Clinical Device-Related ArticleOptimal Sterilization Method for the Zirconia/Alumina CompositesUsed for Total Hip Replacements

Kwang Woo Nam,1,2 Jeong Joon Yoo,3 Kyung-Hoi Koo,4 Kang Sup Yoon,5 Hee Joong Kim3,6

1 Department of Orthopaedic Surgery, Cheju National University Hospital, Jeju, 690-716, Korea

2 Institute of Medical Science, Cheju National University, Jeju, 690-756, Korea

3 Department of Orthopaedic Surgery, Seoul National University Hospital, Seoul, 110-744, Korea

4 Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, 463-707, Korea

5 Department of Orthopaedic Surgery, Seoul Municipal Boramae Hospital, Seoul, 156-707, Korea

6 Medical Research Center, Seoul National University, Seoul, 110-744, Korea

Received 18 June 2008; revised 17 December 2008; accepted 14 January 2009Published online 13 May 2009 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.b.31358

Abstract: Zirconia/alumina composite ceramics have been recently developed for total hiparthroplasty because of their excellent mechanical properties and tribologic characteristics.All such materials used clinically must be easily sterilized, but no report has been issuedconcerning methods for sterilizing zirconia/alumina composite hip prostheses. Here, we showthat 50 kGy of gamma irradiation effectively sterilizes both the surfaces and interiors of thesematerials. In addition, it was found that the commonly used ethylene oxide and 25-kGy gammairradiation sterilization methods inadequately sterilize deep inside the femoral head.Moreover, no changes in the chemical or mechanical properties of the composites were notedafter exposure to 50-kGy gamma irradiation. We suggest that 50-kGy gamma irradiation is anoptimal sterilization method for zirconia/alumina composite total hip replacements. ' 2009

Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 90B: 962–966, 2009

Keywords: zirconia; alumina; sterilization; composite; hip prosthesis

INTRODUCTION

Infection after total hip replacement is the most serious

problem which requires much time and incurs substantial

costs.1,2 To prevent surgical infection, several sterilization

methods, such as, steam or dry-heat, ethylene oxide gas,

and gamma irradiation are currently used.

Zirconia and alumina ceramics are commonly used in total

hip arthroplasty because of their superior mechanical proper-

ties and tribologic performances as compared with metal or

polyethylene.3–6 However, little information is available con-

cerning their sterilization capabilities.7 Furthermore, no report

has been issued on the effectiveness of different sterilization

methods for zirconia/alumina composite hip prostheses.

It is known that steam and dry-heat sterilization methods

should be avoided because yttria-stabilized zirconia

degrades at comparatively low temperatures and therefore,

ethylene oxide and gamma irradiation have been used to

sterilize these composites.8–11

The objective of this study was to evaluate the steriliza-

tion effectiveness of ethylene oxide gas and gamma irradia-

tion for zirconia/alumina composite hip prostheses, and to

determine their effects on the chemical and mechanical

properties of the composites. In addition, we undertook to

define an optimal method for sterilizing zirconia/alumina

composites used for total hip replacement.

MATERIALS AND METHODS

Sample preparation

All samples were prepared at the Research and Develop-

ment Center of The Environmental Process and Material

Correspondence to: J. J. Yoo (e-mail: jjyos@snu.ac.kr)Contract grant sponsor: Cheju National University Hospital Cancer Research

Fund; contract grant number: #2007Contract grant sponsor: Grant in Aid for Strategy Technology Development Program of

the KoreanMinistry of Knowledge Economy; contract grant number: #10030019-2007-11

' 2009 Wiley Periodicals, Inc.

962

(C.M.KOR Co., Puchon, Korea). Two types of zirconia/alu-

mina composites, i.e., Z/A#1: ((3.0Y, 1.6Nb, 4.0Ce)-TZP/

20vol% Al2O3) and Z/A#2: ((3.0Y, 1.6Nb, 4.0Ce)-TZP/

80vol% Al2O3) were prepared for the experiment. Compos-

ite compositions were die-pressed into a spherical femoral

head shape (diameter 28 mm) with an internal recess, and

then isostatically pressed at 140 MPa. The green compacts

so produced were then sintered in air for 2 h at 15508C,and the sintered spherical heads obtained were ground and

polished to a surface roughness of Ra\ 0.03 lm.

A total of 70 femoral head samples (Z/A#1; 35 samples,

Z/A#2; 35 samples) were prepared for analysis. Samples

were allocated to three study groups according to the steri-

lization method used, that is, ethylene oxide gas, gamma

irradiation at 25 kGy, and gamma irradiation at 50 kGy (10

Z/A#1 and 10 Z/A#2 were allocated to each group). Five

nonsterilized Z/A#1 and five nonsterilized Z/A#2 samples

were used as controls (Table I). In addition, identical num-

bers of pellet-shaped samples were prepared for chemical

and mechanical tests.

