Metallic Biomaterials E-Book

Yufeng Zheng

• Herausgeber: Wiley-VCH Verlag GmbH & Co. KGaA
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 597

Veröffentlichungsjahr: 2017

Beschreibung

With its comprehensive coverage of recent progress in metallic biomaterials, this reference focuses on emerging materials and new biofunctions for promising applications.
The text is systematically structured, with the information organized according to different material systems, and concentrates on various advanced materials, such as anti-bacterial functionalized stainless steel, biodegradable metals with bioactivity, and novel structured metallic biomaterials. Authors from well-known academic institutes and with many years of clinical experience discuss all important aspects, including design strategies, fabrication and modification techniques, and biocompatibility.

Leseprobe

Table of Contents

Cover

Title Page

Copyright

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

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Guide

Cover

Table of Contents

Preface

Begin Reading

Metallic Biomaterials

New Directions and Technologies

Yufeng Zheng, Xiaoxue Xu, Zhigang Xu, Junqiang Wang, and Hong Cai

Authors

Prof. Yufeng Zheng

Peking University

Department of Materials Science and Engineering

College of Engineering

No. 5 Yi-He-Yuan Road, Haidian District

100871 Beijing

China

Dr. Xiaoxue Xu

Macquarie University

Dept. of Chemistry and Biomol. Sciences

Balaclava Road

North Ryde, NSW

2109 Sydney

Australia

Dr. Zhigang Xu

North Carolina A&T State University

NSF ERC for Revolutionizing Metallic Biomaterials

NSF Center for Advanced Materials and Smart Structures

1601 East Market Street

27411 NC

United States

Prof. Junqiang Wang

Chinese Academy of Sciences

Ningbo Institute of Materials Technology and Engineering

1219 Zhongguan West Road

Ningbo City

Zhejiang Province 315201

China

Dr. Hong Cai

Peking University Third Hospital

Department of Orthopedics

No.49 North Garden Road

100191 Beijing

China

Cover

prosthesis in the background

©fotolia_Alexandr Mitiuc

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Cover Design Adam Design

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.

Chapter 1Introduction

1.1 Traditional Metallic Biomaterials

Traditional metallic materials have been typically used in medical applications such as orthopedic implants, dental applications, intravascular stents, and prosthetic heart valves. Compared with nonmetallic biomaterials, metallic biomaterials possess superior mechanical properties such as yield strength, ductility, fatigue strength, and fracture toughness [1], which are more suitable for load-bearing without large and/or permanent deformation. Application of metallic biomaterials goes back 100 years; in fact it is reported that a gold (Au) plate was used in the repair of cleft-palate defects as early as in 1565 [2]. Since then, a large number of metals and alloys, such as silver (Ag), platinum (Pt), palladium (Pd), tantalum (Ta), copper (Cu), nickel (Ni), zinc (Zn), aluminum (Al), magnesium (Mg), iron (Fe), carbon steels, stainless steels, cobalt–chromium (Co–Cr) alloys, titanium (Ti) and its alloys, and Nitinol (NiTi alloys), have been introduced into human body [3]. However, practice has shown that most of them are not perfect for implants in the human body due to various factors, such as insufficient mechanical properties, inferior corrosion resistance, and/or inadequate biocompatibility.

More recently, metallic biomaterials with better balance between good mechanical properties, a good corrosion resistance, and an excellent biocompatibility were developed. The common examples of these metallic biomaterials are type 316L stainless steel (316L SS), Co–Cr alloys, and Ti and its alloys [4]. These alloys have been approved for medical devices and surgical implants by the American Society for Testing and Materials (ASTM), and their mechanical properties are listed in Table 1.1. The 316L SS contains 0.03 wt% C, 17–19 wt% Cr, 13–15 wt% Ni, and 2–3 wt% Mo; the high Cr content gives it good resistance to a wide range of corrosive solutions. Due to its relatively low cost, availability, and easy processing, 316L SS has been employed successfully in the human body in contact with tissues and bones for several decades [6]. However, the wear resistance of 316L SS is poor, which makes it less suitable to be used as an artificial joint, because the excessive wear will lead to a rapid loosening. Compared with 316L SS, Co–Cr alloys exhibit a better wear resistance and an excellent corrosion resistance, even in chloride environments [7, 8]. Table 1.1 shows that their mechanical properties are also superior. The range of Co–Cr alloys used in clinical applications includes wrought and cast alloys. However, the elastic modulus of Co–Cr alloys (220–230 GPa) is similar to that of 316L SS (210 GPa), and both of them are much higher than that of cortical bone (20–30 GPa), leading to stress shielding in the adjacent bone and resulting in a final failure of implantation [3, 4]. Compared with 316L SS and Co–Cr alloys, Ti and its alloys exhibit lower modulus of 55–110 GPa, which is close to the bone. In addition, the passive film of TiO2 on the surface of Ti and Ti alloys gives them excellent corrosion resistance. Therefore, Ti and its alloys have been selected as the best among the aforementioned traditional metallic biomaterials for its excellent combination of mechanical properties, corrosion resistance, and biocompatibility [9].

