination of Mg4Ag and Mg54Ag17 was identified as the main phases [17]
(d) SEM image of Mg-Cu alloy showing the morphology and EDS results of the second phase [18]
Fig.2  Osteogenic and anti-infection properties of a series of Mg-Cu alloys[18]
(a) adhesion of MC3T3-E1 cells and HUVECs in different extracts
(b) ALP activity of MC3T3-E1 cells after incubation for 4, 7 and 14 d in different extracts (**p<0.01 compared to pure Mg; #p<0.05 and ##p<0.01compared to the control)
(c) colony-forming unit(CFU)/mL of S. aureus after incubation with extractions of different samples in Hank's solution for various intervals
Fig.3  Microstructures of typical surface modifications with both osteogenic and anti-infection capabilities on metallic materials[61,66,72,77]
(a) TiO2 nanotube microstructure on the silver deposited surface [61]
(b) surface morphology of the micro-arc oxidized Cu-incorporated TiO2 coatings [66]
(c) SEM image of an FHA surface[72]
(d) cross-section of Cu containing calcium silicate coating on Ti metal[77]
Fig.4  Cross-sectional (a) and top (b) morphologies of the Cu/Zn co-substituted HA coatings [96]
Agent Antibacterial mechanism Biological benefit
Ag Disrupting functions of bacteria to form a nonculturable state[139-141] Not clear
Cu
 Generation of reactive oxygen species[142];
Formation of cavities in the bacterial cell wall[143]		 Preventing osteoporosis[144,145];
Promoting osteogenic differentiation[146];
Inducing vascularization[147-149]
Zn

 Generation of reactive oxygen species[150];
Excessive uptake of Zn ions[151];
Inhibition of bacterial activities[152]		 Synthesis and stabilization of proteins[153];
Constituent of antioxidant system[154];
Anti-inflammatory effect[113];
Bone formation and vascularization[113,155,156]
Chi
 Chi/bacteria electrostatic interactions resulting in growth inhibition[157] and causing the leakage of intracellular constituents[158] Promoting growth and mineral rich matrix deposition of osteoblasts[159];
Accelerating osteogenic differentiation[122,123]
AP Disrupting the integrity of microbial membranes and subsequent cell lysis[160,161] Angiogenesis, modulation of cytokine/chemokine expression, wound healing[162,163]
Table 2  Antibacterial mechanisms and biological benefits of common antibacterial agents applied in the biomedical materials[113,122,123,139-163]
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