controlling the biodegradation rate of magnesium using biomimetic apatite coating

Controlling the Biodegradation Rate of Magnesium UsingBiomimetic Apatite Coating

Yajing Zhang,1,2 Guozhi Zhang,1 Mei Wei2

1 School of Materials & Metallurgy, Northeastern University, Shenyang 110004, China

2 The Institute of Materials Science, University of Connecticut, Storrs, Connecticut 06269

Received 8 January 2008; revised 15 July 2008; accepted 28 July 2008Published online 29 September 2008 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.b.31228

Abstract: Magnesium is light, biocompatible and has similar mechanical properties to

natural bone, so it has the potential to be used as a biodegradable material for orthopedic

applications. However, pure magnesium severely corrodes in a physiological environment,

which may result in fracture prior to substantial tissue healing. Hydroxyapatite (HA) is the

main composition of natural bone. It has excellent bioactivity and osteoconductivity. In this

study, HA coating with two different thicknesses was applied onto the surface of pure

magnesium substrates using a biomimetic technique. The corrosion rate of the surface-treated

substrates was tested. It was found that both types of coatings substantially slowed down the

corrosion of the substrate, and the dual coating was more effective than the single coating in

hindering the degradation of the substrate. Thus, the corrosion rate of magnesium implants

can be closely tailored by adjusting apatite coating thickness and thereby monitoring the

release of magnesium ions into the body. ' 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B:

Appl Biomater 89B: 408–414, 2009

Keywords: magnesium; hydroxyapatite; corrosion; biomimetic coating; simulated body fluid

INTRODUCTION

Magnesium can be used as an implant due to its light-

weight and good biocompatibility.1–8 Its mechanical prop-

erties, including fracture toughness, elastic modulus, and

compressive strength, are similar to those of natural bone,

as shown in Table I.9 Magnesium is found in bone tissue

and is an important element for human metabolism.10 It is

the second most abundant intracellular cation.11 Unfortu-

nately, magnesium is a very active metal material. It cor-

rodes rapidly at the physiological pH (�7.4) and

temperature (�378C), which may lead to the loss of me-

chanical integrity before substantial tissue healing

occurs.9,12 Thus, it is crucial to closely control the corro-

sion rate of magnesium in body environment, especially

when it is employed for orthopedic applications.

Protective coatings have also been used to delay the cor-

rosion of Mg. Birbilis et al.13 immersed pure Mg in an

ionic liquid based on bis(trifluoromethanesulfonyl)amide

anions to form a film to slow down the corrosion of mag-

nesium in aqueous chloride-containing solutions, but the

biocompatibility of the film was not tested. If pure magne-

sium is used as an implant in vivo, the protective coating

must be biocompatible. Ideally, the protective layer is bio-

active, which can form osteointegration with the natural

bone. However, due to the extremely high reactivity of Mg,

it is hard to form a coating on magnesium surface in a

chloride-containing solution.14 Hydroxyapatite (HA) has

been used as a coating on Ti and Ti alloys to enhance the

biocompatibility of metallic implants.15 It is the main com-

position of natural bone and tooth. It has excellent bioactiv-

ity and osteoconductivity.16,17 Moreover, it has been

reported that Mg can be incorporated into HA coating, and

the Mg-containing HA coating enhanced bone ingrowth and

improved bone bonding with implants.18 The corrosion resist-

ance of magnesium–HA composites has also been studied.

Witte et al.19 prepared composites made of magnesium alloy

AZ91D and HA particles and found that the addition of HA

particles improved the corrosion resistance of the magnesium

alloy in both artificial sea water and cell medium.

In this work, homogenous single and dual layer biomi-

metic apatite coatings were successfully formed on the sur-

face of magnesium substrate with a purity of 99.9%. Past

attempts in forming bone-like apatite coating on magne-

sium substrates were reported, but apatite was formed

mainly on heat-treated magnesium substrates.1,20,21

Correspondence to: M. Wei (e-mail: [email protected])Contract grant sponsor: Chinese Scholarship CouncilContract grant sponsor: National Science Foundation; Contract grant number:

DMI0500269.

