Acta Biomaterialia 36 (2016) 1–20

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Acta Biomaterialia
journal homepage: www.elsevier.com/locate/actabiomat

Review article

Recent advances in bulk metallic glasses for biomedical applications

H.F. Li, Y.F. Zheng ⇑
Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871, China

a r t i c l e i n f o a b s t r a c t

Article history: With a continuously increasing aging population and the improvement of living standards, large
Received 23 October 2015 demands of biomaterials are expected for a long time to come. Further development of novel biomateri-
Received in revised form 17 March 2016 als, that are much safer and of much higher quality, in terms of both biomedical and mechanical proper-
Accepted 31 March 2016
ties, are therefore of great interest for both the research scientists and clinical surgeons. Compared with
Available online 1 April 2016
the conventional crystalline metallic counterparts, bulk metallic glasses have unique amorphous struc-
tures, and thus exhibit higher strength, lower Young’s modulus, improved wear resistance, good fatigue
Keywords:
endurance, and excellent corrosion resistance. For this purpose, bulk metallic glasses (BMGs) have
Bulk metallic glasses
Liquid metal
recently attracted much attention for biomedical applications. This review discusses and summarizes
Advanced materials the recent developments and advances of bulk metallic glasses, including Ti-based, Zr-based, Fe-based,
Biomaterials Mg-based, Zn-based, Ca-based and Sr-based alloying systems for biomedical applications. Future research
Clinical applications directions will move towards overcoming the brittleness, increasing the glass forming ability (GFA) thus
obtaining corresponding bulk metallic glasses with larger sizes, removing/reducing toxic elements, and
surface modifications.

Statement of Significance

Bulk metallic glasses (BMGs), also known as amorphous alloys or liquid metals, are relative newcomers in
the field of biomaterials. They have gained increasing attention during the past decades, as they exhibit
an excellent combination of properties and processing capabilities desired for versatile biomedical
implant applications. The present work reviewed the recent developments and advances of biomedical
BMGs, including Ti-based, Zr-based, Fe-based, Mg-based, Zn-based, Ca-based and Sr-based BMG alloying
systems. Besides, the critical analysis and in-depth discussion on the current status, challenge and future
development of biomedical BMGs are included. The possible solution to the BMG size limitation, the brit-
tleness of BMGs has been proposed.
Ó 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Ti-based bulk metallic glasses for biomedical implants and devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.1. Mechanical properties of biomedical Ti-based BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.2. Corrosion behavior of biomedical Ti-based BMGs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.3. Biocompatibility of biomedical Ti-based BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3. Zr-based bulk metallic glasses for biomedical implants and devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.1. Mechanical properties of biomedical Zr-based BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.2. Corrosion behavior of biomedical Zr-based BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.3. Biocompatibility of biomedical Zr-based BMGs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
4. Fe-based bulk metallic glasses for biomedical implants and devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
4.1. Mechanical properties of biomedical Fe-based BMGs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
4.2. Corrosion behavior of biomedical Fe-based BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
4.3. Biocompatibility of biomedical Fe-based BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

⇑ Corresponding author.
E-mail address: yfzheng@pku.edu.cn (Y.F. Zheng).

http://dx.doi.org/10.1016/j.actbio.2016.03.047
1742-7061/Ó 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
2 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20

5. Biodegradable bulk metallic glasses designed for temporary implants and devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5.1. Biodegradable Mg-based BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5.2. Biodegradable Ca-based and Sr-based BMGs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
5.2.1. Biodegradable Ca-based BMGs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
5.2.2. Biodegradable Sr-based BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
5.3. Biodegradable Zn-based BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
6. Future research directions and challenges for BMGs as potential biomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
6.1. BMG composites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
6.2. BMG foams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
6.3. Removing toxic and noble alloying elements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
6.4. Improving BMG critical sizes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
6.5. Surface modification of BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
6.5.1. Surface modification of non-biodegradable BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
6.5.2. Surface modification of biodegradable BMGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
6.6. Metallic glass coatings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
7. Concluding remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

1. Introduction resonance imaging, which cause various problems in clinical appli-

With the improvement of the living standards and the develop-
ment of science and technology, biomaterials have developed
rapidly and helped in improving the quality of life and longevity
of human beings greatly. Metallic biomaterials have the longest
history among the various kinds of biomaterials. It has been
reported that people began to use metal dental implants thousand
years ago, which can be tracked back to 200 CE [1]. Stainless steel,
vitallium (Co-Cr alloys), pure Ti and Ti alloys, pure Zr and Zr alloys
are widely used as artificial hip joints, cardiovascular stents, artifi-
cial knee joints, bone plates, dental implants, etc. Besides, pure Mg
and Mg alloys, pure Zn and Zn alloys have been studied and devel-
oped as biodegradable materials aiming to be useful in the clinical
cases that need temporary supporting or fixation (such as plates
and screws for bone fracture fixation, stents for cardiovascular
repair), without second operation to be removed after finishing
their functions [2,3]. However, these conventional crystalline
metallic alloys have disadvantages such as low strength, high elas-
tic modulus, low wear resistance, prone to crevice corrosion, pit-
ting corrosion as well as stress corrosion cracking (SCC) and high
cycle fatigue failure, incompatibility with X-ray or magnetic
Fig. 1. Illustration of the relationship of the three materials, i.e. bioglasses,
biometallic alloys and biomedical BMGs.
cation [4]. For instance, poor corrosion resistance can cause rela-
tively high toxic ion release, such as Ni +, Cr3+ and Co2+ into
human and it is well known that these ions usually lead to adverse
reactions when their concentrations rise above certain thresholds.
Most of the conventional metallic biomaterials possess much
higher elastic modulus compared to that of human bone. And the
mismatching modulus can cause stress shielding of bone, resulting
in bone resorption and loosening of the implant after a period of
implantation [5]. Further development of novel biomaterials, that
are much safer and of much higher quality, in terms of both
biomedical and mechanical properties, are therefore of great inter-
est for both the research scientists and clinical surgeons.
Efforts to discover alternatives to conventional biometals led to
the discovery of bioglass in the early 1970s [6], since which time
various kinds of bioglasses have been developed. Key bioglass sys-
tems include the typical S45P7 (SiO2-CaO-Na2O-P2O5-B2O3), 45S5
(SiO2-CaO-Na2O-P2O5) and S52P3 (SiO2-CaO-Na2O-P2O5-B2O3-
Al2O3) systems, all of which have been widely used in biomedical
applications, in contexts ranging from otology to cancer
treatment [7]. Unfortunately, most of the bioglasses developed
did not represent a real alternative to biometals, since they had
unsatisfactory mechanical properties and thus remained unsuitable
for clinical applications that need place them in load-bearing
sites.
Metallic glasses (MGs), also known as amorphous alloys and liq-
uid metals, emerged as a newcomer to the clubs of metallic mate-
rials in 1960, with the formation of the first metallic glass of
Au75Si25 being reported in Nature journal by Duwez P’s research
team at Caltech, USA [8]. MGs have excellent physical and chemical
functions such as high toughness and corrosion resistance, but the
limited specimen sizes originally achievable (normally in the range
of microns) severely restricted the study and application of MGs.
These limitations were overcome by the development of bulk
metallic glasses (BMGs) with much lower critical cooling rates
(<100 K/s).
BMGs had received a lot of attention during the last two dec-
ades for their high strength and elasticity which are the conse-
quences of their amorphous structure and concomitant lack of
dislocations and associated slip planes. From the early 1990s, a ser-
ies of new kinds of BMGs with the multicomponent chemistry and
excellent glass forming ability (GFA) have been discovered in Zr-,
Mg-, La-, Pd-, Ti-, and Fe-based systems by various solidification
methods. These BMGs exhibited strong resistance to crystallization
in the super-cooled liquid state and demonstrated excellent
mechanical and physical properties.
 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20 3

Table 1
Comparison of bioglasses, biometals and biomedical bulk metallic glasses.

