Table of Contents

Cover

Title Page

Preface

About the Authors

Chapter 1: Introduction

1.1 Traditional Metallic Biomaterials
1.2 Revolutionizing Metallic Biomaterials and Their New Biofunctions
1.3 Technical Consideration on Alloying Design of Revolutionizing Metallic Biomaterials
1.4 Novel Process Technologies for Revolutionizing Metallic Biomaterials
References

Chapter 2: Introduction of the Biofunctions into Traditional Metallic Biomaterials

2.1 Antibacterial Metallic Biomaterials
2.2 MRI Compatibility of Metallic Biomaterials
2.3 Radiopacity of Metallic Biomaterials
References

Chapter 3: Development of Mg-Based Degradable Metallic Biomaterials

3.1 Background
3.2 Mg-Based Alloy Design and Selection Considerations
3.3 State of the Art of the Mg-Based Alloy Material Research
3.4 State of the Art of Medical Mg-Based Alloy Device Research
3.5 Challenges and Opportunities for Mg-Based Biomedical Materials and Devices
References

Chapter 4: Development of Fe-Based Degradable Metallic Biomaterials

4.1 Background
4.2 Pure Iron
4.3 Iron Alloys
4.4 Iron-Based Composites
4.5 Surface Modification of Iron-Based Materials
4.6 New Fabrication Technologies for Iron-Based Materials
4.7 Outlook
References

Chapter 5: Development of Zn-Based Degradable Metallic Biomaterials

5.1 Backgrounds
5.2 Body Zn Distribution and Mobilization
5.3 The Physiological Function of Zn
5.4 State of the Art of the Zn-Based Alloy Material Research
5.5 Challenges and Opportunities for Zn-Based Biomedical Materials and Devices
References

Chapter 6: Development of Bulk Metallic Glasses for Biomedical Application

6.1 Background
6.2 Nonbiodegradable Bulk Metallic Glasses
6.3 Biodegradable Bulk Metallic Glasses
6.4 Perspectives on Future R&D of Bulk Metallic Glass for Biomedical Application
References

Chapter 7: Development of Bulk Nanostructured Metallic Biomaterials

7.1 Background
7.2 Representative Bulk Nanostructured Metallic Biomaterials
7.3 Future Prospect on Bulk Nanostructured Metallic Biomaterials
References

Chapter 8: Titanium Implants Based on Additive Manufacture

8.1 Introduction
8.2 AM Technologies Applicable for Ti-Based Alloys
8.3 Microstructure and Performance Evaluation of Ti-Based Alloys Fabricated by AM Technology
8.4 Prospects
References

Chapter 9: Future Research on Revolutionizing Metallic Biomaterials

9.1 Tissue Engineering Scaffolds with Revolutionizing Metallic Biomaterials
9.2 Building Up of Multifunctions for Revolutionizing Metallic Biomaterials
9.3 Intelligentization for Revolutionizing Metallic Biomaterials
References

Index

End User License Agreement

List of Illustrations

Chapter 1: Introduction

Figure 1.1 Comparison between the traditional and revolutionalizing metallic biomaterials.
Figure 1.2 Rational design and fabrication of bone tissue-like nanopatterned matrix with various groove sizes. (a) Graphical illustrations and SEM images of ex vivo bone tissue. The insert is a high-magnification image of the region indicated by the white arrow, showing the well-aligned nanostructures in bone tissue. (b) A photograph and (c) SEM images of PUA matrix nanotopography on glass slide. The spacing ratio is the ratio of the width to the spacing of nanogrooves. (d) Schematic illustration showing the engineered platforms consisting of hMSCs, HUVECs, and nanopatterned matrix.
Figure 1.3 Schematic representation of the two Zn incorporation strategies: bulk incorporation and surface incorporation.
Figure 1.4 Concept of changeable Young's modulus of implant rods during surgery.
Figure 1.5 Comparison of (a) stiffness, (b) strength, and (c) fracture toughness for metals, technical ceramics, composites, and fiber-reinforced plastic with respect to bone. CF, carbon fiber; GF, glass fiber; PA12, polyamide12; PC, polycarbonate; PE, polyethylene; PEEK, poly ether ether ketone; PLGA, poly(lactide-co-glycolide acid); PLLA, poly(l-lactic acid; PP, polypropylene; PSU, polysulfone; PTTE, polytetrafluoroethylene; and PUR, polyurethane.
Figure 1.6 The schematic diagram of the degradation behavior and the change of mechanical integrity of BM implants during the bone healing process.
Figure 1.7 Schematic illustration of (a) ECAP, (b) HPT, and (c) ARB.