Table 1.1 Mechanical properties of traditional metallic biomaterials.

Materials

Elastic modulus (GPa)

Yield strength (MPa)

Tensile strength (MPa)

Elongation (%)

ASTM Standard

Wrought 316L SS

190

190–690

490–1350

12–40

F138

Cast Co–28Cr–6Mo

210–253

450

655

8

F75

Wrought Co–20Cr–15W–10Ni (L605)

210

310–379

860–896

30–45

F90

Wrought Co–35Ni–20Cr–10Mo (MP 35N)

200–300

241–1586

793–1793

8–50

F562

Wrought Co–20Ni–20Cr–3.5Mo–3.5W–5Fe

—

276–1310

600–1586

12–50

F563

CP Ti (grade 1–4)

105

170–483

240–550

15–24

F67

Wrought Ti–6Al–4V ELI

110

760–795

825–860

8–10

F136

Wrought Ti–6Al–4V ELI

110

825–869

895–930

6–10

F1472

Cast Ti–6Al–4V

110

758

860

8

F1108

Wrought Ti–3Al–2.5V

—

517–714

621–862

10–15

F2146

Wrought Ti–6Al–7Nb

105

800

900

10

F1295

Wrought Ti–13Nb–13Zr

79–84

345–725

550–860

8–15

F1713

Wrought Ti–12Mo–6Zr–2Fe

74–85

897

931

12

F1813

Wrought Ti–15Mo

—

483–552

690–724

12–20

F2066

Wrought Ni–Ti

48

—

551

10

F2063

Elastic modulus data from Ref. [4, 5].

1.2 Revolutionizing Metallic Biomaterials and Their New Biofunctions

1.2.1 What are Revolutionizing Metallic Biomaterials?

According to Williams [10], the performance of any biomedical materials is controlled by two characteristics: biofunctionality and biocompatibility. Following this paradigm, many of the metallic materials used in the human body in the past have been extremely limited due to their insufficient biofunctionality and/or inferior biocompatibility [3]. Revolutionizing metallic biomaterials should have not only an excellent biocompatibility but also a specific biofunction in order to match the requirements in a variety of applications. Therefore, the revolutionizing metallic biomaterials researched and developed in recent years have various biofunctions. An interaction between the metallic biomaterials and the host is shown in Figure 1.1.

Figure 1.1 Comparison between the traditional and revolutionalizing metallic biomaterials.

(Reproduced with permission.)

1.2.2 Antibacterial Function

The most serious complication in implantation surgery is bacterial infection. However, the traditional metallic biomaterials usually do not possess antibacterial function. Therefore, in the past few decades, the bacterial colonization and antibacterial activity on metallic implant materials have been reported under in vitro and in vivo tests [11–20]. The antibacterial function of metallic biomaterials is based on the antibacterial effect of the alloying elements, such as Ag, Cu, Zn, Co, Ni, Fe, Al, Sn, and Mg [21]. And in the current research of antibacterial metallic biomaterials, Ag and Cu are the commonly used alloying elements.

The metals Ag and Cu have antibacterial functions against a broad spectrum of microorganisms and their effects depend on their doses [22, 23]. The medical uses of Ag include its incorporation into wound dressing and as an antibacterial coating on medical devices. There is little evidence to support the application of wound dressings containing Ag sulfadiazine or Ag nanoparticles for external infections [24–26]. The use of Ag coatings on urinary catheters and endotracheal breathing tubes has been reported [27, 28], which may reduce the incidence of catheter-related urinary tract infections and ventilator-associated pneumonia, respectively. Ag exhibits low toxicity in the human body, and minimal risk is expected due to clinical exposure by inhalation, ingestion, or dermal application [29]. The antibacterial action of Ag is dependent on the Ag ion, which is bioactive and in sufficient concentration readily kills bacteria in vitro. Ag and Ag nanoparticles are used as an antibacterial agent in a variety of industrial, healthcare, and domestic applications [30]. However, Ag is not an essential mineral in humans. There is no dietary requirement for Ag, and the chronic intake of Ag products can result in an accumulation of Ag or silver sulfide particles in the skin [31].