Systems Chemical Classification Microstructure Preparation Mechanical Current/potential clinical

composition methods properties applications
Bioglasses Na2O-CaO-SiO2- Biodegradable: 45S5, phosphate-based glasses, Amorphous Sol-gel, Low strength, low Dental repairs, fillers, middle ear
P2O5 oxides borate-based glasses melting Young’s Modulus ossicular replacements
Non-biodegradable: 60S3.8, 65S
Biometals Ti, Zr, Fe, Mg, Ca, Biodegradable: Mg and Mg alloys, Fe and Fe Crystalline Conventional High strength, high Dental implants, stents,
Zn, Sr metals alloys, W casting Young’s Modulus orthopedic surgeries, sutures
Non-biodegradable: Ti and Ti alloys, 316L SS,
304SS, Zr and Zr alloys
Biomedical Ti, Zr, Fe, Mg, Ca, Biodegradable: Mg-based BMGs, Ca – based Amorphous Modified High strength, low Dental implants, fillers, stents,
BMGs Zn, Sr metals BMGs, Zn-based BMGs, Sr-based BMGs casting Young’s Modulus orthopedic surgeries, sutures
Non-biodegradable: Ti-based BMGs, Zr-based
BMGs, Fe-based BMGs

Table 1 compares conventional bioglasses, biometals and biomed-

Fig. 2. Mechanical comparisons of conventional bioglasses, biometallic alloys and
the novel developed biomedical BMGs.
As shown in Fig. 1, BMGs combine the microstructure of the
conventional amorphous bioglasses and the elemental metal com-
positions of the conventional crystalline biometallic alloys. As a
result, BMGs represent a class of materials that may combine the
physical and chemical properties of both bioglasses and conven-
tional crystalline metallic materials.
A quick comparative review of characteristics and properties for
these three classes of materials underscores the promise of BMGs.
ical BMGs according to chemical composition, microstructure,
preparation methods and mechanical properties. Furthermore,
Fig. 2 illustrates the compression strengths and Young’s modulus
for these three classes of materials. Table 1 and Fig. 2 demonstrate
that bio-glasses have low strength and low Young’s moduli while
conventional metallic biomaterials have high strength and high
Young’s moduli. In contrast, biomedical BMGs, with combined
characteristics of bioglasses and biometals, show high strength
and low elastic moduli making them, in theory, highly suitable
for biomedical applications. In particular, the biomedical BMGs’
extremely high elastic limit of 2% compares favorably with bone’s
elastic limit of 1%, suggesting that biomedical BMGs would be
unique in their ability to flex elastically with the natural bending
of the bones and would consequently distribute stresses more uni-
formly than current materials, minimizing stress concentrations,
reducing stress shielding effects, and thus achieving faster healing
rates. Thanks to the unique properties of biomedical BMGs, the
BMG bone screws could have a thinner shank and deeper threads
thus yielding greater holding power to the fracture bones. Com-
pared to conventional 316L SS stents, biomedical BMG stents
would require only one third of the cross-section of the strut and
would have more than five times the deflection [9].
In the last decades, some of the BMGs were developed specially
for biomedical purpose, and both in vitro and in vivo testing had
been done to evaluate the feasibility as biomaterials. Several
biomedical implants and devices made out of BMGs have been
designed and developed in the past decades. As illustrated in

Fig. 3. Illustration of biomedical implants and devices made out of BMGs. (a) Commercial martensitic steel surgical blade coated with ZrCuAlAgSi BMG film (left) and
ZrCuAlAgSi BMG surgical blade (right). (b) The ezlase Diode Dental Laser System, from Biolase Technology, uses Liquidmetal in its housing. (c) BMG medical stapling anvils.
(d) Liquidmetal Alloys in Minimally Invasive Medical Devices.
4 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20

Table 2
Summary of biomedical Ti-based BMG systems and their mechanical properties.

Chemical composition Preparation method Critical Compressive Young’s Specific strength Vickers Reference
(at.%) diameter/thickness (mm) fracture modulus (kN m/kg) hardness
strength (rf) (Hv)
(MPa) (kg mm 2)
Ti40Zr10Cu36Pd14 Arc-melting/copper mold 6 1950 82 270 — [19]
casting
Ti75Zr10Si15 and Arc-melting/ejecting onto a 30 lm thick ribbons >2000 — — 790 and [21]
Ti60Nb15Zr10Si15 single copper 660
Ti40Zr10Cu38Pd12 Arc-melting/copper mold — — Around — 765 [22]
casting 100 (7.5 GPa)
Ti45Zr10Cu31Pd10Sn4 Spark plasma sintering 15 2060 — 310 (calculated — [20]
(SPS) (sintering at from the data of
643 K) strength and
density)
Ti45Zr10Cu31Pd10Sn4 Arc-melting/copper mold 4 1970 95 — 650 [23]
casting
Ti45Ni15Cu25Sn3Be7Zr5 Arc-melting/copper mold 5 2480 — — 715 [17]
casting
(Ti0.45Zr0.1Pd0.1Cu0.31Sn0.4) Arc-melting/copper mold 3–5 1670–2150 97–119 — — [24]
100 xMx (M: Ta and Nb) casting
(x = 1–5)
(Ti40Zr10Cu36Pd14)100–xNbx Arc-melting/copper mold 2 2050 80 — — [25]
(x = 1, 3, 5) casting
(Ti40Zr10Cu38Pd12)100–xNbx Arc-melting/copper mold Fully amorphous for x = 0 and 1200–2000 100–106 — 612–816 [26]
(x = 0, 2, 3, 4) casting partially amorphous for x = 2, 3 (6–8 GPa)
and 4 with 2 mm in diameter
Ti40Zr10Cu34Pd14Sn2 Arc-melting/copper mold 10 2000–2150 — — — [27]
casting
Ti40Zr10Cu32Pd14Sn4 Arc-melting/copper mold 10 2000–2150 — — — [27]
casting
Ti43.15Zr9.59Cu36.24Ni9.06Sn1.96 Arc-melting/copper mold 3 2640 — 400 — [18]
casting
Ti41.5Zr2.5Hf5Cu37.5Ni7.5Si1Sn5 Arc-melting/copper mold 6 2000 ± 78 80 ± 12 — 600 [28]
casting
Ti41.5Zr2.5Hf5Cu42.5Ni7.5Si1 Arc-melting/copper mold 5 2080 103 — — [29]
casting
Ti43.3Zr21.7Ni7.5Be27.5 (LM-010) Arc-melting/copper mold — 1790 (tensile 95 351 — [16]
casting yield
strength)
Ti41.3Cu43.7Hf13.9Si1.1 Arc-melting/copper mold 3 1685 95 — — [30]
casting
Ti40Zr25Ni12Cu3Be20 Arc-melting/copper mold — 1932 95 — 530 [31]
casting
Ti47Cu38Zr7.5Fe2.5Sn2Si1Ag2 Arc-melting/copper mold 7 2080 100.4 ± 0.1 588 ± 6 [32]
casting