Chapter 2: Introduction of the Biofunctions into Traditional Metallic Biomaterials

Figure 2.1 A schematic illustration of (a) the precipitation of ϵ-Cu on the SUS 304 steel specimen; and after galvanic corrosion, it shows (b) the depletion of ϵ-Cu and discontinuous passivated film.
Figure 2.2 Schematic diagram illustrating the antibacterial mechanism of TiNiAg alloy.
Figure 2.3 The correlation of bacterial colony-forming units per milliliter and Mg ion concentration at day 3 for all Mg-based samples (Mg–4Y, AZ31, and Mg).
Figure 2.4 Schematic presentations (not to scale) for the possible antimicrobial mechanisms of Cu ions released from a Zr-based BMG substrate.
Figure 2.5 Magnetic susceptibility variations of pure Zr and Zr–1X alloys. Asterisk (*) indicates p < 0.05 when compared with pure Zr, while # indicates p < 0.01 when compared with pure Zr.
Figure 2.6 Comparison of magnetic susceptibility for several metallic alloys.

Chapter 3: Development of Mg-Based Degradable Metallic Biomaterials

Figure 3.1 Schematic summary of the localized corrosion processes of pure Mg and WE43 at static exposure to SBF.
Figure 3.2 Optical micrograph showing a cross section through a corrosion ZE41 alloy after 18 h immersion in 0.001 M NaCl.
Figure 3.3 Experimentally determined corrosion rates for Mg alloys tested at 37 °C in MEM. All compositions are given in weight percentage.
Figure 3.4 Effect of Zr on (a) average grain size, (b) tensile properties, and (c) immersion corrosion rate of GWK alloys.
Figure 3.5 Optical micrographs of the (a) Mg–4.5Zn, (b) Mg–4.5Zn–0.5Gd, (c) Mg–4.5Zn–1.0G, and (d) Mg–4.5Zn–1.5Gd alloys etched with picric acid–ethanol–water solution.
Figure 3.6 Extruded Mg–5Zn–0.92Y–0.16Zr alloy demonstrating strong texture.
Figure 3.7 Variations of mechanical properties of Mg–2%Zn–1%Y–0.6%Zr alloy with different solution times.
Figure 3.8 Optical micrograph of GW103K: (a) as-cast (F), (b) solution-treated (T4), (c) aged 193 h (T6-193 h), and (d) corrosion rates measured by immersion in 5% NaCl solution for 3 days.
Figure 3.9 Design overview of second-generation DREAMS.
Figure 3.10 (a) Photograph of Mg-based ACL interference screws, (b) the Mg-based rings, and (c) a schematic diagram of Mg-based ring repair of the ACL.
Figure 3.11 The two cannulated screws with the same design. (a) The Ti screw (fracture compression screw, Königsee Implantate GmbH, Am Sand 4, 07426 Allendorf, Germany) and (b) MAGNEZIX^® compression screw (Syntellix AG Schiffgraben 11, 30159 Hannover, Germany).