Intentional Contamination

All of the femoral head samples were intentionally conta-

minated with common pathogenic bacteria, that is, coagu-

lase negative Staphylococcus (CNS) and Escherichia coli(E. coli) to estimate the effects of the three sterilization

methods. Briefly, nutrient broths that had been inoculated

with both CNS and E. coli were incubated in flasks at

378C in a humid 5% CO2 atmosphere for 72 h. Femoral

head samples were then soaked in these nutrient broths for

7 days and then dried in air for 48 h before sterilization.

Sterilization Procedure

In the case of ethylene oxide gas sterilization, samples

were exposed to ethylene oxide at a concentration of

900 mg/L for 3 h at 558C in an ethylene oxide sterilizer

(HS-700EO, Hanshin, Seoul, Korea). Gamma irradiation

sterilization was performed using a 60Co irradiator at the

Radiation Application Research Division of the Korea

Atomic Energy Research Institute (KAERI, Jeongeup,

Korea). Samples were packed in plastic bags and exposed

to gamma irradiation at 25 or 50 kGy in air at 228C. Con-trol samples were not sterilized after being contaminated.

Bacteriological Study

Two separate bacteriological studies were performed to

determine the effectiveness of the sterilization procedures.

First, a surface culture was conducted by swabbing the sur-

face and the inner recess of the femoral head samples. The

samples were then broken into pieces using a mechanical

compressor in a sterile environment. Briefly, samples were

wrapped several times in autoclave sterilized linen, and

then fragmented using the mechanical compressor. The

fragments obtained were then immediately placed in flasks

containing nutrient broth. All procedures were performed

on a clean bench. Deep culture was performed by soaking

the fragments in nutrient broth for 48 h. The specimens

were then inoculated on blood agar and MacConkey agar

plates and incubated at 378C in a humid 5% CO2 atmos-

phere for 7 days. Bacterial identifications were performed

using microorganism detection kits (RapIDTM System,

Remel, Lenexa, USA) when bacterial growth was observed.

Chemical and Mechanical Tests

Chemical and mechanical tests were conducted on the sam-

ple pellets described above (35 Z/A#1 and 35 Z/A#2 pel-

lets). Possible compositional changes in zirconia/alumina

composites caused by sterilization were investigated using

an X-ray diffraction unit (XRD; PW3719, Philips, USA),

and changes in mechanical strengths were determined using

a flat-on-three ball biaxial flexural strength with the hard-

ness tester (MMT-3, Matsuzawa, Japan). Inter-group differ-

ences in mean biaxial flexural strengths were analyzed by

one-way ANOVA. p values of \0.05 were considered sig-

nificant.

RESULTS

Swabs of all 10 samples in the nonsterilized control group

regardless of composite type, produced large amounts of

bacterial growth on blood agar and on MacConkey agar

plates. Bacterial identification revealed both CNS and

E. coli in all samples. Conversely, all 60 femoral heads in

the study groups showed no bacterial growth at 2 weeks af-

ter inoculation.

When fragments were cultured, all 10 control group

samples produced large amounts of CNS and E. coli. Bac-terial growth was observed, however, in the 12 samples (8

of 10 Z/A#1 and 4 of 10 Z/A#2 samples) in the ethylene

oxide group and in 8 samples (4 of 10 Z/A#1 and 4 of 10

Z/A#2 samples) in the 25-kGy gamma irradiation group. A

substantial amount of Bacillus was identified in all above

20 samples, but CNS and E. coli were not detected (Table

II). In contrast, no bacterial growth was observed for any

of the 50-kGy gamma radiation treated 20 samples.

Seventy sample pellets (35 Z/A#1 and 35 Z/A#2 pellets)

were tested for X-ray diffraction analysis with special refer-

ence to changes of phases of zirconia (from tetragonal to

monoclinic zirconia). No compositional changes were

TABLE I. Numbers of Specimens and Study Groupsa

Group

Z/A#1 ((3.0Y,

1.6Nb, 4.0Ce)-

TZP/20vol%

Al2O3)

Z/A#2 ((3.0Y,

1.6Nb, 4.0Ce)-

TZP/80vol%

Al2O3)

Ethylene oxide gas 10 10

25 kGy gamma radiation 10 10

50 kGy gamma radiation 10 10

Control (nonsterilized) 5 5

a Identical numbers of pellet shaped samples were prepared for chemical and me-

chanical tests.

963OPTIMAL STERILIZATION METHOD FOR THE ZIRCONIA/ALUMINA COMPOSITES

Journal of Biomedical Materials Research Part B: Applied Biomaterials

observed by chemical testing. No evidence of zirconia

phase transformation was observed in any sample after any

sterilization treatment (Figure 1).

The mechanical strengths of the composites of 70 sam-

ple pellets as determined by biaxial flexural strength are

shown in Table III. No significant change in mechanical

strength was observed in any group (p 5 0.93 for Z/A#1

and p 5 0.52 for Z/A#2).

DISCUSSION

Alumina and zirconia possess excellent tribologic resistance

and have been used to reduce prosthetic wear caused by

articulating surface contact.3–6,12–14 However, alumina has

a risk of catastrophic failure because of fracture and yttria-

stabilized zirconia degrades at comparatively low tempera-

tures despites high fracture toughness.8–11,15 Recently, zir-

conia/alumina composites have been developed to make up

for these weak points.16 Although all materials must

be sterilized before clinical use, no report has yet been

issued on the sterilization of zirconia/alumina composite

hip prostheses.