' 2008 Wiley Periodicals, Inc.

408

Li et al.20 treated pure magnesium with a combination of

alkaline soaking and heat treatment. Calcium phosphate was

precipitated on the surface of the treated substrate after

14 days of immersion in SBF. It was believed that the apa-

tite layer formation was attributed to the slow corrosion rate

of the treated substrate. Heat treatment was also employed

by Kuwahara et al.1 and Lopez et al.21 Magnesium apatite

was detected in the former study, whereas bone-like apatite

was formed in the latter study. Both types of apatites con-

tributed to the inhibition of substrate corrosion. However,

the effect of heat treatment on the mechanical properties of

magnesium was not assessed in these reports, which might

be a necessary step to ensure that such a treatment process

do not have a detrimental impact on the material.

In this study, an apatite coating was applied onto the sur-

face of pure Mg using a biomimetic method. The function

of the HA coating was twofold: (1) slow down the degrada-

tion rate of Mg in simulated body fluid and (2) improve the

biocompatibility of magnesium substrates.

EXPERIMENTAL PROCEDURES

Sample Preparation

Pure magnesium (99.9%) ingot was annealed at 5508C for

24 h to obtain homogeneous microstructure and composi-

tion. It was cut into rectangular samples with a size of 25

3 10 3 5 mm3. These samples were ground on 320# wet

SiC paper and ultrasonically cleaned using distilled water

for 5 min at 258C. The samples were then dried using pa-

per towel. The chemical composition of the substrate sur-

face subjected to the three different cleaning steps was

examined using X-ray photoelectron spectroscopy (XPS,

VG Scientific ESCALAB Mark II) with Mg Ka X-ray

source. Samples were mounted on stainless steel stubs

using carbon tape. They were inserted in a prepump cham-

ber, which was evacuated to less than 1 3 1026 torr before

introduction to the analysis chamber. The pressure in the

analysis chamber was maintained at 1028 torr. High-resolu-

tion scans of the O1s, F1s, C1s, and Mg2p regions and full

surveys were carried out for all samples. High-resolution

data was acquired at 0.1 eV/step, and it was deconvoluted

using Casa XPS1

Software in order to obtain an idea of the

bonding states at the surface of these samples. All the spec-

tra were calibrated using the adventitious C1s binding

energy (284.8 eV). Overview spectra were performed in an

energy range of 1100–0 eV at 1 eV/step.

Biomimetic Apatite Coating

In this study, the Mg specimens prepared earlier were

applied with a layer of biomimetic apatite coating using a

concentrated simulated body fluid (3CaP SBF). The 3CaP

SBF solution was prepared based on the procedures

described by Qu et al.22 and Kokubo et al.23 The ion con-

centrations of human blood plasma, 1xSBF, and 3CaP SBF

are listed in Table II. The Ca21 and HPO422 ion concentra-

tions of 3CaP SBF were adjusted to three times as high as

those of the 1xSBF, respectively. Tris-hydroxymethyl ami-

nomethane ((HOCH2)3CNH2) was used as a buffer in the

1xSBF system, whereas 4-(2-hydroxyethyl)-1-piperazinee-

thanesulfonic acid (HEPES) was used in the 3CaP SBF.

The initial pH of both systems was adjusted using hydro-

chloric acid.

Three groups of specimens were studied. Each sample

was immersed in 100 mL 3CaP SBF at 428C for 24 h. The

samples were then removed from the solution, rinsed with

deionized water, and dried in air. Thus treated samples

were named as single apatite coated samples. A group of

the single apatite coated samples was reimmersed in a fresh

3CaP SBF at 428C for 24 h to form a thick apatite coating,

and it was named as dual apatite coated samples. The sam-

ples without any apatite coating were used as controls. Five

samples in each group were examined.

The composition of the coating layer was examined

using both X-ray diffraction (XRD, Bruker AXS D5005 X-

ray) and Amary 1000A energy dispersive X-ray spectros-

copy (EDX). For the XRD examination, a copper target

was used, and the voltage and current setup were 40 kV

and 40 mA, respectively. A step size of 0.028 and a scan

speed of 18/min were used. The morphology of sample sur-

faces was observed by a JEOL JSM 6335F field emission

scanning electron microscope (FESEM).