Chapter 4: Development of Fe-Based Degradable Metallic Biomaterials

Figure 4.1 The distribution of iron in the human body.
Figure 4.2 Corrosion mechanism of microcrystalline pure iron in (a) oxygen-free and (b) oxygen-containing physiological saline.
Figure 4.3 Schematic diagram of dynamic corrosion bending pipe system.
Figure 4.4 The four biomaterial–tissue interface investigations. (a) The chemotaxis of cells to the metallic ions. (b) The cytotoxicity of metallic ions, (c) and (d) The direct test on the adhesion and proliferation of cells on the metal wires.
Figure 4.5 The laser confocal images of human aortic smooth muscle cells in the chemotaxis measure device after 4 h of culture. PCTE is at the size with Z = 0. Gradient concentration of Fe²⁺ is contained between Z = 0 and Z = 12. Between Z = 0 and Z = −8 is the cell suspension.
Figure 4.6 Image of rabbit aorta after 12 months' implantation of iron stent.
Figure 4.7 Image of pig's descending aorta after stent implantation (* marks the pure iron stent).
Figure 4.8 Micrograph of pure iron stents and Co–Cr alloy stents after 28 days' implantation in pig.
Figure 4.9 Iron wires were implanted into the artery wall (a) and the artery lumen (b); after 22 days' implantation, obvious rust can be observed surrounding the iron wire in the artery wall (c), and only part of the iron wire in the artery lumen is visible (d). (Pierson et al. 2012 [29]. Reproduced with permission of John Wiley & Sons.)
Figure 4.10 Topography of iron foil before implantation and after 1-month implantation.
Figure 4.11 SEM image of endothelial cells on the nitriding iron stent.
Figure 4.12 The average volume of implants (a) and the average surface area (b) measured by μCT scanning; there was no obvious loss of volume and surface area during implantation; (c) the weight loss of implants; there was no significant difference on the weight loss of these three kinds of experimental materials.
Figure 4.13 The distribution of iron ions at the implantation sites (blue area): (a) distribution of Fe²⁺ and Fe³⁺ ions, (b) Fe²⁺ ions, and (c) Fe³⁺ ions.
Figure 4.14 Stress–strain curves of Fe–Mn alloys.
Figure 4.15 Magnetization curves of Fe–35Mn and 316L SS specimens.
Figure 4.16 Average electrochemical corrosion rates of Fe–33Mn alloys after processing and annealing, with pure iron, pure zinc, and as-cast Fe–33Mn alloy as controls.
Figure 4.17 Immersion test results of Fe–Mn alloys.
Figure 4.18 Metallographic images of (a) as-cast and (b) as-rolled Fe–X alloys and pure iron. (c) X-ray diffraction patterns of Fe–X binary alloys. Tensile mechanical properties of (d) as-cast and (e) as-rolled Fe–X alloys at room temperature. (f) Microhardness of as-cast and as-rolled Fe–X alloys, with pure iron as control.
Figure 4.19 The microstructure images of Fe–2 wt% X (X = Pd, Ag, and C) alloys.
Figure 4.20 Metallographic images of Fe–C, Fe–P, and Fe–B alloys fabricated through powder metallurgy.
Figure 4.21 Shape recovery curve of Fe–30Mn–6Si by tensile test.
Figure 4.22 Corrosion mechanism of Fe–X composites in Hank's solution.
Figure 4.23 The viabilities of (a) L-929, (b) VSMC, and (c) ECV304 cells after culture in Fe–X composite extractions, with pure iron as control. (d) Ion concentration in material extractions.
Figure 4.24 SEM images of platelets adhered on the surface of Fe–X composites and pure iron.
Figure 4.25 Potentiodynamic polarization curves of La ion-implanted pure iron.
Figure 4.26 The morphology of HA-VSMCs (a,b) and HUVECs (c,d) after culture on the nitriding iron foils for 72 h; (a) and (c) are non-corroded area and (b) and (d) are corroded area.
Figure 4.27 2D micro-CT images of IBS scaffold after (a) 3 days', (b) 3 months', (c) 6 months', and (d) 13 months' implantation in the abdominal aorta of a rabbit.
Figure 4.28 Histopathological observation of local tissue response to IBS scaffold after (a) 3 months', (b) 6 months', and (c) 13 months' implantation in the abdominal aorta of a rabbit.
Figure 4.29 Surface morphologies of pure iron and Ag ion-implanted pure iron after 15 days immersion in Hank's solution.
Figure 4.30 Microstructure of platinum disc arrays coated with pure iron [68].
Figure 4.31 Surface morphology of platinum disc arrays coated with pure iron after immersed in Hank's solution for a week [68].
Figure 4.32 Morphologies of platelets adhered on the surface of uncoated pure iron and Pt disc-patterned pure iron [68].
Figure 4.33 The corrosion mechanism of PIPI and PCPI [69].
Figure 4.34 The microstructure of electroformed Fe, electroformed Fe annealed at 550 °C, and cast and thermomechanical treatment Fe (CTT Fe) annealed at 550 °C.
Figure 4.35 The concentration of iron ions released from electroformed Fe, annealed electroformed Fe, and annealed CTT Fe.
Figure 4.36 (a) Schematic diagram of the cold gas dynamic spraying technology, (b) electron backscatter diffraction (EBSD) image of the microstructure of 316L SS fabricated by CGDS, (c) ultimate force in microshear punch tests, and (d) the corrosion rate of experimental materials in static immersion test.
Figure 4.37 (a) The image of processed 80Fe–20SS stent and (b) corrosion rate of 80Fe–20SS stent in both static and dynamic corrosion tests, with pure iron as control.
Figure 4.38 Topography of 3D printed Fe–Mn alloy bone.
Figure 4.39 Tafel curves of 3D printed Fe–Mn alloy, with pure iron as control.
Figure 4.40 Research process of iron-based materials for biodegradable applications.

