Effect of Ionizing Irradiation on Mechanical Properties and Translucency of Monolithic Zirconia

by:

Abdullah Alshamrani

A thesis submitted in conformity with the requirements for the degree of Master of Science

Graduate Department of Dentistry

University of Toronto

© Copyright by Abdullah Alshamrani, 2019

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Effect of Ionizing Irradiation on Mechanical Properties and Translucency of Monolithic Zirconia

Abdullah Alshamrani

Master of Science

Faculty of Dentistry

University of Toronto

2019

ABSTRACT

Objectives: To evaluate the effect ionizing irradiation therapy (RT) on mechanical properties and

translucency of monolithic zirconia.

Methods: High translucency (HT) and low translucency (LT) yttria-stabilized zirconia (Y-PSZ)

were used to prepare 60 bar-shaped fully sintered specimens (14×4×1.5mm) of each material and

allocated in four groups (n=30): Control or irradiated (70 Grays single dose). Specimens were

evaluated for flexural strength (FS) (n=10), fatigue limits (FLs) at 100,000 cycles (n=15), and

translucency parameter (TP)(n=5). Data of FS and TP were analyzed by one-way Analysis of

Variance (ANOVA) and Tukey HSD. FLs data was analyzed using Dixon and Mood method.

Results: RT affected FS (p<0.05) of LT specimens, but not the FS of HT (p=0.86). TP value and

FLs of both materials were not affected by RT (p>0.05).

Conclusion: RT has a negative effect on flexural strength of LT Y-PSZ, but not on fatigue limits

and translucency of LT and HT Y-PSZ.

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ACKNOWLEDGEMENTS

I am grateful to the many individuals who contributed to my education, culminating in

achieving this master’s degree.

Firstly, I would like to sincerely thank my supervisors: Dr. Grace De Souza for her

invaluable advice and guidance throughout the project. I would like to express my gratitude for

her help whenever I had a problem with my experiments. I am very grateful for the time that she

dedicated to this project. Without her support and help, this project would never have been

completed.

I would like to express my sincere thankfulness to my committee members, Dr. Anil

Kishen and Dr. Eli Sone for their invaluable advice over the period of my research project. They

provided helpful assistance and advice for this work.

I am very grateful to my friends and collogues for their support, encouragement, and

valuable suggestions throughout the graduate program.

I would like to thank the school of graduate studies (SGS), University of Toronto, for

providing me the chance to complete my master’s degree and providing a helpful environment.

I would also express my gratitude to King Saud University, and Saudi Arabian Culture

Bureau (SACB) who provided me with the scholarship, and financial support for this project. I

could not have come here for studying without their support.

Finally, I would like to take this opportunity to thank my beautiful wife for her

unconditional love and support throughout my life. Thank you for giving me the strength and

encouraging me to believe in myself and to reach my goals. To my beloved family, thank you for

your endless love and encouragement.

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TABLE OF CONTENTS

LIST OF TABLES…………………………………………………..………………………………….……..………...…..vi

LIST OF FIGURES …………………………………………………………………………………………………….……vii

LIST OF ABBREVIATIONS ………………………………………………………..…..…………………………….viii

I. GENERAL INTRODUCTION AND LITERATURE REVIEW ..................................... 1

1. Dental ceramics ..................................................................................................................... 3

1.1 History of dental ceramics .............................................................................................. 3

1.2 Classification of all-ceramic systems ............................................................................. 5

1.2.1 Predominantly glassy materials .............................................................................. 5

1.2.2 Particle-filled glasses ................................................................................................ 5

1.2.3 Polycrystalline ceramics .......................................................................................... 6

2. Monolithic zirconia ............................................................................................................... 6

2.1 Structure and compositions of monolithic zirconia ..................................................... 6

2.2 General properties of zirconia ....................................................................................... 7