Corrosion Test

The apatite-coated samples were subsequently soaked in

1xSBF for a degradation test. The 1xSBF was prepared by

dissolving analytical grade reagents such as NaCl,

TABLE II. Ion Concentrations of Human Blood Plasma,1xSBF and 3CaP SBF22,23

Ion

Ion Concentrations

Blood Plasma 1xSBF 3CaP SBF

Na1 142.0 142.0 109.5

K1 5.0 5.0 6.0

Mg21 1.5 1.5 1.5

Ca21 2.5 2.5 7.5

Cl2 103.0 147.8 110.0

HCO32 27.0 4.2 17.5

HPO422 1.0 1.0 3.0

SO422 0.5 0.5 –

Buffer – Tris HEPES

TABLE I. The Physical and Mechanical Properties ofMagnesium in Comparison With Natural Bone9

Properties Natural Bone Magnesium

Density (g/cm3) 1.8–2.1 1.74–2.0

Elastic modulus (GPa) 3–20 41–45

Compressive yield strength (MPa) 130–180 65–100

Fracture toughness (MPam1/2) 3–6 15–40

409CONTROLLING THE BIODEGRADATION RATE OF MAGNESIUM

Journal of Biomedical Materials Research Part B: Applied Biomaterials

NaHCO3, KCl, K2HPO4�3H2O, MgCl2�6H2O, CaCl2, and

Na2SO4 in deionized water. Tris-(hydroxymethyl)aminome-

thane and hydrochloric acid were used to adjust the solu-

tion pH to 7.50 at the temperature of 358C. The samples

without coating were used as controls.

Each sample was immersed in 500 mL SBF at 378C for

24, 72, 168, 360, and 504 h. At each immersion time point,

solution pH and specimen weight were recorded. The cal-

cium concentration in 1xSBF solution was measured using

a Perkin Elmer 3100 atomic absorption spectrometry

(AAS), and the phosphate concentration was measured

using a molybdenum blue method. The results were quanti-

fied using a Biotek MQX200 microplate reader. The sam-

ple surfaces were examined using both FESEM and XRD.

The same settings employed in the last section were also

used here.

RESULTS

Surface Treatment

The surface of the as-cleaned magnesium substrates was

examined using XPS. It was found that the magnesium on

the surface of the sample mainly exists in the following

three forms: pure magnesium, magnesium oxide, and mag-

nesium hydroxide, and they are 33.6%, 7.7%, and 58.6%,

respectively. The as-cleaned surface was also assessed

using EDX, as shown in Figure 1. It was found that the

coating composition is mainly Ca and P, and the intensity

of both Ca and P elements increased as the coating

changed from single layer to dual layers, indicating the

coating thickness increases with coating times. In compari-

son, only magnesium was detected on the surface of the

untreated sample. It was also observed during the experi-

ment that all 3CaP SBF solutions became cloudy after 24 h

of immersion, indicating the precipitation of apatite in the

solution occurred.

Corrosion Test

XRD patterns of the Mg specimen with single and dual

coatings after immersion in SBF for 0, 72, 360, and 504 h

are shown in Figure 2. It was found that both single and

dual layer apatite coatings have been formed on the surface

of pure Mg specimens, and these coatings are poorly crys-

talline (Figure 2A, 0 h and 2B, 0 h). The XRD results also

implied that the dual layer apatite coating is much thicker

than the single layer coating as the relative intensity of the

apatite main peak (328 2h) versus that of Mg (378 2h) is

higher for the former than the latter, which is in good

agreement with the EDX results. When the three types of

samples were immersed in 1xSBF for corrosion test, the in-

tensity of apatite peaks was hardly changed for both single

and dual apatite coated samples between 0 and 360 h of

immersion, suggesting no extra apatite is formed on the

surface of these samples despite of the long soaking time

of 360 h. However, there was a slight decrease of the apa-

tite peak for both single and dual apatite coating samples at

504 h, implying the dissolution of apatite coating might

have occurred. In addition, no apatite was detected on the

surface of any untreated sample during the corrosion test in

1xSBF.