Chapter 5: Development of Zn-Based Degradable Metallic Biomaterials

Figure 5.1 Comparison of the effects of zinc intoxication versus deficiency.
Figure 5.2 Representative backscattered electron images from zinc explant cross sections after 1.5, 3, 4.5, and 6 months' time in vivo.
Figure 5.3 The optical metallographic microstructures of the as-cast (a) Zn, (b) Zn–0.15Mg, (c) Zn–0.5Mg, (d) Zn–1Mg, (e) Zn–3Mg, (f) Zn–0.5Al, and (g) Zn–1Al alloys.
Figure 5.4 SEM microstructure images of (a) as-cast and (b) homogenized Zn–3Mg samples.
Figure 5.5 Grain structure of as-cast (a,b) and extruded (c,d) Zn–1Mg. Arrow in (b) shows eutectic mixtures and arrow in (d) shows intermetallic precipitates.
Figure 5.6 Corrosion rates in SBF at three pH values obtained from the immersion tests: (a) pH 5, (b) pH 7, and (c) pH 10.
Figure 5.7 (a–d) Surface morphology of as-rolled pure Zn and Zn–1X (Mg, Ca, Sr) binary alloys after immersion in Hanks' solution for 8 weeks and (e,f) XPS analysis of the surface deposition.
Figure 5.8 Tensile tests of as-rolled pure Zn and Zn–1X (Mg, Ca, Sr) binary alloy after immersion in Hank's solution for 2 weeks (a) and 8 weeks (b).
Figure 5.9 Hemolysis rate of pure Zn and Zn-based alloys: (a) as-cast and (b) as-rolled.
Figure 5.10 (a) Morphologies and (b) number of adhered platelets on pure Zn and Zn–1X alloys.
Figure 5.11 (a) ECV304, (b) VSMC, and (c) MG63 cell viability cultured in cell culture medium, pure Zn, and Zn–1X alloy extracts (*p < 0.05, **p < 0.01 compared with pure Zn group).
Figure 5.12 Representative histology of the cross sections of mouse distal femoral shaft from Zn–1Mg, Zn–1Ca, and Zn–1Sr implanted pins group and the sham control group observed under fluorescent microscopy at week 8.
Figure 5.13 The optical metallographic microstructures of the materials: (a) as-cast pure Zn, (b) as-cast Zn–Mg–Ca, (c) as-rolled Zn–Mg–Ca, (d) as-cast Zn–Ca–Sr, and (e) as-rolled Zn–Ca–Sr.
Figure 5.14 Tensile properties of as-cast (a), as-rolled (b), and as-extruded (c) pure Zn and Zn–1Mg–1Ca, Zn–1Mg–1Sr, Zn–1Ca–1Sr ternary alloy samples.
Figure 5.15 SEM morphology of the tensile fracture surface of as-rolled pure Zn and Zn-based ternary alloy samples: (a) pure Zn; (b) Zn–1Mg–1Ca; (c) Zn–1Mg–1Sr; and (d) Zn–1Ca–1Sr.
Figure 5.16 Corrosion rate generated by electrochemical tests and weight loss tests of as-rolled pure Zn and Zn-based ternary alloy samples in Hank's solution (*p < 0.05 compared with pure Zn group).
Figure 5.17 SEM micrographs of the surface morphologies of (a) Zn–1.5Mg, (b) Zn–1.5Mg–0.1Ca, and (c) Zn–1.5Mg–0.1Sr alloys after immersion in Hank's solution for 30 days; (d–f) EDS result corresponding to the area in (a–c), respectively; and SEM micrographs of specimens with the removal of surface corrosion products: (g) Zn–1.5Mg, (h) Zn–1.5Mg–0.1Ca, and (i) Zn–1.5Mg–0.1Sr alloys.
Figure 5.18 Hemolysis rate of as-cast (a) and as-rolled (b) pure Zn and Zn-based ternary alloy samples.
Figure 5.19 MG63 cell viability cultured in cell culture medium, pure Zn, and Zn-based ternary alloy extracts (*p < 0.05, **p < 0.01 compared with pure Zn group) for 1, 3, and 5 days.