Fig. 3, these biomedical devices include surgical blades with
improved sharpness (Fig. 3a) [10], the housing of the iLase
(Fig. 3b), which is a handheld pen laser for dental procedures,
attracted by the unique strength, ability to be molded to a thin wall
thickness, and ornamental finish of BMGs [11], medical stapling
anvils (Fig. 3c), considering the top 4 advantages BMGs providing:
1) Superior As-Cast Surface Finishes; 2) Pocket-to-pocket dimen-
sional accuracy; 3) Molded-in Camber for proper alignment to sta-
ple cartridge when clamped to tissue; 4) Lot-to-lot variability
limited to mold cavity-to-cavity variability [12], and Minimally
Invasive Medical Devices (Fig. 3d), with enhanced precision, dura-
bility, repeatability and more convenient manufacturing process-
ing [13]. Besides the above mentioned biomedical devices, BMGs
are promising candidates as biomedical implants. It has been
reported that BMGs could increase the strength, corrosion resis-
tance, biocompatibility and longevity of biomedical implants,
which are aimed to be used as cardiovascular stents [14] and
orthopedic implants (such as bone plates, bone screws, articulating
surfaces, artificial prostheses, absorbable sutures, dental implants
and fillers) [15]. In the design and development of biomedical
BMGs, the main chemical compositions of the conventional crys-
talline biomedical alloys, i.e. Ti alloys, Zr alloys, stainless steels,
Mg alloys, Zn alloys were taken as references. Based on this consid-
eration, there are the corresponding BMGs with the same main
chemical compositions explored as potential biomaterials, includ-
ing Ti- based BMGs, Zr-based BMGs, Fe-based BMGs, which are also
known as amorphous stainless steels, Mg-based BMGs and Zn-
based BMGs. In addition, Ca-based BMGs and Sr-based BMGs are
developed as potential biodegradable materials as well, consider-
ing the nutritional functions of the main alloying elements of Ca
and Sr.
In the following paragraphs, the recent developments and
advances of these BMGs respectively as novel biomedical materials
will be summarized and comprehensively reviewed.
 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20
Fig. 4. (A) Compressive stress–strain curve of the Ti40Zr10Cu36Pd14 glassy alloy rod
with a diameter of 2.5 mm. (B) Compressive stress–strain curves of three Ni-free Zr-
based BMGs. (C) Uniaxial compressive true stress–strain curves for four Fe–Cr–Mo–
P–C–B BMGs: (a) Fe63Cr3Mo12P10C7B5, (b) Fe64Cr3Mo10P10C10B3, (c) Fe63Cr3-
Mo10P12C10B2 and (d) Fe71Mo5P12C10B2.
2. Ti-based bulk metallic glasses for biomedical implants and
devices
As summarized in Table 2, series of Ti-based BMGs have been
investigated for biomedical application, ranging from Ni and Be
containing Ti-Zr-Ni-Be [16], Ti-Ni-Cu-Sn-Be-Zr [17], Ti-Zr-Cu-Ni-
Sn [18] systems to the Ni and Be free Ti-Zr-Cu-Pd [19], Ti-Zr-Cu-
Pd-Sn [20] and Ti-Zr-Si [21] systems.
2.1. Mechanical properties of biomedical Ti-based BMGs
Mechanical properties of materials have great importance due to
their role for applications. As shown in Table 2, Ti-based BMGs have
relatively low Young’s modulus (80–120 GPa), high fracture
strength (1700–2500 MPa), and excellent specific strength. Fig. 4
(A) shows the typical compressive stress–strain curve of the
5
Ti-based BMG and it demonstrates that the alloy exhibits an elastic
elongation of about 2.3%, followed by a small serrated plastic
elongation of about 0.5%, indicating that the cast alloy possesses
certain ductility. The fracture took place along the maximum shear
stress plane, which was declined by about 45° to the direction of
applied compressive load. The SEM image of the fracture surface
showed that the dominant fractographic feature is a smooth and
well-developed vein pattern, which is caused by viscous flow of
materials in shear band [19].
2.2. Corrosion behavior of biomedical Ti-based BMGs
The study of the corrosion behavior of BMGs is of great impor-
tance to understand their chemical and environmental stability.
Corrosion processes in humid environment are mostly based on
electrochemical reactions. First of all, the corrosion rate of multi-
component glass-forming alloys is determined by the electrochem-
ical reactivity of the main alloying elements. Nevertheless, in more
detail, aspects of thermodynamic metastability, unusual atomic
structure and chemical homogeneity due to the ideally single-
phase nature are decisive as well.
Researchers have studied the corrosion behavior of Ti-based
BMGs in different kinds of simulated body fluids, including phos-
phate buffered solution (PBS) [16], Ringer’s solution [21], Hank’s
balanced salt solution (HBSS) [22,26], 1 mass% Lactic acid [23,24]
and specific simulated body fluid (SBF) [33]. Studies have
shown that Ti-based BMGS exhibited passive behavior at the
open-circuit potential with a low corrosion rate; a susceptibility
to localized corrosion in the form of pitting corrosion; the localized
corrosion resistance was statistically equivalent to, or better than,
the conventional crystalline biomedical alloys, including 316L
stainless steel [16], pure Ti and Ti-based biomedical alloys (such as
Ti-6Al-4V) [23,24]. After 15 days immersed in SBF, hydroxyapatite
(HA), one of the main chemical compositions of human natural
bones and teeth, was reported to have deposited on the Ti-based
BMG alloy surfaces [33], which would guarantee the biocompati-
bility of Ti-based BMGs.
2.3. Biocompatibility of biomedical Ti-based BMGs
Biocompatibility of the selected materials has a great impor-
tance as well. It is described as the ability of the material to exist
in contact with tissues of the human body without causing a
non-acceptable degree of harm. That depends on numerous factors.
Firstly, it concerns the human body response to it or the cell-
biological activity of the implant. The higher the bioactivity, the
higher is the biocompatible with surrounding tissues. And the sec-
ond main factor is the material degradation in the body environ-
ment as a consequence of low wear and corrosion resistance.
This could result in a release of the constituent metal ions or par-
ticles of the implant alloy system into the body causing several
reactions including allergic and toxic ones. Hence, choosing mate-
rials with high wear and corrosion resistance as well as including
non-toxic and non-allergenic elements is of high significance.
Researchers have studied the biocompatibility of Ti-based
BMGs via both in vitro cell response (via MTT/CCK8 assay and cell
morphology observations) and in vivo animal implants. And results
have demonstrated that Ti-based BMGs showed better biocompat-
ibility than the conventional crystalline Ti-6Al-4V and Ti-45Ni
alloys for both the in vitro human osteoblast SaOS2 cells [34], mur-
ine fibroblast cells (L929 cell and NIH3T3 cell) culture and in vivo
beagle dogs implantation [28]. Fig. 5 shows the SEM images of
L929 and NIH3T3 cells on crystalline pure Ti and Ti41.5Zr2.5Hf5C
u37.5Ni7.5Si1Sn5 (TZHCNSS) BMG surfaces after 4 days of incuba-
tion [28]. It can be observed from Fig. 5 that cells could attach very
6 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20

well on all sample surfaces with numerous cytoplasmic extensions
and filopodia. There is not much difference for the NIH3T3 cells
grown on pure Ti and TZHCNSS samples, since cells on both sam-
ples have connected to other cells and tiled on the surfaces.
Fig. 6 demonstrates the implantation of TZHCNSS BMG and pure
Ti samples after 1 month implantation into the mandibles of
beagle dogs [28]. It can be observed from Fig. 6 that after one
month implantation there is no inflammation observed around
the operation sites. And no bone resorption could be observed for
both pure the Ti sample and TZHCNSS samples. There is no signif-
icant difference between two samples.
Both the pure Ti and TZHCNSS samples are well integrated with
the bone tissue. New bone was formed around the implants. The
EDS analysis also proved that the bones integrated well with both
the pure Ti and TZHCNSS samples, the gap between the bone tissue
and metallic samples are no more than 5 lm.

Fig. 5. SEM images of L929 and NIH3T3 cells on different sample surfaces after 4 days of incubation. (a) L929 cell on pure Ti; (b) NIH3T3 cell on pure Ti; (c) L929 cell on
TZHCNSS; (d) NIH3T3 cell on TZHCNSS.

Fig. 6. Implantation of TZHCNSS BMG and pure Ti samples (a) BMG sample; (b) representative X-ray images for the implants and (c, d) representative histological images
stained by methylene blue after 1 month implantation. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this
article.)
 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20 7

Table 3
Summary of biomedical Zr-based BMG systems and their mechanical properties.

Chemical composition (at.%) Preparation method Critical Compressive Young’s Vickers Reference
diameter/ fracture modulus hardness (Hv)
thickness (mm) strength (rf) (kg mm 2)
(MPa)
Zr52.5Al10 Ti5Cu17.9 Ni14.6 (BAM-11) Arc-melting/copper mold casting 7 1700 (tensile 90 590 [36]
yield strength)
Zr61Cu17.5Ni10Al7.5Si4 Melt spinning — 1800 — 510 (5 GPa) [37]
Zr60Cu22.5Pd5Al7.5Nb5 Arc-melting/copper mold casting — 1720 82 — [38]
Zr60Ti6Cu19Fe5Al10 Arc-melting/copper mold casting — 1652 70 — [35]
Zr60Nb5Cu20Fe5Al10 Arc-melting/copper mold casting — 1795 72 — [35]
Zr60Nb5Cu22.5Pd5Al7.5 Arc-melting/copper mold casting — 1724 70–85 — [39]
Zr61Ti2Cu25Al12 Arc-melting/copper mold casting 6 — 83 — [40]
(ZrxCu100 x)80(Fe40Al60)20 (x = 68–77) Arc-melting/copper mold casting 13 when x = 72.5 1560–1690 — 521–563 [41]
(yield strength)
Zr100 x y(Cu5/6Ag1/6)xAly (x = 38, 40, 42, 44, 46, 48, Arc-melting/copper mold casting 20 1900–1916 — — [42]
50 and 52 at.% and y = 6, 7, 8 and 9 at.%) alloys
Zr56Al16Co28 Arc melting/arc-tilt-casting, arc 18 1830 (tensile 83 — [43,44]
melting/single roller quenching strength)
Zr65Pd17.5Fe10Al7.5 Arc-melting/copper mold casting 6 Around 1500 — 422 [45]
Zr65Pd12.5Ag5Fe10Al7.5 Arc-melting/copper mold casting 6 Around 1500 — 411 [45]
(Zr0.62Cu0.23Fe0.05Al0.10)100 xAgx (x = 0, 1, 3, 5, 7) Arc-melting/copper mold casting 3–10 (10 when 1640–1720 68–75 — [46],
x = 3) (1720 when
x = 3)
Zr60.14Cu22.31Fe4.85Al9.7Ag3 Arc-melting/copper mold casting 10 1720 ± 28 82 ± 1.9 [47]
Zr60 + xTi2.5Al10Fe12.5 xCu10Ag5 (at.%, x = 0, 2.5, 5) Arc-melting/copper mold casting — 1450–1580 70–78 443–460 [48]
Zr55Cu30Ni5Al10 — — 1830 — 416 ± 10 [49]
Zr46Cu37.6Ag8.4Al8 Arc-melting/copper mold casting — 2158 92 554 [31]
Zr51.9Cu23.3Ni10.5Al4.3 Arc-melting/copper mold casting — 1997 102 550 [31]
Zr51Ti5Ni10Cu25Al9 Arc-melting/copper mold casting — 1962 100 542 [31]
Zr62.5Al10Fe5Cu22.5 Arc-melting/copper mold casting 6 1700 80 459 (4.5 GPa) [14]