Figure 3 shows the relationship of sample weight loss

versus SBF immersion time. It was observed that the

weight loss of the untreated samples, and the samples

coated with single and dual layers of apatite were 4.38,

2.36, and 0.84%, respectively. The weight loss of the Mg

substrate for samples with single apatite coating was signif-

icantly lower than that of the untreated group, whereas the

samples with dual apatite coatings was the lowest among

the three groups. It was also found that the weight loss of

Figure 1. EDX spectra of samples before immersing in 1xSBF. (A)

untreated, (B) single apatite coated, and (C) dual apatite-coatedsamples.

410 ZHANG, ZHANG, AND WEI


the untreated samples had a very high initial degradation

rate, 0.0633 wt %/h, but it slowed down after the first 24 h

at a rate of 0.0064 wt %/h. The samples with a single coat-

ing layer also exhibited a high degradation rate initially,

0.0217 wt %/h. After the first 24 h, however, the degrada-

tion rate reduced to 0.0038 wt %/h. In contrast, the samples

with dual coatings demonstrated a very slow degradation

rate of the substrate. The degradation rate was low and

steady throughout the entire 504 h of the test.

Characterizations

Figure 4 shows the pH change of the SBF solution versus

the sample immersion time. The pH of all three SBF solu-

tions increased with the immersion time. At the first 24 h,

a sharp pH increase from 7.5 to nearly 7.8 was observed

for all three groups of samples. After 504 h, the pH change

of the three solutions slowed down. It reached 8.38, 8.29,

and 8.03 at the end of the test for untreated, single layer

coated, and dual layer coated samples, respectively. Obvi-

ously, the pH change for the untreated group was the high-

est, 0.98 pH units, among the three groups within the

testing period. The pH change of the solution immersed

with samples of single apatite coated samples was slightly

lower than that of the untreated sample, 0.89 pH units. In

comparison, the pH change in the solution immersed with

samples of dual apatite coating was the lowest, 0.63 pH

units, during the 504 h of testing time.

The surface morphology of samples after immersing in

1xSBF for 0, 72, 360, and 504 h was observed using

ESEM (Figure 5). For the untreated sample, a mud-crack-

like layer was formed on the surface of the sample. The

width of the cracks increased with the immersion time in

SBF, but the number of cracks decreased (Figure 5 A1–4).

No apatite deposition was observed during the 504 h of

corrosion test in 1xSBF. For the coated samples, homoge-

nous, well adhere single and dual apatite coatings were

formed in 3CaP SBF (Figure 5 B1 and C1). Many small

spherical apatite clusters with an average size of 17.7 lmwere observed on the surface of the single layer coated

Figure 2. XRD patterns of samples with single apatite coating and

dual apatite coatings after immersing in 1xSBF (A) single apatitecoating samples and (B) dual apatite coating samples.

Figure 3. Weight loss of samples after immersing in 1xSBF. (A)

untreated, (B) single apatite coated, and (C) dual apatite-coated

samples.

Figure 4. The pH change in 1xSBF solution after immersed with (A)untreated sample, (B) single apatite coating, and (C) dual apatite

coating.



samples before soaking in 1xSBF (Figure 5 B1). These par-

ticles were not densely packed, and many pores were pres-

ent among apatite clusters. The surface morphology of the

coating hardly altered with the soaking time (Figure 5 B2–

4). Similar to single layer coated specimens, spherical apa-

tite clusters were also observed on the surface of the dual

coating specimens, but these clusters (�8.0 lm in diame-

ter) were much smaller than those formed directly onto the

surface of Mg metals (Figure 5 C1). Pores were also

observed among these tiny apatite clusters. After immersing

the dual-coated samples in 1xSBF, spherical apatite clusters

were also formed (Figure 5 C2–4). Interestingly, the size of

these spherical clusters increased substantially with the

soaking time. An average apatite cluster diameter of 8.0,

24.1, 40.9, and 49.0 lm were observed for samples soaked

in 1xSBF for 0, 72, 360, and 504 h, respectively. The large

clusters formed at the later stage of the soaking (360 and

504 h) were better packed and had less pores among them.

