Table Of ContentSPRINGER BRIEFS IN MATERIALS
Nicholas Travis Kirkland
Nick Birbilis
Magnesium
Biomaterials
Design, Testing,
and Best Practice
123
SpringerBriefs in Materials
For furthervolumes:
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Nicholas Travis Kirkland
Nick Birbilis
Magnesium Biomaterials
Design, Testing, and Best Practice
123
Nicholas Travis Kirkland Nick Birbilis
Department of Advanced Technologyand Department of Materials Engineering
Science forSustainable Development Monash University
NagasakiUniversity Clayton
Nagasaki Australia
Japan
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Foreword
Orthopaedic surgery today depends heavily on the development and use of bio-
materials.Thebestknownexamplesareimplantsusedforfixationoffracturesand
thoseusedinjointreplacement.Inthesesettingsbiomaterialscontributegreatlyto
the improvement of the health and wellbeing of humankind. Biomaterials for
orthopaedic surgery are an important and growing area in this rapidly changing
clinical discipline. New and improved materials are required to enhance device
performance, to improve function, deliver bioactive compounds and achieve the
goal of tissue regeneration.
Inorderfororthopaedicimplantstoachievetheirdesiredfunctionsinhumans,a
number of key factors must be addressed. From the mechanical standpoint an
implant material must have the properties to suit the desired function. The bio-
material will necessarily interface and interact with the host cells and tissues and
thereforemustbecompatiblewiththeenvironmentofthelivinghuman.Duetothe
rapid development of putative biomaterials, there is a pressing need for compre-
hensive research with respect to materials properties, biocompatibility, toxicity,
fitness for purpose and stability over time in the intended environment.
The area of biodegradable magnesium implants is one such emerging tech-
nology. There are many aspects of biodegradable magnesium materials and
implants which are in need of further research. One such area, prior to further
trialling and eventual clinical implementation, is the best-practice execution of in
vitro tests. This monograph addresses this issue, and may serve as a platform for
understanding the aspects which relate the material/alloy with its degradation.
Canberra, June 2013 Prof. Paul Smith
Director of the Department
of Clinical Orthopaedic Surgery
v
Preface
This book presents a snapshot of a rapidly growing area of research, where
althoughsignificantprogresshasrecentlybeenmade,manysubstantialchallenges
remain. The number of articles being published in the field of magnesium
biomaterials is continually rising, as seen by the Scopus citation information
(www.scopus.com) presented below. As more researchers join the field, a con-
solidated monograph which summarises the key issues and identifies the main
challenges is timely. This book is also a first step towards standardising tests and
making researchers more aware of the subtleties involved in testing magnesium
biomaterials. Our hope is that future studies will allow comparisons between
studies to be more meaningful. The field of magnesium biomaterials is indeed
interdisciplinary, embracing a diverse range of more mature fields, each of which
requires their own specific skill set. For example, alloy designers are often una-
ware of organic components in media, and biologists can struggle to understand
electrochemistry. This monograph aims to provide some guidance and the nec-
essaryunifiedplatformtobeabletoconductpractical, clinicallyrelevant,invitro
testing of biodegradable magnesium biomaterials. The book is intended for
investigators in the area of metallic implants, for existing researchers wishing to
transition to this evolving field, and for graduate students who conduct practical
experiments in the laboratory.
vii
viii Preface
Thisbookwouldnothavebeenpossiblewithoutthesupportofourinstitutions,
to which we are grateful. The compilation of the manuscript in Nagasaki will
always bring fondmemories.Thanks for assistance with figuresand discussion to
the following: Jake ‘‘Diablo’’ Cao, Kateryna Gusieva, Jay Waterman and Thanh
Loan Nguyen. A special thanks is extended to Kate Nairn for her assistance in
proofreading. Finally, a big thanks for the support of our friends and family.