3. Zr-based bulk metallic glasses for biomedical implants and
devices
3.1. Mechanical properties of biomedical Zr-based BMGs
During biomedical application services under different physio-
logical conditions, biomaterials would experience loadings from
surrounding tissues, blood vessel walls and bones, which pose
requirements on their mechanical properties. As shown in Table 3,
the biomedical Zr-based BMGs have been featured with a high hard-
ness that is about twice to three times of that for conventional crys-
talline biomedical 316L SS, Ti alloys and Zr alloys, and high yield
strength that is considerably higher than that of those above men-
tioned conventional crystalline metallic biomaterials. Fig. 4(B)
shows the compressive stress–strain curves of three Ni-free Zr-
based BMGs. It can be seen from Fig. 4(B) that all BMGs exhibit a high
yield strength over 1300 MPa, and fracture strength over 1600 MPa
[35]. It is interesting to note that the three BMGs also exhibit a con-
siderably large plastic strain. In addition, the elastic strains around
2% with low modulus of 70–80 GPa were obtained. The modulus is
lower than that of 316 L stainless steel (about 200 GPa) and Ti–
6Al–4V alloy (110–125 GPa). The high strength of the Zr-based
BMG greatly enables the production of biomaterials with thinner
struts for cardiovascular stents, which benefits its deliverability
and reduces the rate of restenosis. Compared to conventional 316L
SS stents, biomedical Zr-based BMG stents would require only one
third of the cross-section of the strut and would have more than five
times the deflection [9]. And the BMG bone screws could have a thin-
ner shank and deeper threads thus yielding greater holding power to
the fracture bones. It is also worth mentioning that high elastic limit
of about 2% and low Young’s modulus indicated that the elastic
deformation with external loading will be facilitated and would con-
sequently distribute stresses more uniformly than current materi-
als, minimizing stress concentrations, reducing stress shielding
effects, and thus achieving faster healing rates.
3.2. Corrosion behavior of biomedical Zr-based BMGs
The corrosion behavior of the biomedical Zr-based BMGs has
been investigated in various physiological solutions, including
PBS [50], Hank’s solution [37], 0.9% NaCl saline solution [51], Ring-
er’s solution [9], artificial saliva solution [52], and SBF solutions
[47]. The results demonstrated that in comparison with conven-
tional crystalline 316L stainless steel, Zr and Zr-based alloys and
Ti and Ti-based alloys, the BMGs show evidently a lower passive
current density, much higher pitting potential, suggesting that
the passive films formed on the Zr-based BMGs are more protec-
tive than on the above mentioned control groups, indicating their
enhanced corrosion resistance behavior [38,39]. The high corrosion
resistance of the biomedical Zr-based BMGs can be attributed to
the formation of the passive films, mainly composed of ZrO2, on
the surface of the alloy. Adding Nb [53,54] and Ag [55] are benefit
for the corrosion resistance, especially enhanced the corrosion
resistance against pitting corrosion.
3.3. Biocompatibility of biomedical Zr-based BMGs
For a candidate biomaterial to be used in clinical applications,
excellent biocompatibility is an essential property in order to avoid
any adverse effect in human body. Many studies have investigated
8 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20

Fig. 7. The morphologies of MG63 cells cultured on (a) Zr60.14Cu22.31Fe4.85Al9.7Ag3 BMG stained with Hochest-33258; (b) Zr60.14Cu22.31Fe4.85Al9.7Ag3 BMG stained
with FITC–phalloidin; (c) Zr60.14Cu22.31Fe4.85Al9.7Ag3 BMG stained with both Hochest-33258 and FITC–phalloidin; (d) pure Zr stained with both Hochest-33258 and FITC–
phalloidin; (e) Ti6Al4V alloy stained with both Hochest-33258 and FITC–phalloidin; and (f) positive control for 3 days.

the biocompatibility of Zr-based BMGs via both in vitro cell
response and in vivo animal implants. And results have shown that
Zr-based BMGs showed better biocompatibility than the conven-
tional crystalline 316L stainless steel Zr and Zr-based alloys and
Ti and Ti-based alloys, for both the in vitro cell culture (MTT/
CCK8 assay and cell morphology observations), including the
mouse pre-osteoblast cells MC 3T3 E1 [55,56], murine fibroblast
cells (L929 cell and NIH3T3 cell) [35,38,39,52], human umbilical
vein endothelial cells [40] and MG63 human osteoblast-like cells
[40,57], macrophage cells [9], human aortic endothelial cells
(HAECs) and human aortic smooth muscle cells (HASMCs), and
in vivo rabbits implantations [35]. Fig. 7 demonstrates the mor-
phologies of MG63 cells cultured on Zr-based BMG, crystalline
pure Zr, and crystalline Ti6Al4V alloy for 3 days. It can be seen from
Fig. 7 that a large number of labeled cells are attached to and
spread out on these surfaces. The free-growing control cells have
a thin, thread-like shape (please refer to Fig. 7(f)). The cells cul-
tured with the three different samples (Fig. 7(c–e)) exhibited an
obviously larger footprint area in contrast to the free-growing
ones: actin filaments are clearly seen aligned in a parallel direction,
and focal adhesion plaques (green) are distributed at the cell
periphery, identified as the extremities of the actin filaments. No
other obvious differences in adhesion morphology were found
between the three metals [47]. Fig. 8 shows the animal study
results after implantations with ZrCuAlAg BMG and Ti–6Al–4V
implants. From Fig. 8, we can see that during the whole experiment
period, no multinucleated giant cell and lymphocytes can be found
at the bone area around the implants, meaning that no inflamma-
tion or osteonecrosis occurred. New bone was formed around the
implants. After implantation for 4 weeks, gaps between bone tissue
and metallic sample are very small (6 lm and 8 lm for ZrCuAlAg
BMG and Ti–6Al–4V alloy, respectively) (Fig. 8j and m). After
implantation for 8 and 12 weeks, no gap can be observed between
the bone tissue and metallic implant samples. Both implant
samples are well integrated with bone tissue [58].
4. Fe-based bulk metallic glasses for biomedical implants and
devices
4.1. Mechanical properties of biomedical Fe-based BMGs
Fe-based BMGs have very low costs compared to Ti-based or
Zr-based BMGs, making them quite attractive for any large-scale
biomedical applications. Moreover, they also have reasonably good
glass forming ability (GFA) and can be easily prepared by tradi-
tional Cu-mold casting/cooling methods. Since the first synthesis
of Fe-based BMG in Fe-Al-Ga-P-C-B system in 1995 [59], a variety
of Fe-based BMG have been developed, including Fe-(Zr,Hf,Nb)-B,
Fe-Co-Ln (lanthanide metal, such as Tm, Er)-B, Fe-Ga-(P,C,B,Si) sys-
tems [60]. However, most of these developed Fe-based BMGs are
 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20 9

Fig. 8. The animal study results after implantation for 4 weeks (left column), 8 weeks (middle column), and 12 weeks (right column): (a), (b), (c) radiographs of thighbones
with ZrCuAlAg BMG and Ti–6Al–4V implants after surgery, H&E stained results after implantation: (d), (e), (f) ZrCuAlAg BMG implant and (g), (h), (i) Ti–6Al–4V implant, and
SEM images of implants and bone interface, and the corresponding EDS analysis with the elemental distribution of the white line: (j), (k), (l) ZrCuAlAg BMG implant; and (m),
(n), (o) Ti–6Al–4V implant.

soft magnetic materials as functional and structural materials, for
example, power inductor and soft magnetic cores and not suitable
for biomedical applications considering their magnetic properties.
In clinical, MRI diagnosis is inhibited with the presence of magnetic
implants in body because they become magnetized in the intense
magnetic field of the MRI instrument, which may produce image
artifacts and therefore prevent exact diagnosis [61,62]. To decrease
the artifacts, medical devices with low magnetic susceptibility are
required.
Nonmagnetic Fe-based BMGs were firstly developed by Pon-
nambalam V et al. in 2003 and are called as ‘‘amorphous steel”
[63] because their composition are similar to that of stainless steel,
i.e. both of the stainless steel and amorphous steel contain Fe, C, Cr,
Mo elements. The chemical composition, mechanical properties of
reported Fe-based BMGs for biomedical application purpose are
listed in Table 4. Table 4 demonstrated that amorphous steels have
glass-forming ability high enough to form single-phase glassy rods
with diameters reaching 16 mm. It is not surprising that a variety
of Fe-based BMGs were being investigated as future biomaterials
considering their excellent corrosion, wear resistance and rela-
tively low material cost. Previous studies have shown that the vick-
ers hardness of Fe-based BMGs in the range of 1200–1800 MPa and
tensile fracture strengths of at least 3000 MPa, values that far
exceed those reported for state-of-the-art steel alloys, and Fe-
based BMGs have better MRI compatibility compared to 316L SS
[64]. Fig. 4(C) shows the uniaxial compressive true stress–strain
curves for four Fe–Cr–Mo–P–C–B BMGs. It can be seen from
Fig. 4(C) that the current materials exhibit high yield stresses
10 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20

Table 4
Summary of biomedical Fe-based BMG systems and their mechanical properties.