Figure 6 shows the change of calcium and phosphate

concentrations in 1xSBF with soaking time. It was discov-

ered that the phosphate concentration in 1xSBF maintained

relatively stable with the extension of the immersion time

for all three groups of samples. In contrast, the calcium

concentration in the solution fluctuated with immersing

Figure 5. Surface morphologies of (A) untreated, (B) single apatite coated, and (C) dual apatite-coated samples immersed in 1xSBF for (1) 0, (2) 72, (3) 360, and (4) 504 h.

Figure 6. Calcium and phosphate concentration changes in 1xSBF soaked with (A) untreated, (B)

single apatite coated, and (C) dual apatite-coated samples.



time for all three groups of samples. Nevertheless, the

calcium concentration for both untreated and dual-coated

samples maintained relatively stable during the entire soak-

ing period, whereas that for the single-coated samples

decreased with immersion time. Such decrease was stabi-

lized between 360 and 504 h.

DISCUSSION

In this study, bone-like apatite was formed on the surface

of a 99.9% magnesium substrate without any preheat treat-

ment. The formation of apatite in our study was mainly

due to the employment of 3CaP SBF whose calcium and

phosphate ion concentrations were three times as high as

those of 1xSBF. In addition, the surface cleaning process

may be beneficial to the apatite formation, which has been

discussed in the later section. At the initial stage of immer-

sion in 3CaP SBF, two counteracting processes occurred in

the solution. On one hand, apatite nucleated and grew on

the surface of magnesium, see Reaction (1). After ultra-

sonic washing, our XPS results revealed that a layer mainly

composed of Mg(OH)2 was formed on the surface of the

substrate, which might have contributed to the apatite

nucleation and growth by providing OH2 groups. On the

other hand, magnesium was corroded in 3CaP SBF result-

ing in the release of magnesium ions as well as hydrogen

gas bubbles as illustrated in Reaction (2). Large amount of

gas bubbles emitted from the substrate would prevent apa-

tite coating from forming on the surface of the metal sub-

strate. Apparently, the corrosion rate of our substrate was

retarded due to the formation of a Mg(OH)2 layer on the

surface of pure magnesium, and thereby enabled the depo-

sition of apatite on the as-cleaned substrate surface.

5Ca2þ þ 3HPO2�4 þ 4OH� ! Ca5ðPO4Þ3OHþ H2O ð1Þ

Mgþ 2H2O ! Mg2þ þ 2ðOH�Þ þ H2 " ð2Þ

Besides the control group (without surface treatment),

two testing groups were studied, single and dual apatite

coated samples. After soaking the samples in 3CaP SBF

for 24 h, most of the calcium and phosphate ions in the so-

lution were used up due to their participation in the forma-

tion of the apatite coating on the magnesium substrate as

well as the precipitates in the solution. As a result, the

coating could no longer be formed after 24 h of immersion

in 3CaP SBF. Thus, it is necessary to produce dual coat-

ings instead of simply extending the coating time to

achieve a thick apatite coating.

One can also conclude from Reaction (2) that the degra-

dation of Mg is accompanied by the pH increase in the so-

lution. This was well manifested in our study (Figure 4).

Because of the presence of chloride in 1xSBF solution, the

initial degradation rate of the samples was fast for all three

groups. A sharp increase of pH in the first 24 h of soaking

was observed. After the first 24 h, a thick Mg(OH)2film was formed (Figure 5 A2–4), and the degradation rate

of all three groups of samples slowed down (Figure 3).

Similar to the change of degradation rates, the pH increase

in 1xSBF soaked with different samples also illustrated

the same trend: untreated [ single coat [ dual coats

(Figure 4).