2.2.1 Transformation toughening .................................................................................... 7

2.2.2 Low-temperature degradation ................................................................................ 8

2.3 Main applications of zirconia in dentistry .................................................................... 8

2.4 Different generations of monolithic zirconia in dentistry ........................................... 9

2.4.1 First generation of zirconia (3Y-TZP) ................................................................... 9

2.4.2 Second generation of zirconia (monolithic 3Y-TZP) .......................................... 10

2.4.3 Third generation of zirconia (5Y-PSZ) ................................................................ 10

3. Characteristics of monolithic zirconia .............................................................................. 11

3.1 Flexural strength ........................................................................................................... 11

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3.2 Fatigue behavior ............................................................................................................ 13

3.3 Optical properties ......................................................................................................... 16

4. Radiation therapy (RT) ..................................................................................................... 19

4.1 Principles of radiation therapy .................................................................................... 19

4.2 Oral complication following radiation therapy .......................................................... 19

4.4 Possible interaction between ionizing radiation and zirconia ................................... 21

II. RATIONALE, OBJECTIVES & HYPOTHESES ....................................................... 22

1-Rationale ............................................................................................................................... 22

2- Objectives ............................................................................................................................ 23

3- Null (H0) hypotheses .......................................................................................................... 23

III. MANUSCRIPT ..................................................................................................................... 24

IV. DISCUSSION ........................................................................................................................ 51

V. CONCLUSION ...................................................................................................................... 57

VI. FUTURE DIRECTIONS ..................................................................................................... 58

VII. REFERENCES .................................................................................................................... 59

VI. APPENDICES ...................................................................................................................... 82

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LIST OF TABLES

Table I. Description of the zirconia-based materials used in the current study

29

Table II.

Mean values of flexural strength, initial fatigue limit, step size, fatigue limit data (in MPa) after 100,000 cycles and decrease from flexural strength to fatigue limit (%).

33

Table III. Summary of survival behavior of tested materials, and the probability of survival (%) for each group.

36

Table IV. Mean (SD) translucency parameter values for the tested material.

37

Table V.

Comparative mean of grain size (µm), and standard deviation (SD) of zirconia materials used in the study.

38

Table VI. Crystalline phase composition of Y-PSZ materials used in this study.

40

vii

LIST OF FIGURES

Figure 1.

Assembly for both, three-point-bending and fatigue test

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Figure 2. Bar graph illustrating the flexural strength results (in MPa) of the tested materials. Data are presented as mean ± standard deviation. Different lowercase letters indicate significant differences at 5% significance level

32

Figure 3. Staircase for LT-C. The red line indicates the mean fatigue limit (404.99 MPa), the black shaded elements indicate the surviving specimens, the white indicate failed specimens

33

Figure 4. Staircase for LT-I. The red line indicates the mean fatigue limit (464.31MPa), the black shaded elements indicate the surviving specimens, the white indicate failed specimens

34

Figure 5. Staircase for HT-RT. The red line indicates the mean fatigue limit (183.01MPa), the black shaded elements indicate the surviving specimens, the white indicate failed specimens

34

Figure 6. Staircase for HT-I. The red line indicates the mean fatigue limit (197.25MPa), the black shaded elements indicate the surviving specimens, the white indicate failed specimens

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Figure 7. Survival graphs obtained by Kaplan-Meier and Log-rank tests for number of cycles for failure (MPa). It indicates the fatigue behavior of each group: LT-C (blue line), LT-RT (green line), HT-C (yellow line), and HT-RT (purple line)

36

Figure 8.

Quantitative results of chemical composition of tested materials. a) LT- 3Y-PSZ (IPS e.max Zircad); b) HT- 5Y-PSZ (Ceramill Zolid FX)

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Figure 9. SEM images (original magnification ×10,000) of the bar-shaped samples indicating different crystalline structures of zirconia materials with different levels of translucency: a) Low Translucency – Control; b) Low Translucency – Irradiated; c) High Translucency- Control; d) High Translucency - Irradiated. Similar crystalline composition was observed between a and b samples; c and d samples show large cubic grains