A number of methods can be used to sterilize zirconia/

alumina composites, for example, chemical detergents,

steam or dry-heat sterilization, ethylene oxide gas, and

gamma irradiation. However, steam and dry-heat steriliza-

tion methods have been found to cause a phase change and

surface roughening of yttria-stabilized zirconia femoral

head components.8,9,11,15 Furthermore, this phase change

increases wear and can cause premature component failure.

Therefore, sterilization by ethylene oxide and gamma irra-

diation, particularly at 25 kGy, is widely used to sterilize

medical devices and supplies containing polyethylene, zir-

conia, or alumina ceramic components.

Our experiments showed that 50-kGy gamma irradiation

effectively sterilized the surfaces and the interiors of zirco-

nia/alumina composite femoral heads, whereas ethylene ox-

ide gas and 25-kGy gamma irradiation only sterilized

surfaces. The bacteria identified within ceramics sterilized

using ethylene oxide or 25-kGy gamma irradiation were all

Bacillus species. To avoid the possibility of culture con-

tamination during the experiment, great care was taken to

avoid possible contamination when fragmenting specimens,

and to properly sterilize the linen used. Furthermore, all

positive fractured samples after sterilization showed bacil-

lus and none of the control group samples was contami-

nated with any bacillus other than CNS and E. coli, whichexcludes the possibility of contamination. Moreover, no ba-

TABLE II. Positive Rates for the Culture of FracturedSpecimens

Group Z/A#1 Z/A#2

Ethylene oxide gas 80% (8 of 10)a 40% (4 of 10)a

25 kGy gamma radiation 40% (4 of 10)a 40% (4 of 10)a

50 kGy gamma radiation 0% 0%

Control (nonsterilized) 100% (5 of 5)b 100% (5 of 5)b

a Bacillus species were identified.b Coagulase negative Staphylococcus and Escherichia coli were identified.

Figure 1. X-ray diffraction analysis findings of specimens: No phase transformation of zirconia

(from tetragonal ZrO2 to monoclinic ZrO2) was observed in any of the three study group (ethylene ox-

ide, 25 kGy, and 50 kGy gamma radiation groups). (A) Z/A#1 compositions after sterilization. (B) Z/A#2

compositions after sterilization. ! tetragonal ZrO2 ! monoclinic ZrO2 n Al2O3.

964 NAM ET AL.

Journal of Biomedical Materials Research Part B: Applied Biomaterials

cillus was identified in fractured specimens in the 50 kGy

group, and no bacteria were grown from the linen used to

wrap specimens.

Bacterial spores of the bacillus strain are extremely re-

sistance to pressure and temperature,17–22 for example they

can survive a pressure of 1000 MPa and a temperature of

6008C in the dehydrated state.23,24 Hence, it is likely that

they survive composite manufacturing processes, and thus

the bacillus contamination found in the ethylene oxide-and

25 kGy-sterilized groups likely occurred when the speci-

mens were manufactured.

The spores of bacillus genus are found ubiquitously in

the environment and its presence is usually ignored due to

its nonpathogenic nature. However, the incidences of seri-

ous infections caused by bacillus, such as, osteomyelitis

and septic arthritis, have increased over the past three deca-

des, especially in patients with artificial prostheses.25,26

Although zirconia/alumina composites have excellent

wear resistance, the inner portions of these composites can

be exposed to forces that cause excessive wear or break-

age.27–30 If this occurs, released dormant bacterial spores

can germinate and proliferate to cause infection, which is

the most disastrous complication of total hip arthroplasty.

The results of the present study show that the steriliza-

tion efficacy of 50-kGy gamma irradiation is greater than

that of the other sterilization methods examined. Moreover,

this sterilization treatment had no observable detrimental

effect upon the chemical or mechanical properties of the

zirconia/alumina composites.

CONCLUSION

Gamma radiation at 50 kGy was found to optimally steri-

lize zirconia/alumina total hip replacement composites

without adversely affecting their chemical or mechanical

properties.

The authors thank Hyung Bong Lim (R&D Center, C.M.KORCo., Puchon, Korea) for preparing samples and Dae Jong Han(Microbiology Laboratory, Clinical Research Institute, SeoulNational University Hospital, Seoul, Korea) for assistance withthe microbiological study.

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TABLE III. Biaxial Flexural Strength Findings of Specimensa

Group Z/A#1 (MPa) Z/A#2 (MPa)

Ethylene oxide gas 694.7 6 49.8 753.3 6 28.9

25 kGy gamma radiation 692.0 6 15.9 739.0 6 48.4

50 kGy gamma radiation 690.7 6 19.1 767.0 6 16.2

Control (nonsterilized) 693.8 6 42.6 745.8 6 34.7

a Values represent the mean and standard deviation.

965OPTIMAL STERILIZATION METHOD FOR THE ZIRCONIA/ALUMINA COMPOSITES

Journal of Biomedical Materials Research Part B: Applied Biomaterials

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