Unlike Ag, Cu is a trace metal and an essential component of several enzymes; the adult body contains between 1.4 and 2.1 mg of Cu per kg of body weight [32]. More importantly Cu can be metabolized and is much safer for the human body than Ag. As a matter of fact, in a proper range, the Cu can be excreted in the bile [15]. Cu and its alloys can be considered as natural antibacterial materials [33]. Numerous antibacterial efficacy studies indicated that Cu alloy contact surfaces have natural intrinsic properties to destroy a wide range of bacteria, as well as influenza A virus, adenovirus, and fungi [34]. Some 355 Cu alloys were proven to kill more than 99.9% of disease-causing bacteria within just 2 h when cleaned regularly [35].

Therefore, with comprehensive consideration of the antibacterial characteristic of Ag and Cu, the new antibacterial metallic biomaterials are always focused on the traditional metallic biomaterials containing Ag and/or Cu. There is a large number of studies on Ag- or Cu-bearing antibacterial stainless steels [12–14, 36–46], Ti–Ag or Ti–Cu alloys with antibacterial properties [15, 16, 47, 48], and other antibacterial metallic biomaterials containing Ag or Cu [18–20, 49, 50].

1.2.3 Promotion of Osteogenesis

From the osteogenesis perspective, the aforementioned traditional metallic biomaterials are considered to be bioinert materials. Osseointegration, which is the process of bone healing and the formation of new bone, is the clinical goal of implant surgery. The implant and the bone cells are considered well osseointegrated when new bone cells form, proliferate, and differentiate on the implant [4]. In order to obtain a firm binding between the metallic implants and the surrounding bone, the bioactive interface must facilitate a better bone regeneration and expedited healing. There are many studies that focus on the surface modifications to gain an excellent bone regeneration ability. Some strategies experimented to improve bone integration of metallic implants are development of porous surface, coating of nanoceramic particles, hydroxyapatite coating, oxide coating, and thermal heat treatment of surfaces.