39

viii

LIST OF ABBREVIATIONS

RT Radiation Treatment HNC Head and neck cancer XRD X-ray diffraction analysis EDS Energy dispersive X-ray spectrometer SEM Scanning electron microscope LTD Low thermal degradation CTE Coefficient thermal expansion

CAD/CAM Computer Assisted Design/Computer Assisted Machining, which is a technology used to fabricate restoration by machining it from a ceramic block

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I. GENERAL INTRODUCTION AND LITERATURE REVIEW

Metal-ceramic restorations were considered the standard treatment for fixed dental prostheses

for more than 40 years, but the esthetic demand towards all-ceramic restorations has increased

over the last two decades. This is due to the superior esthetics when the metal is absent, and also

because all-ceramic restorations do not cause allergies as the metal alloys do (Li et al., 2014;

Studart et al., 2007b). Many ceramic materials have been introduced to the field of dental materials

in order to replace the metal-ceramic restorations. Their composition, microstructure, and

mechanical properties will determine their clinical indications and beside these, manufacturing

technique and restoration design will also play a role in the successful application of ceramic dental

prostheses.

Dental structures and restorative materials are frequently vulnerable to the surrounding

environment. The oral environment is very challenging, due to chemical and thermal variations

combined with humidity (Pereira et al., 2015). Radiotherapy (RT), often used for the treatment of

malignant lesions in the head and neck region (Walker et al., 2011), may also affect the properties

of different substrates. RT utilizes ionizing radiation to damage the genetic material of malignant

cells, resulting in cell death (Kielbassa et al., 2006). However, as a side effect ionizing radiation

affects healthy oral tissues, compromising the patient’s quality of life due to permanent limitations

in oral function (Walker et al., 2011). A deleterious effect of RT on sound tooth structure has also

been reported (Kielbassa et al., 1997; Kielbassa et al., 2006). Therefore, after the diagnosis of head

and neck cancer (HNC) lesions, RT has to be carefully planned to minimize the side effects of RT

in the short-term (Kelly et al., 2013). Decayed teeth have to be restored, extensively compromised

teeth have to be extracted and metallic restorations also need to be removed (Beech et al., 2014;

Jham et al., 2008).

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There is a possibility that restorations in the field of irradiation will have their physical and

mechanical properties affected after completion of the treatment. Composite resin restorations, for

example, have a reduced lifetime after RT (De Moor et al., 2011). Bond strength of composite

resin to dentin is another property that can be significantly affected by RT (Catelan et al., 2008;

Gonçalves et al., 2014). Amongst the indirect restorative materials, zirconia is gaining popularity

due to properties such as high flexural strength, high toughness, and dimensional stability (Piconi

& Maccauro, 1999). These make zirconia the material of choice for posterior indirect restorations

and extensive rehabilitations (Bona et al., 2015; Chen et al., 2016). The high mechanical properties

of zirconia are related to the transformation toughening mechanism of the tetragonal phase (Garvie

et al., 1975). Transformation toughening is a consequence of the local transformation of tetragonal

(t) into monoclinic (m), which generates compressive stresses that will help to seal microcracks

and prevent them from propagating into the bulk of the material (Hannink et al., 2000). However,

a severe and uncontrolled t-m transformation caused by a process known as low temperature

degradation (LTD) can compromise the mechanical properties of zirconia (Kim et al., 2009;

Pereira et al., 2015). So, the metastability of the tetragonal phase in the challenging oral

environment is critical and has been assessed by clinicians and researchers (Chevalier et al., 2004;

Wille et al., 2018).

Another limitation of zirconia is its opacity, which compromises the final esthetic of a

restoration when zirconia is used in a monolithic configuration. To overcome this limitation,

different zirconia-based materials have been developed. As a general rule, it seems that more

opaque materials have high mechanical properties, while the more translucent ones are reported to

have low mechanical properties (Harada et al., 2016). Changes in chemical composition and

crystalline structure have been applied to Y-PSZ to improve light transmittance and minimize

scattering (Gomes et al., 2018; Zhang, 2014), but how those changes would affect the stability and

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mechanical performance of zirconia under RT is not known. Therefore, the mechanical and

esthetic properties of zirconia-based materials will be evaluated after ionizing irradiation to see the

possible effect of RT on the performance of zirconia.