Chemical composition (at.%) Preparation method Critical diameter/ Compressive fracture Young’s Vickers hardness (Hv) Reference
thickness (mm) strength (rf) (MPa) modulus (kg mm 2)
Fe41Co7Cr15Mo14C15B6Y2 Arc-melting/copper 16 3500 — 1253 [66,67]
mold casting
Fe63Mo14C15B6Er2 Arc-melting/copper 3 4000 204 1122 (11 GPa) [68]
mold casting
Fe55Cr8Mo14C15B6Er2 Arc-melting/copper >4 — 209 1122 (11 GPa) [68]
mold casting
Fe49Cr15Mo14C(13 + x)B(8-x)Er1 Arc-melting/copper 3–6 4040–4140 210–220 — [69]
(x = 2, 4, 5 and 6) mold casting
(Fe0.9Co0.1)58.5Cr6Mo14C(15 + x)B(6-x) Arc-melting/copper 2–4 4070–4100 200 — [69]
Er0.5 (x = 3 and 4) mold casting
Fe48Cr15Mo14C15B6Er2 Arc-melting/copper 12 4200 213 1122 (11 GPa) [68]
mold casting
Fe70B20Si10 Melt spinning — 2500 — 714 (7 GPa) [37]
(Fe44Cr10Mo12.5Mn11C15B6Y1.5) Arc-melting/copper 2–5 — — — [64]
100 xMnx (x = 0, 2, 4, 8) mold casting
Fex (x = 63–71) Cry (y = 0–3) Moz (z = 5– Arc-melting/copper 2.5–3 3150–3550 176–183 845–974 [65]
12) P12C10B2 mold casting

and fracture strengths reaching 2.9 and 3.5 GPa, respectively, and
high plastic strains up to 3.6%. The ductility of amorphous steels,
or Fe-based BMGs in general, can be significantly enhanced by
properly tuning the alloy compositions [65].
4.2. Corrosion behavior of biomedical Fe-based BMGs
It is well known that conventional biomedical stainless steels
(3l6L SS and 304 SS) are usually prone to localized attack and Ni
ion release in long-term applications due to their poor corrosion
resistance because of the aggressive biological effects [70]. The
developed Fe-based BMGs have higher pitting potential values
and lower corrosion current density values both in Hank’s solution
and in artificial saliva solution and have quite lower ion releasing
than that of 316L SS [67], together with good biocompatibility
in vitro [71]. Shahverdi et al. studied the corrosion behavior of
Fe55-xCr18Mo7B16C4Nbx (x = 0, 3, and 4 at.%) amorphous ribbon
s in Ringer’s solution [72], and the linear polarization and EIS mea-
surements indicated that the Fe51Cr18Mo7B16C4Nb4 possesses
larger polarization resistance value than that of 316L SS and Ti-
6Al-4V.
4.3. Biocompatibility of biomedical Fe-based BMGs
biocompatibility and MRI compatibility before its application in
the biomaterials markets.
5. Biodegradable bulk metallic glasses designed for temporary
implants and devices
Besides the joint replacements that need permanent prosthesis
implantation in the human body, there are many other clinical
cases, such as bone fracture, cardiovascular diseases, in which
the temporary implant materials are needed. The fixation or
mechanical support are temporarily needed during the healing
process of the injured or pathological tissue, and after that, the
implants accomplish their mission and will no longer function in
human body. In this case, biodegradable materials are the optimal
choice as these materials do their job while healing and new tissue
forming occur and degrade in the human body thereafter.
As summarized in Table 5, the biodegradable BMG family
includes members such as Ca-based BMGs, Mg-based BMGs, Sr-
based BMGs and Zn-based BMGs. Their fabrication methods, phys-
ical and mechanical properties are summarized in Table 5 as well.
In the following paragraphs, we will separately discuss and thor-
oughly review the currently developed biodegradable BMG
systems.

As mentioned above, the enhanced mechanical properties and
corrosion behavior guarantee the biocompatibility of Fe-based
BMGs as future biomaterials. It has been reported that Fe-based
BMGs exhibited better biocompatibility for the in vitro murine
fibroblast cells (L929 cell and NIH3T3 cell) culture (MTT/CCK8
assay and cell morphology observations) [71]. Cell number grows
quickly during the 4-day culture period for all groups, and there
is no obvious difference between negative group and experimental
groups. Most cells appear elongated in a spindle shape and become
longitudinally aligned at high cell densities. High cell viability
value of Fe based BMGs approaching to the negative control group
could be explained by the protective effect of the compact oxide
film, avoiding metal ion releasing in the biofluid [71]. In addition,
previous study has demonstrated Fe-based BMGs have better
MRI compatibility compared to 316L SS [64], and this would make
it promising candidate for biomedical materials and therapeutic
devices used under MRI bio-imaging and diagnostics environment.
Further in vivo and pre-clinical case studies are needed to verify the
5.1. Biodegradable Mg-based BMGs
Crystalline magnesium alloys have attracted considerable
attention as potential implant materials in recent years [92,93],
series crystalline magnesium alloys, including Mg-Zn [94–96],
Mg-Sr [97,98], Mg-Ca [99,100], Mg-RE [101,102] systems have
been designed and developed for biomedical applications. How-
ever, the development and deployment of biodegradable magne-
sium alloys faces some practical challenges. First, a much higher
inherent strength would be required of such an alloy since an
implant’s strength would naturally deteriorate gradually during
the corrosion/degradation process. Next, pitting corrosion, result-
ing in surface defects, would likewise lead to the quick loss of
the magnesium alloy’s strength. Third, most current magnesium
alloys have fast degradation rates, exceeding rates for bone heal-
ing. Finally, the release of hydrogen and localized alkalization
caused by the fast corrosion may also do harm to the surrounding
tissues.
 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20 11

Table 5
Summary of biodegradable BMG systems and their mechanical properties.

BMG system Chemical composition (at.%) Preparation method Critical diameter/ Compressive Young’s Vickers Reference
thickness (mm) strength (MPa) modulus hardness (Hv)
(GPa)
Ca based Ca65Mg15Zn20 Induction-melting/copper mold 6 364a 20a 1.42 [73–75]
casting
Ca57.5Mg15Zn27.5 Induction-melting/copper mold 4 — 36.5 0.9 [76]
casting
Ca55Mg17.5Zn27.5 Induction-melting/copper mold 4.5 — 36 0.9 [76]
casting
Ca52.5Mg20Zn27.5 Induction-melting/copper mold 2.5 — 39 1.4 [76]
casting
Ca52.5Mg17.5Zn30 Induction-melting/copper mold 0.9 — 44 1.4 [76]
casting
Ca52.5Mg22.5Zn25 Induction-melting/copper mold 1.0 — 43 0.8 [76]
casting
Ca50Mg20Zn30 Induction-melting/copper mold 1.2 — 46 0.7 [76]
casting
Ca65Li9.96Mg8.54Zn16.5 Induction-melting/copper mold 5 530 23.4 1.35 [77]
casting
Ca48Zn30Mg14Yb8 Induction-melting/copper mold 2 600 31.9 — [89]
casting
Ca20Mg20Zn20Sr20Yb20 Induction-melting/copper mold 4 370 19.4 — [79]
casting
Mg based Mg65Cu25Gd10 Melt Spinning — 800 — 2.5 [37]
Mg67Cu25Y8 Melt spinning — 800 — 2.5 [37]
Mg60Cu29Y10Si1 Induction-melting/copper mold 2.6 — 66b 4b [80]
casting
Mg80 xCa5Zn15 + x (x = 5–20) Induction-melting/copper mold 1–4 700 47.6– 2.16 [81]
casting 48.2
Mg96 xZnxCa4 (x = 30, 25) Induction-melting/copper mold 2–5 930 when x = 30 and — — [82]
casting 830 when x = 25
Mg67Zn28Ca5 Melt-extraction 100 lm thin 817 — 2.16 [83]
wires
Mg69Zn27Ca4 Induction-melting/copper mold 1.5 550 — — [84]
casting
Mg66Zn30Ca4-xSrx (x = 0, 0.5, 1, Induction-melting/copper mold 4–6 787–848 48.5– 2.45–2.51 [85]
and 1.5 at.%) casting 49.4
Mg66-xZn30Ca4Ndx (x = 0, 0.5, 1, Induction-melting/single roller 25–35 lm — — — [86]
1.5at.%) spinning
Mg66Zn30 xCa4Agx (x = 0, 1, and Induction-melting/copper mold 1–4 780 — 2.35 [87]
3 at.%) casting or melting spinning
Mg66Zn30Ca2Yb2, Mg66Zn30Yb4, Induction-melting/copper roller 40–100 lm 500 (tensile) 35 — [88]
Mg64Zn30Yb6, Mg60Zn30Yb10 spinning
Zn based Zn38Ca32Mg12Yb18 Induction-melting/copper mold 2 640c 36.6c — [89]
casting
Zn40Mg11Ca31Yb18 Induction-melting/copper mold 2 663 — — [78]
casting
Sr based Sr40Mg20Zn15Yb20Cu5 Induction-melting/copper mold 3 408 20.6 — [90]
casting
Sr60Mg18Zn22 Induction-melting/copper mold 3 — 19.7 — [91]
casting
Sr60Li5Mg15Zn20 Induction-melting/copper mold 3 — 18.4 — [91]
casting
a
Average data at various strain rates.
b
Estimated date from Fig. 10 in [80].
c
Calculated from Fig. 3 in reference [89].