Chapter 6: Development of Bulk Metallic Glasses for Biomedical Application

Figure 6.1 The DSC trace of a Zr-based metallic glass at heating rate of 40 K min⁻¹. The onset glass transition temperature (T_g) and the onset crystallization temperature (T_x) are marked by arrows. Between T_g and T_x is the supercooled liquid region.
Figure 6.2 Compositional diagram for bone bonding. Note that the boundaries are kinetic boundaries, not phase equilibrium boundaries. Region S is a region of class A bioactivity where bioactive glasses bond to both bone and soft tissues and are gene activating.
Figure 6.3 The representative high-resolution transmission electron microscopy images of the atomic packing structure of (a) metallic glass and (b) crystal.
Figure 6.4 The yield strength (upon tension or compression) versus Young's elastic modulus for various potential biomaterials and human bones. The dash-dotted lines denote the elastic strain limits of 0.001, 0.01, and 0.1. This Figure is constructed based on the data of Table 6.2.
Figure 6.5 The Ashby plot of toughness and yield strength of various materials. Compared with polymers, crystalline metals and alloys, oxide glasses, and ceramics, metallic glasses have a good combination of high yield strength and high toughness.
Figure 6.6 The comparison of wear resistance of SK4 steel (hardened and annealed) and Zr₅₅Al₁₀Ni₅Cu₃₀ (at.%) BMG. Panels (a,c) show the gear made of SK4 steel before and after 22 h test and (b,d) show the gear made of Zr-based BMG before and after 50 h test.
Figure 6.7 The polarized corrosion curves of amorphous, polycrystalline (crystallized) and single crystalline Zr₂Ni alloys in 0.1 M NaCl aqueous solution.
Figure 6.8 The amorphous alloy shows better pitting corrosion resistance compared with its crystallized and single crystal counterparts. SEM images of (a,b) the amorphous, (c) the crystallized, and (d) the single crystal Zr₂Ni alloys in different conditions: (a) the as-polished surface and (b–d) after potentiostatic polarization at a constant potential of 100 mV SCE for 300 s in 0.1 M NaCl aqueous solution.
Figure 6.9 The three-dimensional atomic force microscopy images of the nanograined Ti-based glass composite (NGC-1, a) with a surface roughness of about 156 nm, the back surface of the melt-spun ribbon (MGR, b) with a surface roughness of about 96 nm, the upper surface of the melt-spun ribbon (MGS, c) with a surface roughness of about 3 nm, and commercial Ti alloy (Ti, d) with a surface roughness of about 238 nm. The cell number (e) and ALP content (f) was measured after cell was cultured for 1, 3, and 7 days.
Figure 6.10 Schematic diagrams of the oxide film structure of (a) Zr₅₇Nb₅Cu_15.4Ni_12.6Al₁₀ (LM106) and (b) Zr₄₁Ti₁₄Cu₁₂Ni₁₀Be₂₃ (LM1) and Zr₄₄Ti₁₁Cu₁₀Ni₁₀Be₂₅ LM1b BMGs.
Figure 6.11 A classic example of the greatly enhanced corrosion resistance in hydrochloric acid at room temperature of a Fe-based metallic glass (Fe–10Cr–13P–7C) compared with a crystalline stainless steel (type 304, Fe–18Cr–8Ni).
Figure 6.12 Metal ion releasing concentration into (a) Hank's solution and (b) artificial saliva for three Ni-free Fe-based BMGs and 316L SS.
Figure 6.13 Morphologies of L-929 cells cultured with Fe-based BMGs and 316L SS extraction media after 1, 2, and 4 days (phase-contrast microscopy).
Figure 6.14 (a) The compression strength of cortical bone and various Mg-based alloys versus elastic modulus. (b) The Zn-containing Mg-based BMGs show better corrosion resistance compared with commercial Mg alloys.
Figure 6.15 The animal studies of (a) Mg₆₀Zn₃₅Ca₅ BMG, (b) commercial WZ21 alloy in porcine muscle after 27 days, (c) Mg₆₀Zn₃₅Ca₅ BMG, and (d) commercial WZ21 alloy in subcutis after 91 days. All samples show a typical fibrous capsule foreign-body reaction (indicated by white arrows), but only the crystalline WZ21 sample shows pronounced hydrogen evolution (area between discs and fibrous capsules indicated by black arrows).
Figure 6.16 (a) The tensile stress–strain curves for Mg₆₆Zn₃₀Ca₂Yb₂ (Yb2) and Mg₆₆Zn₃₀Yb₄ (Yb4) metallic glasses show clear yield behavior and tensile plasticity. (b) The optical image of a bent Yb2 ribbon with bending angle up to 180°. (c,d) The SEM images of fracture ends of Yb2 metallic glass with different magnifications. The plastic deformation behavior transforms from shear band dominated heterogeneous to homogeneous.
Figure 6.17 (a) Schematic illustration of requirement for glass-forming ability when fabricating manufactures. When casting a bulk metallic glass sample, large glass-forming ability is required to guarantee fully amorphous atomic packing structure if the sample size is large and if the shape of the sample is complex. (b,c) The images of BMG manufactures.
Figure 6.18 The manufactures of metallic glasses, including gears, microfiber strain gauge, spiral-shaped spring, pipes, square donuts, wavy structures, springs, flexible living hinges, tweezers, sharp micro-scalpels, 3D printed scaffold, stent, membrane, and motors.

Chapter 7: Development of Bulk Nanostructured Metallic Biomaterials

Figure 7.1 Effect of grain size on the calculated volume fractions of intercrystalline regions, grain boundaries, and triple junctions, assuming a grain boundary thickness of 1 nm.
Figure 7.2 Strength and ductility of nanostructured metals compared with coarse-grained metals. Conventional cold rolling of Cu and Al increases their yield strength but decreases their ductility. The two lines represent this tendency for Cu and Al, and the % markings indicate a percentage on rolling. In contrast, the extraordinary high strength and ductility of nanostructured Cu and Ti produced by SPD clearly set them apart from coarse-grained metals.
Figure 7.3 Medical implants made of nanostructured Ti. (a,b) Plate implants for osteosynthesis. (c) Conic screw for spine fixation. (d) Device for correction and fixation of the spinal column.
Figure 7.4 3.5 mm diameter Timplant^® (a) and 2.4 mm diameter Nanoimplant^® (b).