1. Dental ceramics 1.1 History of dental ceramics

Fabrication of tooth restorations was a challenge for many centuries. People tried to

overcome this problem by using different minerals and procedures to improve the strength of the

material. Alexis Duchateau, a French chemist, introduced ceramics to dentistry when he

successfully replaced his ivory dentures with porcelain in 1774 (Johnson, 1959). The introduction

of porcelain into Europe in the late 18th century accelerated the use of ceramics in dentistry.

In 1808, in Paris, Fonzi presented porcelain teeth that contained platinum pins (Kelly et al., 1996).

Their esthetic and mechanical properties provided a major advance in prosthetic dentistry. In1886,

the porcelain jacket crown was developed, based on a feldspathic composition, and the basic

composition is still used today in a slightly modified structure (Kelly et al., 1996).

In the early 1950, MacCulloch was the first to use glass ceramics in dentistry when Dicor ceramic

was introduced to the dental field, which was a micaceous glass-ceramic (45% volume glass and

55% crystalline tetra-silicic mica) processed by a combination of conventional lost-wax

investment techniques and glass casting (McLean et al., 2001).

In 1965, porcelain fused to metal (PFM) crowns were produced. The bond between the

metal and porcelain prevented the formation of stress cracks. In the same year, the addition of

leucite to porcelain formulations improved the coefficient of thermal expansion and allowed for

the fusion to certain gold alloys to form complete crowns and fixed partial dentures (FPDs) (Zhang

& Kelly, 2017). In 1965, McLean pioneered the concept of adding Al2O3 to feldspathic porcelain

to improve mechanical and physical properties of dental ceramics, and aluminous cores were

4

fabricated in 1968. Despite the enhanced mechanical properties, the material was not strong

enough for the fabrication of posterior all-ceramic FPDs (Schwickerath, 1986).

Several strategies have been developed to improve the strength and esthetic of dental

ceramics over the past two decades. These approaches focused mainly on enhancing the

mechanical and optical properties by changing the crystalline phase in the glassy matrix. Also, the

particle size and its distribution can lead to overall better strength of ceramic materials (Fairhurst,

1992). In addition, enhancing the mismatch in thermal coefficients expansion can cause localized

compressive stresses at phase boundaries improving the overall fracture toughness of the ceramic

material (Seghi et al., 1995).

In 1989, In-Ceram Alumina glass-infiltrated ceramics were introduced, with potential to be

used for three-unit FPDs. In 1991, leucite-reinforced glass ceramics were introduced (Empress1)

and were indicated for veneer, onlays, inlay bridges, and single unit restorations (Sorensen et al.,

1998).

In 1998, the development of a lithium disilicate glass-ceramic was a major breakthrough

since mechanical properties were significantly better, and esthetic requirements could be also met

(Fabianelli et al., 2006; Harada et al., 2016; Valenti & Valenti, 2009). Further efforts to enhance

the strength of ceramic cores were made by adding leucite, or zirconium dioxide crystals to

conventional feldspathic porcelains. However, these improvements still did not meet the

requirements for the fabrication of posterior FPDs.

Alumina- and Zirconia-based ceramics are the most recent core materials developed for

all-ceramic crowns and FPDs. Zirconia has superior mechanical properties and can be used for

posterior and also anterior single crowns, three units’ bridges, inlay, onlays, and implant abutments

(Malkondu et al., 2016). Zirconia was first introduced in the biomedical sciences in the early

1960s. Its application further extended to orthopedics in the 1980s (Chevalier, 2006), and then to

5

dentistry approximately 10 years later (Denry & Kelly, 2008). The composition of zirconia used

in dentistry is Yttria-tetragonal zirconia polycrystal (Y-TZP). Yttria is added to stabilize the

tetragonal phase at room temperature and prevent transformation of tetragonal phase to the

monoclinic phase upon cooling after sintering (Hannink et al., 2000; Manicone et al., 2007). Y-

TZP presents a highly unique characteristic named “transformation toughening”, which is the real

key factor to the applicability of zirconia-based materials in dentistry. This phenomena ensures

that the zirconia will has higher fracture resistance than any other ceramic materials (Garvie et al.,

1975).