Recent research into Mg-based BMGs, however, has found that
they have higher strength and lower elastic moduli than pure Mg
and conventional Mg alloys. Fig. 9(A) demonstrates the compres-
sion properties of Mg66Zn30Ca4 and Mg70Zn25Ca5. It can be
observed form Fig. 9(A) that the fracture strength rf for
Mg70Zn25Ca5 and Mg66Zn30Ca4 samples is (565.8 ± 23.2) and
(531.2 ± 22.8) MPa, respectively, which is much higher than that
of pure Mg sample (198.1 ± 4.5) MPa [103]. Studies of the corrosion
behavior, cellular response and tissue response of Mg-Zn-Ca BMGs
by Zberg B et al. [104] and Gu et al. [103] demonstrate that Mg-Zn-
Ca BMGs present more uniform corrosion morphology than con-
ventional crystalline Mg alloys, have much lower corrosion rates,
and show higher cell viability than conventional crystalline pure
Mg. Fig. 10 shows the morphology of (a–c) L929 and (d–f) MG63
cells cultured on (a, d) as-rolled pure Mg, (b, e) Mg66Zn30Ca4
and (c, f) Mg70Zn25Ca5 samples for 5 days. From Fig. 10, it can
be seen that for the as-rolled pure Mg sample, a few cells are
observed on the surface and unhealthy cells with round shape
can be seen after 5 days culture for the two experimental cell lines.
For Mg66Zn30Ca4 and Mg70Zn25Ca5 BMGs, the number of cells
adhered on the surface are higher than crystalline pure Mg, and
healthy cells with elongated or spindle morphologies are observed.
In addition, Fig. 11 demonstrated the animal studies of Mg-based
glass (a, c) in comparison with a crystalline Mg alloy reference
12 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20
Fig. 9. (A) Compression properties of Mg66Zn30Ca4 and Mg70Zn25Ca5. (B) Stress-strain curves of Ca47Mg19Zn7Cu27 BMG. (C) Stress-strain curve of
Sr40Mg20Zn15Yb20Cu5 BMG. (D) Stress–strain curves of Zn38Ca32Mg12Yb18 BMG after immersion in Hank’s solution for various times.
sample (b, d). As shown in Fig. 11, results from animal studies indi-
cate that all samples show a typical fibrous capsule foreign-body
reaction (indicated by white arrows), while only the crystalline
samples (implanted discs indicated by dashed lines) show pro-
nounced hydrogen evolution (area between discs and fibrous cap-
sules indicated by black arrows). And no tissue-imprinted
hydrogen gas cavities had formed in the histological preparations
of the Mg-Zn-Ca BMG samples and no inflammatory reactions
were observed [104]. J.D. Cao [105] and co-workers characterized
the Mg65Zn30Ca5 BMG as a potential biodegradable metal. Their
studies demonstrated that confirmed via in vitro corrosion experi-
ment and subsequent chemical analysis of the exchanged media
solution, the amorphous alloy exhibited a slower corrosion rate
and released Mg ions into the media at approximately half the rate
of a crystalline Mg reference sample. Although both types of mate-
rials had an influence on the L929 cell viabilities over 72 h culture
period, the viabilities remained relatively high, thereby indicating
that they are capable of supporting cellular activities. However,
direct contact with the samples created regions of minimal cell
growth around both amorphous and crystalline samples, and no
cell attachment was observed.
Yu H-J et al. [88] achieved significantly improved ductility for
Mg-based BMGs under bending and tensile loading through minor
alloying with the rare-earth element ytterbium (Yb) recording a
plastic strain of about 0.5% after 2% and 4% Yb was added into
MgZnCa glasses. As an additional benefit, the in vitro biocompati-
bility of Mg-based BMGs was also improved by the Yb-alloying, a
finding confirmed by indirect cytotoxicity and direct cell adhesion,
extension, and proliferation assays [88]. In order to make it easier
to make medical devices, such as woven stents, from Mg-based
BMGs, Zberg B et al. [83] produced wires with very good surface
quality via a melt-extraction setup which show extended homoge-
neous plastic deformation in tensile tests.
5.2. Biodegradable Ca-based and Sr-based BMGs
It is well known that pure metals calcium and strontium are so
active that they can react violently with water generating hydro-
gen gas and hydroxides. As a result, it is very hard to gain stable
crystalline calcium and strontium alloys. However, amorphous cal-
cium and strontium BMGs have nobler properties due to their
unique amorphous structure. According to this, it is easy to under-
stand that for biomedical applications, the only way to develop cal-
cium and strontium based alloy is to form amorphous alloys.
5.2.1. Biodegradable Ca-based BMGs
Li et al. [77] reported development of a class of CaLi-based
BMGs, a new kind of glassy metallic plastic, which includes multi-
ple valuable properties, such as ultralow density (<2 g/cm3). Simi-
lar to conventional glassy polymers, CaLi-based BMGs show
polymer-like thermoplastic formability along with excellent
plastic-like deformability and can be elongated, compressed, bent,
and imprinted near room temperature [106]. Jiao W et al. [89] fab-
ricated a Ca-based BMG with composition of Ca48Zn30Mg14Yb8
with a low Young’s modulus of 31.9 GPa and high fracture strength
of 600 MPa. Fig. 9(B) shows the stress-strain curves of
Ca47Mg19Zn7Cu27 BMG. From Fig. 9(B), we can see that at room
temperature, an as-cast amorphous sample was loaded to 2%
elastic strain and then exploded into powder. During compression
at 110 °C, 120 °C, and 130 °C, yielding occurred and the flow stress
decreased during plastic deformation [107].
Series of Ca-Mg-Zn BMGs were developed by low-pressure die
casting [76]. It was observed that both the critical casting size
and the rate of corrosion of the alloys were dependent on compo-
sition. The corrosion morphology on the Ca-BMG was not typical of
that observed in crystalline alloys where localized pitting and
microstructural-related (i.e., intergranular or intermetallic driven)
 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20
Fig. 10. The morphology of (a–c) L929 and (d–f) MG63 cells cultured on (a, d) as-rolled pure Mg, (b, e) Mg66Zn30Ca4 and (c, f) Mg70Zn25Ca5 samples for 5 days.
attack is expected to be dominant. Instead, the corrosion morphol-
ogy consistently revealed a damage form that can be described as
incongruent dissolution, similar in form to dealloying. Wang et al.
[75] evaluated the feasibility of Ca65Mg15Zn20 BMG for potential
skeletal applications by animal tests and found that although this
Ca-based BMG degrades fast in vitro, there was no obvious inflam-
mation reaction at the implantation site [108]. Although these Ca-
based BMGs show great potential as novel biodegradable metals,
the rapid rates of dissolution in biocorrosion environments due
to the inherently reactive nature of Ca (even more reactive than
Mg) may limit their specific applications as biomaterials. In an
effort to improve the corrosion resistance of metal materials, two
different strategies are usually applied, i.e. surface treatment and
alloying method (adding alloying elements into the master metals
or alloys). Different kinds of biodegradable thin films, including
fluoroalkylsilane (FAS) coating, pure Fe film and (Fe + FAS) bilayer,
were introduced on the surface of Ca-Mg-Zn based BMG and has
reported to reduce its degradation rate significantly [109]. For
the alloying method, considering that BMGs and high entropy
alloys (HEAs) both have unique properties that conventional met-
als and alloys are unlikely to match and the fact that an amorphous
phase can be easily formed in HEAs, the research and development
of new types of alloys that combine BMG and HEA concepts
together would be of great importance for future novel material
13
studies. Ca20Mg20Zn20Sr20Yb20 high entropy BMG alloy was
developed and results showed that both the mechanical properties
and corrosion behavior of the Ca-Mg-Zn amorphous alloy were
obviously enhanced after adding the alloying elements Sr and Yb
and further formed high entropy amorphous structures. In addi-
tion, in vitro and in vivo studies showed that the Ca20Mg20Zn20S-
r20Yb20 high entropy BMG could stimulate and promote
osteogenesis and new bone formation [79]. Fig. 12 shows MG 63
cell staining at 3 days in the negative control group and in cells cul-
tured in series of HE-BMG extracts. It can be observed that healthy
morphologies of MG63 cells, polygon or spindle, were well spread
and extended completely in both series of CMZSY HE-BMG extracts
experimental groups and negative control groups. Fig. 13 demon-
strates the histology of cross-sections of the distal femora and dia-
physeal region of the mice. From Fig. 13, it can be seen that no
inflammation or osteonecrosis was found at the bone area around
the implants. The histological observations at 4 weeks after
implantation show that the bone thickness around the implanted
CMZSY HE-BMG is greater than that of normal bone (yellow arrows
in Fig. 13), which is consistent with the radiographs and micro-CT
results. The new bone at the inner edge of the cortical bone can be
clearly observed (black arrows in Fig. 13). There is no new bone
formation around the wound area where no implants were embed-
ded in the control groups [79].
14 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20

Fig. 11. Animal studies of Mg-based glass in comparison with a crystalline Mg alloy reference sample. Glassy Mg60Zn35Ca5 (a, c) and crystalline Mg alloy reference (WZ21)
(b, d) in two types of porcine abdominal tissue (muscle after 27 days (a, b) and subcutis after 91 days (c, d) of implantation).