The weight change of the samples in 1xSBF was a result

of the following three processes: (1) the degradation of

magnesium, (2) the precipitation of apatite coating, and (3)

the dissolution of apatite coating. The degradation of mag-

nesium occurred for all three groups of samples, but their

degradation rates were significantly different owing to var-

ied surface treatments applied to the substrate, including no

coating, single apatite coating and dual-apatite coating.

Besides the degradation of magnesium, apatite precipitation

and dissolution were two processes continuously occurred

during the 1xSBF soaking. As the apatite coating formed

was poorly crystalline (Figure 2), it could dissolve in a

physiological solution at a body temperature.24 We propose

that the apatite coating underwent a dynamic process of

precipitation and dissolution during the entire 1xSBF soak-

ing. For the samples with a single apatite coating, more ap-

atite coating was formed during the soaking in 1xSBF,

where the apatite precipitation process predominated over

the dissolution process. This was supported by our ion con-

centration test where a slight decrease of both calcium and

phosphate ion concentrations during the soaking period was

observed (Figure 6). However, the calcium and phosphate

ion concentration in the 1xSBF soaked with either

untreated or dual apatite coated samples remained almost

unchanged during the soaking period. There are two factors

that may contribute to the apatite formation on the single

layer apatite coated samples. First, the primary layer of ap-

atite coating provided nucleation sites for further apatite

deposition. Second, the pH of the 1xSBF solution became

high with the soaking time, which provided the necessary

OH2 groups for apatite formation. In contrast, the

untreated samples did not have the primary apatite coating

acting as the nucleation sites, although the pH in the solu-

tion was high. As a result, no apatite was formed even after

more than 500 h of soaking in 1xSBF. Although the dual

apatite coated samples had the apatite coating to provide

nucleation sites, the pH in the solution was not high

enough to induce apatite coating formation. Nevertheless,

the dual apatite coating went through a constantly dissolv-

ing and reprecipitation process, resulting in the change of

apatite cluster size with the soaking time (Figure 5). Obvi-

ously, applying both single and dual apatite coatings onto

the surface of the magnesium substrate has significantly

retarded the corrosion rate of pure magnesium. Further-

more, the dual apatite coating (0.84% weight loss after 504

h of immersion in 1xSBF) was more effective than the

single coating (2.36% weight loss after 504 h of immersion

in 1xSBF) in hindering the corrosion of the substrate

(Figure 3).



CONCLUSIONS

In summary, a homogenous bone-like apatite coating was

successfully formed on the surface of 99.9% pure magne-

sium using a biomimetic coating method. No heat treatment

was required to apply to the magnesium substrate. The apa-

tite coatings greatly retarded the corrosion rate of the mag-

nesium substrate. It was also concluded that a dual apatite

coating was more effective in slowing down the corrosion

rate of the substrate than the single apatite coating. Thus,

the degradation rate of magnesium and its alloys can be tai-

lored by closely controlling the apatite coating thickness.

Such prepared apatite-coated magnesium implants will not

only have the controlled degradation rate but also have

excellent bioactivity suitable for different biomedical appli-

cations.

The authors would like to thank Dr. Daniel Goberman forhis assistance with XPS study, Dr. Abhay Vaze and Mr. XiaohuaYu for their assistance with Ca and P concentration measure-ments, and Dr. Yong Wang for providing Mg samples. Financialsupports from both the Chinese Scholarship Council (YajingZhang) and National Science Foundation (Mei Wei) were grate-fully acknowledged.

REFERENCES

1. Kuwahara H, Al-Abdullat Y, Ohta M, Tsutsumi S, Ikeuchi K,Mazaki N, Aizawa T. Surface reaction of magnesium inHank’s solutions. Mater Sci Forum 2000;350:349–358.

2. Schranz D, Zartner P, Michel-Behnke I, Akinturk H. Bioab-sorbable metal stents for percutaneous treatment of criticalrecoarctation of the aorta in a newborn. Cathet CardiovascIntervent 2006;67:671–673.

3. Zartner P, Cesnjevar R, Singer H, Weyand M. First successfulimplantation of a biodegradable metal stent into the left pul-monary artery of a preterm baby. Cathet Cardiovasc Intervent2005;66:590–594.