1.2 Classification of all-ceramic systems

High strength ceramic materials in dentistry can be classified in three major groups

according to their chemical structure: predominantly glassy, particle-filled glasses and

polycrystalline ceramics (Kelly et al., 1996; Krämer et al., 2006; Raigrodski, 2005).

1.2.1 Predominantly glassy materials

These are dental ceramics with potential to mimic the optical properties of enamel and

dentin. Glasses are 3-D networks of atoms having no regular pattern to the spacing (distance and

angle) between nearest or next nearest neighbors. Glassy ceramics also have long firing ranges of

temperature and resist slumping if temperatures rise above optimal and are extremely

biocompatible (Fairhurst, 1992; Giordano 2nd, 2000; Kelly & Benetti, 2011).

1.2.2 Particle-filled glasses

Particle-filled glasses are a glass ceramic that contains filler particles which are added to

improve the mechanical properties. These have an advantage in terms of bonding with a crown

since when they are etched, a micro-retentive pattern is created, making the restoration bondable.

Filler crystalline particles that are currently used include leucite, mica and also lithium disilicate

(Giordano 2nd, 2000; Gracis et al., 2015; Shenoy & Shenoy, 2010).

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1.2.3 Polycrystalline ceramics

Polycrystalline ceramics are monophasic materials with dense particles and no glassy

components. They are generally much stronger than glassy ceramics. Pure polycrystalline oxide

ceramics have only been in clinical use for about 20 years (Bona et al., 2015). Alumina and

Zirconia are the only types of polycrystalline ceramics that are applicable to be used in dentistry

as restorative materials due to their ability to withstand large stresses during mastication in the

mouth and their white appearance (Kelly & Benetti, 2011; Piconi & Maccauro, 1999).

2. Monolithic zirconia

Zirconia can be used as a high strength core that is covered by a translucent, feldspathic

porcelain veneer. This helps to mask the opaque color of zirconia in order to create optimal

esthetics. However, high incidence of chipping and delamination of the veneer layer has been

reported (Kim et al., 2009; Zhang et al., 2012c). Therefore, in order to eliminate the drawbacks of

the veneering layer and reduce the risk of fracture (Rinke & Fischer, 2013), more translucent Y-

TZP materials have been developed to be used in a monolithic configuration (Jiang et al., 2011).

Monolithic restorations are manufactured using computer-aided design/computer-aided

manufacturing technology (CAD/CAM). Further to the elimination of chipping related failures,

the amount of removal of sound tooth structure is reduced due to the thinner restorations produced

(Rinke & Fischer, 2013; Stawarczyk et al., 2013).

2.1 Structure and compositions of monolithic zirconia

Zirconia has received considerable attention in dentistry due to its biocompatibility and

high mechanical properties such as fracture toughness, flexural strength, and fatigue resistance

(Chevalier, 2006; Hannink et al., 2000). The arrangement of the atoms in zirconia is characterized

by different crystallographic structures, a property known as polymorphism. The crystals of

7

zirconia are: monoclinic (m), tetragonal (t), and cubic (c) (Manicone et al., 2007). These phases

are based on thermal stability. The m phase stays stable up to 1170°C. Above 1170°C, it transforms

from m into t phase up to 2370°C. Above 2370°C and until the melting point the c phase is present

(Piconi & Maccauro, 1999). Upon cooling, the inverse sequence of events can be observed.