Fig. 12. Cell staining at 3 days in the negative control group and in cells cultured in series of HE-BMG extracts. (a) Negative control group; (b) 5% HE-BMG extract; (c) 10%
HEBMG extract; (d) 25% HE-BMG extract; (e) 50% HE-BMG extract; (f) 100% HE-BMG extract. 200; the scale bar represents 100 lm.

5.2.2. Biodegradable Sr-based BMGs
Strontium-based BMG systems have attracted great interest for
their potential in biomedical applications. Studies have shown that
strontium can inhibit bone resorption and stimulate bone forma-
tion [110]. Sr-based drug treatments for osteoporosis, such as Pro-
telos (Strontium ranelate) [111] can reduce the risk of fracture in
patients after one year of treatment and inhibit osteoclast activity
and stimulate osteoblast proliferation [112]. Strontium, calcium
and magnesium are in the same group of periodic table and the
physiological distribution of Sr is similar to that for Ca, with 99%
of the element being stored in bone [113]. Under normal condi-
tions, the bone strontium/calcium ratio varies between 1:1000
 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20
Fig. 13. Histological observation of cortical bone by light microscopy with H&E staining: (a, c) Normal bone and the bone marrow cavity; (b, d) CMZSY HE-BMG rod in the
femur of a mouse 4 weeks after implantation.
and 1:2000 with the highest concentration appearing in newly
formed bone [114] suggesting its potential value for biomaterials.
However, as we discussed before, due to its excessively active
property, the design and development of conventional crystalline
pure strontium and strontium based alloys for biomedical applica-
tion is infeasible. In order to overcome this situation, researchers
have investigated Sr-based BMGs for their potential use in bone
implants and thus in 2009 Zhao K et al. [91] reported a family of
Sr-based BMGs with good glass-forming ability and many unique
properties. These Sr-based BMGs had ultralow glass transition
temperature Tg, low elastic moduli, wide supercooled liquid
regions, and showed excellent plastic-like deformability at low
temperature, similar to that for CaLi-based BMGs. Moreover, these
Sr-based BMGs demonstrated tunable degradation behavior and a
corrosion rate that could be controlled simply through minor
alloying. Li et al. [90] investigated the bio-corrosion and biocom-
patibility of Sr40Mg20Zn15Yb20Cu5 BMG. And Fig. 9(C) shows
the stress-strain curve of Sr40Mg20Zn15Yb20Cu5 BMG. From
Fig. 9(C), it can be observed that the fracture strength rf for
Sr40Mg20Zn15Yb20Cu5 BMG is (408.2 6 20.0) MPa [90]. The
in vitro cell culture studies demonstrated that most of the MG63
cells that were cultured in the Sr40Mg20Zn15Yb20Cu5 BMG
extraction medium were flattened, had polygonal configuration
and dorsal ruffles, and were well attached to the substrate by
cellular extension, indicating their healthy status [90]. The combi-
nation of increased mechanical strength, greater corrosion
resistance, and excellent biocompatibility make it as potential
material for biodegradable orthopedic implant applications.
5.3. Biodegradable Zn-based BMGs
Zinc is an essential element for human beings, serving as a
cofactor in all six classes of enzymes [115] as well as several
classes of regulatory proteins [116], and is the second most abun-
dant transition metal element in human body [117]. Zinc has also
15
been widely used as an alloying element in Mg-, Ca-, and Sr- based
BMGs, which have great potential for use as biodegradable
implants. Recently, crystalline pure Zn and Zn-based alloys, such
as Zn-X (Mg, Ca, Sr) alloys have been investigated as potential
biodegradable materials and results demonstrated that pure Zn
and Zn-based alloys have great potential orthopedic and cardiovas-
cular applications [118–121].
Considering that, biodegradable Zn-based BMGs were devel-
oped by Jiao W and co-workers, who further studied their mag-
netic susceptibility, mechanical properties, corrosion behavior
and cytocompatibility [78,89]. Aiming to develop a class of Zn-
based BMGs as new category of bone repair and fixation materials,
Jiao et al. found that a Zn-based BMG with a composition of
Zn38Ca32Mg12Yb18 showed much higher strength (above
600 MPa) than conventional 837 Mg (about 200 MPa) crystalline
materials, with much smaller magnetic susceptibility
(22.3  10 6) than that of commonly used biomedical alloys, and
slower degradation rates than pure Mg. In addition, practically
no hydrogen was generated during the material’s immersion time.
Fig. 9(D) shows the stress–strain curves of Zn38Ca32Mg12Yb18
BMG after immersion in Hank’s solution for various times. As
shown in Fig. 9(D), the Zn38Ca32Mg12Yb18 BMG’s compression
fracture strength showed no obvious decline after 30 days of
immersion in Hank’s solution [89]. This feature of the Zn38Ca32M-
g12Yb18 BMG is clearly superior to Mg–6Zn alloy which exhibits a
large decrease in bending strength resulting from surface defects
such as holes formed during non-uniform corrosion. Cytotoxicity
tests (MTT/CCK8 assay and cell morphology observations) revealed
that this Zn-based BMG showed good cytocompatibility with
MG63 osteoblast cells. Compared to the cell group, the viability
of all cultured in extraction is better than 90%, similar to that of
the negative group. There was no significant difference (p > 0.05)
between MG63 cells cultured in extracts and negative group.
MG63 cells presented healthy elongated spindle shape when cul-
tured on the Zn38Ca32Mg12Yb18 BMG substrate. Whereas MG63
16 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20
cells after incubation on pure Mg substrate showed round shape in
unhealthy or apoptosis state. This further confirms that the Zn-
based BMG has good cytocompatibility with no negative effects
on cell morphology and viability.
6. Future research directions and challenges for BMGs as
potential biomaterials
Although BMGs have great potential as future biomaterials,
there are considerable challenges associated with the development
of biomedical BMGs. Firstly, the limited critical sizes of BMGs
would hinder the design of biomedical devices using BMGs. Sec-
ondly, the toxic elements (such as Ni, Be) that commonly exit in
many BMG systems may bring the long term biosafety concerns.
Besides, structural relaxation and the associated embrittlement
in some BMG systems may occur when processing the BMGs via
annealing treatments.
Fig. 14 illustrated the future research directions and challenges
for BMGs as potential biomaterials. In order to further meet the
various requirements for clinical applications, the future studies
for BMGs as potential biomaterials are suggested to be focused
on the following aspects: overcoming the brittleness, increasing
the GFA thus obtaining BMGs with larger sizes, removing/reducing
toxic elements, and surface modifications, as schematically illus-
trated in Fig. 14.
6.1. BMG composites
Although BMGs exhibit high strength and show substantial frac-
ture toughness, some of them lack ductility and fail in an apparently
brittle manner in unconstrained loading geometries (such as in ten-
sile manner) [122]. The potential for catastrophic failure associated
with the rapid propagation of shear bands is a concern for the utiliza-
tion of BMGs in biomedical applications. As mentioned above, the
strain localization and propagation is particularly problematic under
tensile stress states where failure may occur along a single shear
plane with very limited measurable plastic deformation [123]. For
instance, some BMGs exhibit significant plastic deformation in com-
pression or bending tests, but with negligible plasticity (<0.5%
strain) in uniaxial tension. To overcome brittle failure in tension,
BMG–matrix composites have been introduced [124,125]. In BMG
Fig. 14. Illustration of future research directions and challenges for BMGs as potential biomaterials.
composites, the second-phase particles can act both as initiation
sites for shear bands and as barrier to shear band propagation which
result in a dramatic increase in a number of shear bands, and in turn
allows for significant ductility [126,127]. Various approaches have
been taken to fabricate BMG composites and they can be divided into
two groups. One is precipitation of a quasicrystalline phase from the
amorphous matrix during annealing [128,129], the other is incorpo-
rating a ductile phase in the amorphous matrix [130–132]. For
example, The Zr38Ti17Cu10.5Co12Be22.5 BMG/porous tungsten
phase composite prepared by pressure infiltration shows greater
plastic deformation (30% strain) and flow stress than the unrein-
forced metallic glass and the pure W [133]. Future studies need to
focus on their performances under physiological circumstances,
including bio-mechanical properties, bio-corrosion behavior and
biocompatibility evaluations.
6.2. BMG foams
As mentioned above, the lack of macroscopic plasticity is con-
sidered the Achilles’ heel of BMGs and has prevented wide-
spread proliferation of BMGs as biomedical materials. Besides
BMG composite, fabricating BMG foams is another solution to
overcome this critical defect of BMGs. It has been reported that
when BMGs are used in geometries where one dimension is below
about 10 times its critical crack length (1 mm for a medium range
Zr-based BMG), they exhibit significant bending plasticity. This fea-
ture and other size effects have been widely explored in foams to
design overall plasticity [134,135]. On the other hand, previous
studies have demonstrated that porous structures with suitable
pore sizes (200–500 lm) are favorable for cell attachment, prolif-
eration and differentiation [136,137]. Thirdly, the strength and
the Young’s modulus of the porous materials can be adjusted
through the adjustment of the pore size and the porosity in order
to match the requirement of bone repairs as orthopedic implants.
Thus, the BMG foams may offer unique properties in biomedical
implants.
Porous bulk metallic glass Zr57Nb5Cu15.4Ni12.6Al10 (Vit106)
has been fabricated by low-pressure infiltration of carbon micro-