Chapter 8: Titanium Implants Based on Additive Manufacture

Figure 8.1 Powder size distribution and morphology of the Ti–6Al–4V powder particles utilized for AM technologies: (a,c) SLM and (b,d) EBM.
Figure 8.2 Several commonly used porous units: (a) cubic; (b) hexagonal prism; (c) diamond; (d) rhombic dodecahedron; and (e) truncated octahedron.
Figure 8.3 Acetabular cup in Trabecular Titanium™ (Delta TT) for use in primary acetabular surgery.
Figure 8.4 (a) EBM system schematic: ① Electron gun assembly, ② EB focusing lens, ③ EB deflection coils (x-y), ④ Powder cassettes, ⑤ Powder cassettes, ⑥ Cylinderical build test specimen, ⑦ Build table; (b) SLM system schematic: ① Laser, ② Double rotating mirror system, ③ Beam focus lens, ④ Powder feeder system, ⑤ Building platform, ⑥ Recoater, ⑦ Powder recovery.
Figure 8.5 Schematic process of the AM technology.
Figure 8.6 (a) High-magnification SEM micrograph of the strut and (b) schematic illustration of the SLM manufacturing process of the circular strut.
Figure 8.7 Comparison of optical microstructures of EBM (a) and SLM (b) samples produced using optimum process parameters.
Figure 8.8 Optical micrograph of bulk Ti–6Al–4V fabricated by EBM. (a) Transverse cross section (perpendicular to building direction). (b) Longitudinal cross section (parallel to building direction).
Figure 8.9 Nominal compressive stress–strain curves of the meshes with different density.
Figure 8.10 SEM images of fatigue fracture surfaces showing internal porosity. (a) Multiple fatigue surfaces with internal porosity (black arrows) and (b) higher magnification of one internal pore.
Figure 8.11 SEM images of fatigue fracture surfaces showing possible initiation sites and striations. (a) Surface of the strut with sintered powder exists as well as texture lines (black arrows) and (b) higher-magnification image of portion of fracture surface in (a) showing striation-like markings (white arrow).
Figure 8.12 Histological sections of smooth surface (a,c) and rough surface (b,d) screws at 6 weeks (a,b) and 12 weeks (c,d). Fibrous tissue formation can be seen around the screw, as indicated by the red arrow, and black arrows indicate the bone tissue.
Figure 8.13 Histological analysis of bone tissue growth into porous implants (6 weeks for group A and 12 weeks for group B). White arrows, red arrows, and black arrows indicate the metal, the immature bone tissue, and the mature bone tissue, respectively.

Chapter 9: Future Research on Revolutionizing Metallic Biomaterials

Figure 9.1 (a) Optical micrograph of compact lamellar bone. (Wu et al. 2014 [1]. Reproduced with permission of Elsevier.) (b) SEM image of platelike cancellous bone; the scale bar is 1 mm. (Suchanek and Yoshimura 1998 [2]. Reproduced with permission of Cambridge University Press.) (c) SEM image of the porous structure of porous Ta–Nb alloys. (Wang et al. 2014 [3]. Reproduced with permission of Elsevier.)
Figure 9.2 Effects of different nanostructure on expression (immunofluorescence) of osteopontin (OPN) and osteocalcin (OCN) of human mesenchymal stem cells (MSCs). SQ, DS 20, and DS 50 represent square array, displaced square 20 nm, and displaced square 50 nm, respectively. The arrows indicate bone nodule formation. (Dalby et al. 2007 [6]. Reproduced with permission of Nature Publishing Group.)
Figure 9.3 Optical images of Mg/PLGA composite scaffolds with different Mg contents and pure PLGA scaffold. (Brown et al. 2015 [10]. Reproduced with permission of Elsevier.)
Figure 9.4 Pictures and SEM images of PLGA/TCP/Mg and PLGA/TCP scaffolds. (a1) PT10M scaffold; (a2) PT scaffold; (b1) SEM image of PT10M scaffold, wherein the arrow indicates the Mg particle; and (b2) SEM image of PT scaffold, wherein the arrow indicates the TCP particle. (Ma et al. 2015 [11]. http://www.nature.com/articles/srep13775. Used under creative commons license: https://creativecommons.org/licenses/by/4.0/.)
Figure 9.5 Microscopy of E. coli colonization on implant materials. (a) 317L cultured for 24 h; (b) 317L-Cu cultured for 24 h; (c) Ti-6Al-4V cultured for 24 h; (d) 317L cultured for 48 h; (e) 317L-Cu cultured for 48 h; (f) Ti-6Al–4V cultured for 48 h. (Chai et al. 2011 [18]. Reproduced with permission of Springer.)
Figure 9.6 Optical images of (a) RLC resonators made of Fe and (b) RLC resonators made of PCL-PPy. (Boutry et al. 2013 [27]. Reproduced with permission of Elsevier.)
Figure 9.7 Schematic illustration of the bioresorbable electronic stent (BES). The BES includes bioresorbable temperature/flow sensors, memory modules, and bioresorbable/bio-inert therapeutic nanoparticles. The therapeutic functions are either passive (ROS scavenging) or actively actuated (hyperthermia-based drug release) by NIR exposure.Reprinted (adapted) with permission from (Son, D., Lee, J., Lee, D.J., Ghaffari, R., Yun, S., Kim, S.J., et al. (2015) Bioresorbable electronic stent integrated with therapeutic nanoparticles for endovascular diseases. Acs Nano., 9 (6), 5937–5946). Copyright (2015) American Chemical Society.
Figure 9.8 Schematic diagram of the evolution of metallic biomaterials with time.