Therefore, when zirconia is sintered in the 1450-1550°C range the crystals are in the tetragonal

state. Upon cooling a reverse transformation occurs when the temperature reaches the 1170°C

threshold, with t phase going back to m phase in a process known as t-m transformation. This

causes a volumetric expansion of grains of about 4-5%. This granular expansion maximizes

stresses on zirconia’s crystals that will lead to crack propagation and fracture (Kisi & Howard,

1998). Furthermore, the tetragonal phase is desirable at room temperature to maximize the

mechanical performance of the material (Chen et al., 2016). In order to improve the thermal

stability of the tetragonal phase at room temperature, metallic oxides such as MgO, CaO, or Y2O3

are added to ZrO2, yielding to better mechanical performance and high fracture resistance (Christel

et al., 1989).

2.2 General properties of zirconia 2.2.1 Transformation toughening

As previously mentioned, the high mechanical properties of monolithic zirconia are related

to the transformation toughening mechanism (Garvie et al., 1975). This mechanism is triggered by

localized stresses generated by microcracks, which induce crystalline phase transformation of

metastable tetragonal grains adjacent to the defect into monoclinic crystal structure. T-m

transformation leads to a granular expansion that can seal microcracks hindering them from

propagating into the bulk of the material (Hannink et al., 2000). As a consequence, zirconia is

8

reported to have a low failure probability (Abdulmajeed et al., 2017; Aboushelib et al., 2016;

Conrad et al., 2007).

2.2.2 Low-temperature degradation

Although the transformation toughening mechanism could enhance the mechanical

performance of zirconia, a severe and uncontrolled t-m transformation caused by a process known

as low-temperature degradation (LTD) can compromise the mechanical properties of zirconia

(Kim et al., 2009). This degradation occurs due to the instability of the tetragonal phase at room

temperature in a humid environment (Borchers et al., 2010). The metastability of zirconia,

significantly contributing to its high strength, also makes it susceptible to aging in the presence of

moisture (Chevalier, 2006; Deville et al., 2006; Nawa et al., 2014). The LTD mechanism has been

described by several studies (Chevalier, 2006; De Souza et al., 2017; Kohorst et al., 2012; Özcan

et al., 2016; Pereira et al., 2015; Piconi & Maccauro, 1999), and it is attributed to the reaction of

water with the Zr-O-Zr and the formation of zirconium hydroxides, which can accelerate crack

growth of pre-existing flaws and promote the t-m phase transformation (Pereira et al., 2015).

Another explanation is that the diffusion of water into the zirconia grains occurs through filling

the oxygen vacancies and causes stresses in the crystalline network, which then disorganizes the

structure of the material leading to surface degradation (Lughi & Sergo, 2010; Pereira et al., 2015).

2.3 Main applications of zirconia in dentistry

The unique mechanical properties and biocompatibility of zirconia has motivated

substantial biomedical research since 1970s into how to use zirconia in medicine and dentistry

(Chen et al., 2016; Garvie et al., 1975; Manicone et al., 2007). Zirconia use in dentistry was

introduced because of its white color and high mechanical properties, aiming to replace the

metallic substructure of PFM restorations (Prestipino & Ingber, 1993; Yildirim et al., 2000), fixed

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partial dentures (Sturzenegger et al., 2000; Tinschert et al., 2001), orthodontic brackets (Keith et

al., 1994), and endodontic posts/dowels (Koutayas & Kern, 1999; Meyenberg et al., 1995). In a

review of clinical applications of zirconia, Manicone et al. evaluated the short-term clinical

performance of zirconia in posterior multi-unit FPDs, and they mentioned that zirconia could be

used both in anterior and posterior clinical applications (Manicone et al., 2007).