Nicholas Travis Kirkland
Nick Birbilis
Contents
1 Introduction to Magnesium Biomaterials . . . . . . . . . . . . . . . . . . . 1
1.1 Changing the Way We Look at Biomaterials . . . . . . . . . . . . . . 1
1.1.1 Background to Biomaterials. . . . . . . . . . . . . . . . . . . . . 1
1.1.2 Traditional Implants: Strengths and Weaknesses. . . . . . . 2
1.1.3 The Move Towards BioDesigned Materials . . . . . . . . . . 2
1.2 Mg Alloys: Bridging the Weaknesses. . . . . . . . . . . . . . . . . . . . 3
1.2.1 History of Magnesium. . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2.2 Potential of Magnesium as a Biomaterial. . . . . . . . . . . . 4
1.3 Issues Facing Mg Biomaterial Development. . . . . . . . . . . . . . . 4
1.3.1 Primary Drawbacks of Mg Biomaterials . . . . . . . . . . . . 4
1.3.2 The Complex Nature of Biocorrosion . . . . . . . . . . . . . . 6
1.3.3 The Need for In Vitro Testing . . . . . . . . . . . . . . . . . . . 6
1.4 Future Development of Mg Biomaterials . . . . . . . . . . . . . . . . . 6
1.4.1 Understanding Biocorrosion Experiments
and Their Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.4.2 In Vitro Variables and Their Effect on Biocorrosion. . . . 8
1.4.3 Catalogue of Current Research. . . . . . . . . . . . . . . . . . . 9
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2 Magnesium Biocorrosion Experiments . . . . . . . . . . . . . . . . . . . . . 13
2.1 In Vivo Testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.1.1 Review of In Vivo Experiments Performed to Date. . . . . 13
2.1.2 In Vitro/In Vivo Relationship Not Yet Established . . . . . 14
2.1.3 Classification of In Vitro Tests. . . . . . . . . . . . . . . . . . . 17
2.2 Physical Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2.1 Mass Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2.2 Hydrogen Evolution Measurement . . . . . . . . . . . . . . . . 22
2.3 Electrochemical Testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.3.1 Potentiodynamic Polarisation . . . . . . . . . . . . . . . . . . . . 27
2.3.2 Electrochemical Impedance Spectroscopy . . . . . . . . . . . 30
2.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
ix
x Contents
3 Influence of Environmental Variables on In Vitro Performance. . . 39
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.2 Temperature Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
3.3 Buffering Systems and Effect of Solution pH
on Mg Biocorrosion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
3.3.1 pH Role in General Mg Corrosion . . . . . . . . . . . . . . . . 43
3.3.2 pH Role in Biocorrosion . . . . . . . . . . . . . . . . . . . . . . . 44
3.3.3 Buffers and pH Control. . . . . . . . . . . . . . . . . . . . . . . . 45
3.3.4 EIS of Pure Mg with Varying pH. . . . . . . . . . . . . . . . . 47
3.3.5 PDP of Mg at Different pH Values. . . . . . . . . . . . . . . . 48
3.3.6 Effect of Buffer in Immersion Tests . . . . . . . . . . . . . . . 51
3.3.7 Calcium/Magnesium Carbonate Formation. . . . . . . . . . . 52
3.4 Choice of Simulated Body Fluid. . . . . . . . . . . . . . . . . . . . . . . 53
3.4.1 High Chloride Content of Current SBFs . . . . . . . . . . . . 54
3.4.2 Design of a Biocorrosion Medium with Physiologically
Correct Cl- Levels (Kirkland’s Medium). . . . . . . . . . . . 55
3.4.3 Effect of Cl- Content on Mass Loss. . . . . . . . . . . . . . . 55
3.4.4 Mg Alloy Degradation as a Function of
Organic Components. . . . . . . . . . . . . . . . . . . . . . . . . . 56
3.4.5 Biocorrosion of Mg in Various In Vitro Media. . . . . . . . 58
3.4.6 EIS of MEM with Proteins: A Complicated System . . . . 59
3.4.7 Morphology and Composition of Corrosion Layers. . . . . 61
3.4.8 Importance of Amino Acids. . . . . . . . . . . . . . . . . . . . . 62
3.4.9 Influence of Cellular Attachment on
Mg Biodegradation . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3.5 Effects of Sample Preparation and Surface Roughness. . . . . . . . 64
3.5.1 Analysis of Corroded Surfaces . . . . . . . . . . . . . . . . . . . 66
3.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
4 Developments in Mg-based Alloys for Biomaterials. . . . . . . . . . . . 73
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
4.1.1 Mg and Its Alloys. . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
4.1.2 Corrosion of Mg Biomaterials . . . . . . . . . . . . . . . . . . . 75
4.2 Crystalline Alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
4.2.1 Influence of Alloying Elements on Dissolution of Mg. . . 77
4.3 Amorphous Alloys. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
4.3.1 Mg–Glass Biomaterials . . . . . . . . . . . . . . . . . . . . . . . . 82
4.3.2 Corrosion of Mg–Glass Biomaterials. . . . . . . . . . . . . . . 83
4.4 Alloy Design Considerations. . . . . . . . . . . . . . . . . . . . . . . . . . 85
4.4.1 Alloying Mg for Biomaterials—Toxicity
Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Contents xi
4.4.2 A Case Study in Mg Biomaterial Alloy Design . . . . . . . 88
4.4.3 Coating Mg and Biomimetic Coatings. . . . . . . . . . . . . . 90
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
5 Summary of Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . 95
5.1 Summary of Findings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
5.1.1 In Vitro Experimental Techniques. . . . . . . . . . . . . . . . . 95
5.1.2 Effects of In Vitro Variables on Biocorrosion of
Mg Alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
5.1.3 The Need for Standards. . . . . . . . . . . . . . . . . . . . . . . . 96
5.2 The Future of Mg Biomaterials. . . . . . . . . . . . . . . . . . . . . . . . 100
5.2.1 Development of More Realistic In Vitro Experiments
in the Search for In Vivo Correlation . . . . . . . . . . . . . . 100
5.2.2 Effect of Organic Compounds on Mg Biocorrosion. . . . . 101
5.2.3 Establishment of a Corrosion Database and
Neural Networks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
5.3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Appendix A: Preparation of Kirkland’s Biocorrosion Media. . . . . . . . 105
Appendix B: Experimental Techniques to Detect Protein and
Cellular Adhesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Appendix C: Categorized Collection of In Vitro and In Vivo
Studies on Magnesium Biomaterials. . . . . . . . . . . . . . . . 109
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