By using rapid prototyping (RP) technique and electrodeposition method, Lopez-Heredia et al. [51] have built porous Ti scaffolds with a calcium phosphate (CaP) coating and then studied their osteogenic property. The subcutaneous implantation results showed the presence of mineralized collagen but not mature bone tissue. Even so, the study opened up the possibility of using high-strength porous scaffolds with appropriate osteoconductive and osteogenic properties to reconstruct large skeletal parts in the maxillofacial and orthopedic fields. By using another technique called laser engineered net shaping (LENS™), Balla et al. [52] have demonstrated that the modulus of porous Ta can be tailored between 1.5 and 20 GPa by varying its porosity. And the in vitro biocompatibility tests showed excellent cellular adherence, growth, and differentiation with abundant extracellular matrix formation on porous Ta structures, which indicated a promotion in biological fixation. On the modified microarc oxidation (MAO)–treated Ti implants surface, fast osteoid deposition comprising high content of Ca, P, C, and N was found in the work of Ma et al. [53]. MAO-treated Ti materials have been proved to exhibit good CaP inducement capability in vivo, which could accelerate bone tissue growth and shorten the osseointegration time. A highly controlled and reproducible electrochemical polishing process can be used to pattern and structure the surface of Ti–6Al–4V alloy at both the nano- and microscale [54]. The treated surface with a nanoscale TiO2 layer influenced the program of cellular differentiation culminating in osteogenesis. Chai et al. [55] have evaluated the in vitro and in vivo osteogenesis of a β-tricalcium-phosphate (TCP)-coated Mg alloy. The in vitro cell tests showed that the β-TCP coating provided the Mg alloy with a significantly better surface cytocompatibility, and in vivo results also confirmed that the β-TCP coating exhibited greatly improved osteoconductivity and osteogenesis in the early 12 weeks postoperative period. To mimic the extracellular microenvironment of bone, Hu et al. [56] constructed a bioactive multilayered structure of gelatin/chitosan pair, containing bone morphogenetic protein 2 (BMP2) and fibronectin (FN) on the Ti–6Al–4V surface via a layer-by-layer assembly technique. The in vivo tests demonstrated that the multilayer coated Ti–6Al–4V implants promoted the bone density and new bone formation around them after implantation for 4 and 12 weeks, respectively, and showed that the coatings are beneficial for osteogenesis and integration of implant/bone. In another study, they prepared the apatite/gelatin nanocomposite onto Ti substrates via a coprecipitation method [57]. The results showed that the deposition of apatite/gelatin nanocomposite improved bone density and bone–implant contact rate significantly, and that deposition enhanced the bone osseointegration of Ti-based implants. Bone tissue regeneration in load-bearing regions of the body requires high-strength porous scaffolds capable of supporting angiogenesis and osteogenesis. Gotman et al. [58] produced the porous Nitinol scaffolds with a regular 3D architecture resembling trabecular bone using an original reactive vapor infiltration technique. The results of co-culture system of microvascular endothelial cells demonstrated the formation of prevascular structures in trabecular Nitinol scaffolds. It suggested that the strong osteoconductive load-bearing trabecular Nitinol scaffolds could be effective in regenerating damaged or lost bone tissue. Besides the aforementioned methods, Kim et al. [59] studied the synergistic effects of nanotopography and co-culture with human umbilical endothelial cells (HUVECs) on osteogenesis of human mesenchymal stem cells (hMSCs). The rational design and fabrication of bone tissue-like nanopatterned matrix are shown in Figure 1.2. Their findings suggested that the nanotopography contributed to the osteogenesis more than co-culture with HUVECs did. However, what is more important than the results is this study provided a new insight on the importance of tissue-inspired nanotopography and co-culture systems in designing engineered platforms for stem cell-based bone tissue engineering, as well as for the fundamental study of stem cell biology. Lee et al. [60] studied the bone regeneration around N-acetyl cysteine-loaded nanotube Ti (NLN–Ti) dental implant in a rat mandible. The results of μ-computed tomography revealed an increase of newly formed bone volume and bone mineral density in the mandibles of Sprague Dawley rats. The immunohistochemical analysis showed a significantly higher expression of BMP-2, BMP-7, and heme oxygenase-1 and reduced expression of receptor activator of nuclear factor-κB ligand. All the data indicate that NLN–Ti implants enhance osseointegration and highlight the value of the small animal model in assessing diverse biological responses to dental implants.

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.

(Kim et al. 2013 [59]. Reproduced with permission of Elsevier.)

Mg alloys have been investigated in different fields of medicine and represent a promising biomaterial for implants due to characteristics like bioabsorbability and osteoinduction. Lensing et al. [61] tested a bioabsorbable Mg alloy serving as total ossicular replacement prostheses. The in vivo results revealed a considerable degradation of implants and obvious bone formation was found 3 months after implantation. Although the Mg alloy corroded before completing the bone reconstruction in time, the increased osteoinduction on the stapes base plate resulted in a tight bone–implant bonding. Therefore, the authors think that the combined application of Mg implant and coating would be a promising solution for improving the bone integration of implants.

In a recent study, Qiao et al. [62] reported the stimulation of bone growth following Zn incorporation into biomaterials. Zn is incorporated into the subsurface of TiO2 coatings (Zn-implanted coatings) by plasma immersion ion implantation and deposition (PIII&D), with the “bulk-doped” coatings prepared by plasma electrolyte oxidation control; the schematic representation of the two Zn incorporation strategies are shown in Figure 1.3. The results revealed that the Zn-implanted coatings resulted in a significant improvement of osteogenesis in vitro and in vivo compared with the “bulk-doped” coatings. Molecular and cellular osteogenic activities demonstrate that rat BMSCs cultured on the Zn-implanted coatings have higher ALP activity and upregulated osteogenic-related genes (OCN, Col-I, ALP, Runx2). In vivo osseointegration studies also showed an early-stage new bone formation and a larger bone contact ratio (12 weeks on the rat model) on the Zn-implanted coating.

Figure 1.3 Schematic representation of the two Zn incorporation strategies: bulk incorporation and surface incorporation.

(Qiao et al. 2014 [62]. Reproduced with permission of Elsevier.)