List of Tables

Chapter 1: Introduction

Table 1.1 Mechanical properties of traditional metallic biomaterials.
Table 1.2 Susceptibilities of selected weakly magnetic metals and alloys [77].
Table 1.3 Comparison of mechanical properties between some revolutionizing and traditional metallic biomaterials.
Table 1.4 Comparison of in vitro corrosion properties between some revolutionizing and traditional metallic biomaterials.
Table 1.5 Biological impact: red indicates a serious concern; yellow indicates a moderate concern; and green indicates minimal/no concern.

Chapter 2: Introduction of the Biofunctions into Traditional Metallic Biomaterials

Table 2.1 The mechanical properties, corrosion resistance, and antibacterial property of various antibacterial alloys.
Table 2.2 Comparison of mass magnetic susceptibilities of representative Zr–1X alloys, Zr–Mo alloys, Zr–Nb alloys, and traditional orthopedic implant materials.

Chapter 3: Development of Mg-Based Degradable Metallic Biomaterials

Table 3.1 Atomic property and solid solubility in binary Mg alloys.
Table 3.2 Slope of the liquidus line (m), equilibrium distribution coefficient (k), and growth restriction parameter m(k − 1) for alloying elements in Mg [79].
Table 3.3 Wigner–Seitz radii of selected elements (nm) [84].
Table 3.4 Mechanical strength of Mg-based alloys with LPSO.
Table 3.5 Degradation property of Mg-based alloys with LPSO.
Table 3.6 Mechanical and corrosion properties of some Mg–RE-based alloys.

Chapter 4: Development of Fe-Based Degradable Metallic Biomaterials

Table 4.1 The mechanical properties and corrosion rate of Fe-based materials for biodegradable application in comparison with WE43 alloy and 316L SS [1].
Table 4.2 The advancement of in vivo experiments of pure iron.

Chapter 5: Development of Zn-Based Degradable Metallic Biomaterials

Table 5.1 Comparison of the mechanical properties of different binary Zn-based alloys.
Table 5.2 Comparison of the corrosion rates of different biodegradable metals in Hank's solution.
Table 5.3 Comparison of the mechanical properties of different ternary Zn-based alloys.
Table 5.4 Comparison of the corrosion rates of different ternary Zn-based in Hank's solution.
Table 5.5 The corrosion rates of pure Zn and Zn–X ZnO (X = 0.25, 0.5, 1 wt%) composites [56].

Chapter 6: Development of Bulk Metallic Glasses for Biomedical Application

Table 6.1 The mechanical properties of human bones and various biomaterials.
Table 6.2 Processing methods for nanostructured metallic materials [31–34].

Chapter 7: Development of Bulk Nanostructured Metallic Biomaterials

Table 7.1 Typical nanostructured pure Ti biomaterials.
Table 7.2 Typical nanostructured Ti alloy biomaterials.
Table 7.3 Typical nanostructured stainless steel biomaterials.
Table 7.4 Other typical nanostructured metallic biomaterials.

Chapter 8: Titanium Implants Based on Additive Manufacture

Table 8.1 Common devices and companies of AM technology.
Table 8.2 Summary of the mechanical properties of dense Ti-based alloys produced by different methods.
Table 8.3 Mechanical properties of Ti–6Al–4V with different porous structures.
Table 8.4 Human clinical results of titanium implants based on additive manufacture.

Chapter 9: Future Research on Revolutionizing Metallic Biomaterials

Table 9.1 The list of the pathophysiology and recommended daily intake of some essential metallic elements in human body [12, 13].

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Preface

Traditional metallic biomaterials, including stainless steels, Co-based alloys, and titanium and its alloys, are mainly used for replacing failed hard tissue, for example, artificial hip and knee joints, bone plates, and dental implants. The key issues for the material design involve excellent mechanical property, corrosion resistance, and biocompatibility, and in body fluids, these biomaterials act as bioinert implants that occasionally exhibit surface bioactivity after a certain surface pretreatment. Since 2000, new revolutionizing metallic biomaterials have been developed such as antibacterial functionalized stainless steel and biodegradable metals (Mg based and Fe based) with bioactivity. Novel structured metallic biomaterials have been fabricated to improve performance, such as amorphous bulk metallic glasses with lower elastic modulus but high elastic limit; , nanocrystalline pure metals and alloys prepared by severe plastic deformation that exhibit improved ion release behavior or enhanced bone formability; precisely controlled porous structures for three-dimensional-printed, custom-designed bone scaffold design; and bioceramics and biopolymers with improved mechanical properties and biocompatibility. All these newly emerging revolutionized metallic biomaterials have future clinical applications, and their development shifts the original principle for alloying element selection during alloy design from passive inhibition of the released toxic metal ions (Ni in biomedical TiNi alloy) during the implantation period to the active introduction of certain metal elements with specific biofunctions into the material (e.g., adding osteoinduced Zn, Ca, and Sr into Mg to enhance bone formability) and brings new vitality in the fields of dentistry, orthopedics, cardiology, interventional therapy, gynecology, and hepatobiliary surgery. Diverse surface treatment technologies have further improved the performance of these new metallic biomaterials within the human body, making them more suitable for next-generation engineered tissue reconstruction scaffold. These metallic biomaterials as an emerging area in the twenty-first century and their bioactivities and biofunctions, including biodegradation, antibacterial and osteoinductive functions, radiopacity, and MRI compatibility, are the emphasis of this book.