spheres and by casting the alloy into a bed of leachable salt (BaF2
has been chosen for its high stability and melting point) that is
subsequently dissolved after solidification [138,139]. And the
 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20
obtained foam structure is macroscopically homogeneous with a
uniform pore size of 212–250 lm and the strength is 100 MPa at
50% strain. In addition, the BMG foams with honeycomb structures
have been fabricated by combination of lithography and thermo-
plastic forming (TPF) fabrication, and the deformation made of a
BMG honeycomb can be altered from brittle to ductile through
varying the ratio of ligament length to ligament thickness and a
0.2% increase in density doubles strength and energy absorption
[140]. Considering the above mentioned information, it seems that
the physical and mechanical properties of the porous BMGs are
suitable for the biomedical application requisition. Unfortunately,
however, to the present authors’ knowledge, the physiological
properties of the porous BMGs have not been reported till now.
Future studies need to focus on their performances under physio-
logical circumstances, including bio-mechanical properties, bio-
corrosion behavior and biocompatibility evaluations.
6.3. Removing toxic and noble alloying elements
Many BMGs developed so far contain toxic elements for clinical
applications, such as beryllium [141], nickel [142] etc. The toxicity
of these ions and their release may require further attention, par-
ticularly in the light of recent problems with metal toxic effects
seen with metal on metal articulations. On the other hand, some
BMGs with high GFA usually contain noble metal palladium
[143], which increases the production cost. These two factors
may severely hinder the widespread applications of BMGs in
biomedical applications, thus removing the toxic and noble alloy-
ing elements in BMGs while still keep their high GFA at the same
time is another research direction and challenge for the further
research and development of biomedical BMGs.
6.4. Improving BMG critical sizes
Although it is now possible to fabricate BMGs with diameters of
several centimeters at certain chemical compositions, most of the
Ni-free and Be-free BMGs developed have relatively low GFA so
far, resulting in forming small size samples [38,144], and some of
the amorphous alloys could only form amorphous ribbons with
the thickness of several or ten microns [33,145]. The low GFA
and small sizes of amorphous alloys could not satisfy the require-
ments of future biomedical applications, as most of biomedical
devices are in the geometric sizes of several micrometers to several
centimeters. Therefore, in order to meet the requirements of
biomedical applications, one of the main directions and challenges
of further exploring and developing biomedical BMGs is to enhance
their GFA and critical sizes significantly.
6.5. Surface modification of BMGs
Multiple approaches have been developed to obtain the desired
surface properties of biomaterials, and their mechanical, chemical
and biological properties can be improved selectively using the
appropriate surface treatment techniques while the desirable bulk
attributes of the biomaterials are retained [146]. The proper sur-
face treatment will undoubtedly expand the use of biomaterials
in clinical. Considering on this point, surface modification of BMGs
for biomedical applications is one of the important directions for
the further studies of biomedical BMGs.
The biggest challenge for surface modification of biomedical
BMGs is to choose the proper surface modification method while
the amorphous nature of the substrate is not destroyed during
the modification process. Thus the desirable properties attributed
to the unique amorphous structure of BMGs could be retained dur-
ing the surface modification process.
17
6.5.1. Surface modification of non-biodegradable BMGs
Proper surface treatment can further expand the usage of BMG
alloys in the biomedical fields. For example, many currently devel-
oped non-biodegradable BMGs contain nickel, beryllium, which
would have adverse effects on human health when the content is
over a certain concentration threshold. Besides developing new
BMG systems without these toxic elements, surface modification
can also be considered in order to prevent or reduce the release
of these elements into the human body. Although there are few lit-
eratures about reducing the toxic elements releasing of BMGs by
surface modification, there are many literatures about reducing
the toxic elements releasing of conventional crystalline biometallic
materials, which we can use as references when further studies for
surface modifications of BMGs. For instance, the Tantalum [147],
zirconium nitride [148], titanium nitride [149,150], TiC/Ti
[151,152], diamond-like carbon (DLC) [153,154] coatings that are
applied for the preventing of toxic ions releasing and improvement
of biocompatibility of conventional NiTi alloys can be considered
when further studying and development surface modifications of
biomedical BMGs.
On the other hand, just as conventional bioinert materials, such
as pure Ti and Ti-6Al-4V, non-degradable BMGs are bioinert by
nature and cannot form a bioactive bond with the living bone after
they are implanted in bony sites. Typically, surface modifications
are required in order to prepare a bioactive coating on top of the
BMG surface.
For the surface modification of non-degradable BMGs, we can
consider the methods applied in conventional pure Ti and Ti alloys,
such as sand-blasting, electrochemical treatment (anodic oxida-
tion), sol–gel, alkali treatment etc. [155]. A few surface treatments
of BMGs have been reported in order to improve their physiological
properties and biocompatibility. For instance, Liu’s research group
[156] modified the surface of Zr-based BMGs by using the micro-
arc oxidation technique. A rough and porous oxide layer mainly
containing tetragonal ZrO2 and amorphous SiO2 incorporating
some Ca and P was formed. The Ti- and Zr-based BMGs’ surfaces
have been modified by sandblasting and improved the cell attach-
ment, proliferation, and differentiation, thus effective for improv-
ing implant osseointegration in vivo [157]. Hydrothermal-
electrochemical treatment was employed on Zr-based BMGs
[158], and Ti-based BMGs [159], which resulted in the formation
of a bioactive surface and can accelerate nucleation and growth
rate of apatite on the BMG surfaces.
6.5.2. Surface modification of biodegradable BMGs
For some of the developed biodegradable BMGs, such as Ca-Mg-
Zn BMG systems, their fast corrosion rate in physiological environ-
ments is the limit for their further clinical application. Surface
modification is an effective method for slowing down the corrosion
rate of biodegradable alloys. It has been reported that fluoroalkyl-
silane (FAS) coating, pure Fe film and (Fe + FAS) bilayer were
employed on the surface of Ca60Mg15Zn25 BMG, and the results
revealed that these coatings are quite effective to control the cor-
rosion behavior of Ca60Mg15Zn25 BMG [109]. Other surface mod-
ification methods, such as alkaline heat treatment [160], MgF2
coating [161], microarc oxidation [162,163], which are already
used for biomedical Mg and Mg alloys are recommended for
further studies in biodegradable BMGs’ surface modification.
6.6. Metallic glass coatings
Considering their attractive mechanical, physical and chemical
properties of metallic glass alloys, there has been substantial and
long-standing interest in producing amorphous alloy layers on
conventional crystalline metallic substrates since the 1970s
[164]. The metallic glass coatings can enhance the properties of
18 H.F. Li, Y.F. Zheng / Acta Biomaterialia 36 (2016) 1–20
the substrates, such as the mechanical behavior, wear resistance
and corrosion resistance [165]. However, unfortunately, most of
the reported amorphous alloy coatings are mainly for structural
and engineering applications, and studies on amorphous coating
for biomedical application have not yet been explored. Therefore,
one of the directions of further studies is to utilize the amorphous
alloy coatings onto the existing biomedical implants and devices in
order to enhance the properties of the substrates, such as the
mechanical behavior, wear resistance, corrosion resistance and
biocompatibility.
7. Concluding remarks
BMGs have great potential in biomedical applications ranging
from orthopedic, cardiovascular to dental implants and fillers. To
be specific, as non-degradable BMGs, Ti-based, Zr-based and Fe-
based BMGs with combined excellent mechanical properties and
corrosion resistance can be used as biomedical devices, such as
surgical blades, pacemakers, medical stapling anvils, and mini-
mally invasive surgical devices; and biomedical implants, such as
articulating surfaces, artificial prostheses and dental implants,
which are needed to serve a long time in the severe human body
environments. On the other hand, biodegradable BMGs, including
Mg-based, Ca-based, Zn-based and Sr-based BMGs have great
potential as fracture repair materials (such as intramedullary nee-
dles, bone plates and bone screws) as well as cardiovascular stent
materials, absorbable sutures, fillers around dental implants, and
fillings of bone after cyst/tumor removal in arthroplasty; as they
will degrade gradually in human body after completing their tem-
porary mission (would dissolve completely upon fulfilling the mis-
sion of fixing or supporting) during which arterial/bone
remodeling and healing would occur.
Acknowledgements
This work was supported by the National Basic Research Pro-
gram of China (973 Program) (Grant No. 2012CB619102), National
Science Fund for Distinguished Young Scholars (Grant No.
51225101), National Natural Science Foundation of China (Grant
No. 51431002 and 31170909), the NSFC/RGC Joint Research
Scheme (Grant No. 51361165101), Beijing Municipal Science and
Technology Project (Z141100002814008).
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