1.2.4 Reduction of In-stent Restenosis

Cardiovascular stent materials should possess not only a good cell affinity but also a mechanical property similar to that of blood vessels. Coronary stent implantation has been proven to be an effective technique for the prevention of restenosis in native coronary vessels compared with angioplasty alone. Despite advances in polymer and drug technology, the underlying stent platform remains a key determinant of the clinical outcomes [63]. Currently, the restenosis rates after bare-metal stent (BMS) implantation are still as high as 20–40% at 6 months [64]. Drug-eluting stents (DESs) were shown to be safe and feasible in reducing restenosis [65, 66], but their efficacy and safety have not been confirmed in all clinical settings, especially with regard to treating in-stent restenosis. So reducing the in-stent restenosis remains to be a big challenge. From the angle of biomaterials, the stents should promote the proliferation of vascular endothelial cells (VECs), which hereby accelerate the process of revascularization. In the meantime, they obviously inhibit the proliferation of vascular smooth muscle cells (VSMCs) [17].

Ren et al. [67] studied the effect of trace amount of Cu ions released from Cu-bearing stainless steel on reduction of in-stent restenosis. The in vitro experimental results proved that this Cu-bearing steel could not only inhibit the proliferation of VSMCs for reducing the formation of thrombosis but also promote the proliferation of VECs needed for the revascularization. However, because there were no in vivo experimental results to support it, further animal study should be done.

Over the last 10 years, considerable efforts have been made to develop fully bioresorbable devices called bioresorbable scaffolds (BRSs). BRS technology has gradually matured, and there are numerous devices available, which are currently undergoing preclinical or clinical testing. Mg is an attractive alloy for this concept [68]. The first generation of bioabsorbable metal scaffolds (AMS-1; Biotronik AG, Bülach, Switzerland) was made from a WE43 alloy without drug elution. In porcine coronary arteries, the neointimal tissue proliferation was significantly less in the stented segments with the Mg alloy scaffold as compared with a control group of stainless steel stents [69]. Compared with AMS-1 strut thickness being 165 µm, the strut thickness of DREAMS first generation (DREAMS 1G) was reduced to 120 µm. Moreover, to reduce neointimal growth, the DREAMS was coated with a 1 µm bioresorbable poly(lactide-co-glycolide acid) (PLGA) polymer matrix containing the antiproliferative drug paclitaxel (0.07 µg mm−2) [70]. Then the DREAMS second generation (DREAMS 2G) with radiopaque markers at both ends (made from Ta) was developed. As a result, DREAMS 2G has slower dismantling and resorption rate. To further reduce the neointima formation, the DREAMS 2G was coated with a bioresorbable polylactic acid polymer (7 µm) featuring sirolimus at a dose of 1.4 µg mm−2. Combining the material characteristics of Mg and the antiproliferative featuring of sirolimus, the DREAMS 2G showed a significant reduction of in-stent restenosis.

1.2.5 MRI Compatibility

Magnetic resonance imaging (MRI) is a technology developed in medical imaging that is probably the most innovative and revolutionary other than computed tomography. MRI has a wide range of applications in medical diagnosis and there are estimated to be over 25 000 scanners in use worldwide [71]. However, most of the currently used implants for cochlear implants, intravascular stents, cardiac pacemakers, and artificial joints are challenged by their unsatisfactory MRI compatibility, because the implants contain ferromagnetic elements [72]. MRI diagnosis is inhibited by the presence of metallic implants, because they become magnetized in the intense magnetic field of the MRI instrument and may produce image artifacts and therefore prevent accurate diagnosis [73, 74]. Hence, improving the MRI compatibility of novel biomedical metallic materials for implants is a very important research topic.

The two trends of development of MRI interventional tools are producing new material with no artifacts and MRI visualizing and guiding of percutaneous devices [75]. Generally, the artifacts affected by MRI decrease with the magnetic susceptibility of the implants [76]. The susceptibilities of selected weakly magnetic metals and alloys are listed in Table 1.2, with water and human tissues as control. In recent years, some studies have focused on the novel MRI-compatible Mg, Zr, and Nb alloys for implants [72, 74, 78–84]. More details can be seen in Section 2.2.

Table 1.2 Susceptibilities of selected weakly magnetic metals and alloys [77].

Materials

Density/

ρ

(10

3

kg m

−3

)

Susceptibility/

χ

(×10

−6

)

Water (37 °C)

0.933

−9.05

Human tissues

~(1.0 to 1.05)

~(−11.0 to −7.0)

Au

19.32

−34

Cu

8.92

−9.63

Mg

1.74

11.7

Zr

6.49

109

Mo

10.22

123