The book comprises nine chapters in total. The first chapter, “Introduction,” illustrates the differences between revolutionizing and traditional metallic biomaterials and their technical considerations on alloying design. The second chapter, “Introduction of the Biofunctions into Traditional Metallic Biomaterials,” describes methods of introducing antibacterial function, MRI compatibility, and radiopacity into traditional metallic biomaterials. Chapters 3–5 discuss the development of Mg-, Fe-, and Zn-based degradable metallic biomaterials, respectively, and explain the complete degradation of biomedical magnesium alloys in body fluid. The sixth chapter, “Development of Bulk Metallic Glasses for Biomedical Application,” provides an overview on various alloy systems characterized by amorphous structure, high strength, and good biocompatibility. The seventh chapter, “Development of Bulk Nanostructured Metallic Biomaterials,” discusses different nanostructured/ultrafine-grained metallic biomaterials, whereas the eighth chapter, “Titanium Implants Based on Additive Manufacture,” demonstrates the new advanced additive manufacturing technology of fabricating titanium alloy implants. The ninth chapter, “Concluding Remarks on Revolutionizing Metallic Biomaterials,” discusses the future development direction of revolutionizing metallic biomaterials toward multifunctions and intelligentization.

The contributors to this book are Yufeng Zheng (Chapters 1, 2, 4, 5, and 9), Zhigang Xu (Chapter 3), Junqiang Wang (Chapter 6), Xiaoxue Xu (Chapter 7), and Hong Cai (Chapter 8). Special thanks are given to my students, namely, Yuanhao Wu, Dr Kejin Qiu, Wei Yuan, Tao Huang, and Meng Zhou, for their assistance in preparing the manuscript. Additionally, I would like to acknowledge the support by National Key Technologies Research and Development Program of China (Grant No. 2016YFC1102400 and 2016YFC1102402), National Key Technologies Research and Development Program of China (Grant No. 2016YFC1000900 and 2016YFC1000903), National Natural Science Foundation of China (Grant No. 31170909 and 51361165101), Beijing Municipal Science and Technology Project (Z141100002814008), NSFC/RGC Joint Research Scheme (Grant No. 51361165101 and 5161101031), and NSFC-RFBR Cooperation Project (Grant No. 51611130054).

Finally, we hope that this book will give its readers valuable insight into future directions of metallic biomaterials and biodevices and their innovative manufacturing technology. Given the diversity of topics covered, this book can be read as a reference by both university students and researchers from various backgrounds such as chemistry, materials science, physics, pharmacy, medical science, and biomedical engineering who are seeking an overview of state-of-the-art metals and alloys with biomedical applications.

Beijing, China

September 10, 2016

Y.F. Zheng

About the Authors

Yufeng Zheng is Professor in the Department of Materials Science and Engineering at Peking University, China. He started his research career at Harbin Institute of Technology in China after having obtained his PhD in materials science there. In 2004, he moved to Peking University and founded the Laboratory of Biomedical Materials and Devices at the College of Engineering. He was a winner of the National Science Fund for Distinguished Young Scholars in 2012. He has published more than 360 scientific publications including eight books and seven book chapters.

Xiaoxue Xu is Macquarie University Research Fellow in the Department of Chemistry and Biomolecular Sciences at Macquarie University, Australia. After she received her PhD in Materials Science and Engineering from the University of Western Australia, she worked there as Research Assistant Professor in the School of Chemical and Mechanical Engineering. She joined Macquarie University in 2014 and her research focuses on nanostructured biomaterials.

Zhigang Xu is Senior Research Scientist in Department of Mechanical Engineering at North Carolina A&T State University, USA. He is also affiliated to NSF Engineering Research Center for Revolutionizing Metallic Biomaterials, USA. He received his PhD in Mechanical Engineering from North Carolina A&T State University and then continued his research there as a faculty. He leads a Mg-alloy processing research group and Mg-based alloy design and processing project.

Jun-Qiang Wang is Professor in Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences. He received his PhD in Condensed Matter Physics from Institute of Physics, Chinese Academy of Sciences. From 2010 to 2014 he worked as Research Associate in Tohoku University, Japan and University of Wisconsin-Madison, USA. He joined the Ningbo Institute of Materials Technology & Engineering in 2014 and was awarded the support of 100 Talents Program of Chinese Academy of Science. His research focused on fabrication and applications of metallic glasses.

Hong Cai is Associate Professor in Department of Orthopedics at Peking University Third Hospital, China. He worked over 10 years as Attending in orthopedics. During that period, he also worked sometime as Clinical Fellow at Seoul University, Korea, University of Western Ontario, Canada and Rush University Medical Center, USA. His research interest is design and development of new implants and 3D printing in orthopedics.

New Directions and Technologies