4. Witte F, Kaese V, Haferkamp H, Switzer E, Meyer-Linden-berg A, Wirth CJ, Windhagen H. In vivo corrosion of fourmagnesium alloys and the associated bone response. Biomate-rials 2005;26:3557–3563.

5. Mueller D, Nascimento ML, Zeddies M, Corsico M, GassaLM, Fernandez MA, de Mele L. Magnesium and its alloys asdegradable biomaterials. Corrosion studies using potentiody-namic and EIS electrochemical techniques. Mater Res 2007;10:5–10.

6. Qiao L, Gao J, Wang Y, Wang S, Wu S, Xue Y. Biocompati-bility evaluation of magnesium-based materials. Mater SciForum 2007;546–549:459–462.

7. Duygulu O, Kaya RA, Oktay G, Kaya AA. Investigation onthe potential of magnesium alloy AZ31 as a bone implant.Mater Sci Forum 2007;546–549,421–424.

8. Hermawan H, Moravej M, Dube D, Fiset M, Mantovani D.Degradation behavior of metallic biomaterials for degradablestents. Adv Mater Res 2007;15–17:113–118.

9. Staiger MP, Pietak AM, Huadmai J, Dias G. Magnesium andits alloys as orthopedic biomaterials: A review. Biomaterials2006;27:1728–1734.

10. Okuma T. Magnesium and bone strength. Nutrition 2001;17:679–680.

11. Feillet-Coudray C, Coudray C, Wolf FI, Henrotte JG, Rayssi-guier Y, Mazur A. Magnesium metabolism in mice selectedfor high and low erythrocyte magnesium levels. Metab ClinExp 2004;53:660–665.

12. Saris NEL, Mervaala E, Karppanen H, Khawaja JA, Lewen-stam A. Magnesium—An update on physiological, clinicaland analytical aspects. Clin Chim Acta 2000;294:1–26.

13. Birbilis N, Howlett PC, MacFarlane DR, Forsyth M. Explor-ing corrosion protection of Mg via ionic liquid pretreatment.Surf Coat Technol 2007;201:4496–4504.

14. Gray JE, Luan B. Protective coatings on magnesium and itsalloys—A critical review. J Alloys Compd 2002;336:88–113.

15. Habibovic P, Barrere F, Blitterswijk CA, de Groot K, Layr-olle P. Biomimetic hydroxyapatite coating on metal implants.J Am Ceram Soc 2002;85:517–522.

16. Hench LL. Bioceram J Am Ceram Soc 1998:81:1705–1728.17. Park JB, Lakes RS. Biomaterials: An Introduction. New

York: Plenum Press; 1992. p 185–222.18. Revell PA, Damien E, Zhang XS, Evans P, Howlett CR. The effect

of magnesium ions on bone bonding to hydroxyapatite coating ontitanium alloy implants. Key EngMater 2004; 254:447–450.

19. Witte F, Feyerabend F, Majer P, Fischer J, Stormer M, Bla-wert C, Dietzel W, Hort N. Biodegradable magnesium-hy-droxyapatite metal matrix composites. Biomaterials 2007;28:2163–2174.

20. Li L, Gao J, Wang Y. Evaluation of cytotoxicity and corro-sion behavior of alkali-heat-treated magnesium in simulatedbody fluid. Surf Coat Technol 2004;185:92–98.

21. Lopez HY, Cortes DA, Escobedo S, Mantovani D. In vitrobioactivity assessment of metallic magnesium. Key Eng Mater2006;309–311:453–456.

22. Qu H, Wei M. Improvement of adhesive strength of biomi-metically coated titanium implants. J Biomed Mater Res2008;84:436–443.

23. Kokubo T, Takadama H. How useful is SBF in predictingin vivo bone bioactivity? Biomaterials 2006;27:2907–2915.

24. Iezzi G, Scarano A, Petrone G, Piattelli A. Two human hy-droxyapatite-coated dental implants retrieved after a 14-yearloading period: A histologic and histomorphometric casereport. J Periodontol 2007;78:940–947.



controlling the biodegradation rate of magnesium using biomimetic apatite coating

Documents