2.4 Different generations of monolithic zirconia in dentistry 2.4.1 First generation of zirconia (3Y-TZP) Adding Yttria (Y2O3) to the zirconia composition as stabilizer resulted in the development

of yttria-stabilized tetragonal zirconia (Y-TZP). This basic composition is also known as

conventional zirconia, which has become a successful material for application in dentistry (Denry

& Kelly, 2008; Jeong et al., 2002). This generation of 3Y-TZPs contained 0.25 wt% alumina

(Al2O3), which could stabilize the tetragonal phase and increase the densification of sintered

zirconia (Chen et al., 2008). The flexural strength of this generation reaches 1200 MPa (Zhang et

al., 2013b). It was mainly used as a core in porcelain-veneered crowns. The tiny crystal structures

of this material lead to low scattering of light, resulting in high opacity (Bona et al., 2015;

Christensen, 2009). Therefore, the veneer layer was used to enhance the esthetic of the restoration

by mimicking the optical properties of the tooth structure (Kelly, 1997; Kelly, 2004).

Despite the enhanced strength of this generation, clinical studies indicated a high incidence

of chipping and delamination of the veneer material, which has limited the longevity of restorations

(Christensen, 2009; Larsson & Vult von Steyern, 2013; Pang et al., 2015). The difference in the

coefficients of thermal expansion (CTE) of the framework zirconia and veneering porcelain

resulted in tensile stresses at the interface between zirconia and veneer layer. These tensile stresses

10

along with the external compressive stresses from the loading forces during the mastication process

led to delamination and fracture (Heintze & Rousson, 2010; Stawarczyk et al., 2017).

2.4.2 Second generation of zirconia (monolithic 3Y-TZP)

The second generation of zirconia was introduced between 2012 and 2013. It was

developed to be used in a monolithic configuration to improve the esthetic of the restorations.

Monolithic zirconia is considered an excellent alternative to the conventional porcelain veneered

zirconia restorations (Lameira et al., 2015). It is more translucent and does not need a porcelain

veneer coverage. Thus, manufacturing costs may be reduced by milling of full anatomical contour

restorations by CAD/CAM technology. In this generation, the alumina content was decreased,

allowing for more transmission of the light, and porosities were eliminated with the sintering

temperature increasing from 1350 °C to 1500 °C. This small change in the materials’ composition

enhanced optical properties, while maintaining the toughening mechanism (Sulaiman et al.,

2015a). Another approach was made by the modification of the sintering parameters of zirconia

(Stawarczyk et al., 2017). The changes include the sintering temperature, the dwell time, and

heating rate. Higher sintering temperatures lead to larger particle size, which in turn improved the

translucency but compromised the mechanical properties of the material (Jiang et al., 2011). These

findings have been confirmed by many in vitro studies which correlated higher translucency with

inferior mechanical properties of 3Y-TZP materials (Aboushelib et al., 2016; Christel et al., 1989;

Stawarczyk et al., 2016a).

2.4.3 Third generation of zirconia (5Y-PSZ)

The third generation of zirconia was introduced in 2015. The goal behind introducing this

generation was to improve a zirconia’s translucency to the level of translucency of restorations

fabricated from glass-ceramic materials. The amount of yttria content was increased to 4 mol%

(4Y-PSZ) or 5 mol% (5Y-PSZ) to produce a partially stabilized zirconia, with increased amounts

11

of cubic (c) phase (Stawarczyk et al., 2017). This improved translucency, but strength and

toughness were reduced because cubic zirconia does not undergo stress-induced transformation

(Zhang et al., 2016). The larger particle size of the cubic phase renders the material less porous,

which lead to less light scattering and therefore more translucency of the material (Zhang, 2014).

Mechanical properties such flexural strength and fatigue resistance are expected to decrease due

to the presence of the cubic phase, which minimizes the toughening mechanism based on t-m phase

transformation. A recent study reported that this generations has higher translucency than other

zirconia generation, but still not higher than lithium disilicate glass-ceramics (Harada et al., 2016).

Studies evaluating the third-generation zirconia are scarce and more research is needed in this area.

3. Characteristics of monolithic zirconia Zirconia shows mechanical properties that are similar to stainless steel (Piconi &

Maccauro, 1999), such as high flexural strength and fracture toughness (Bona et al., 2015). These

characteristics enable the manufacturing of FPDs with reduced thickness. To predict the long-term

performance of dental materials prior to clinical use (Aboushelib & Elsafi, 2016; Silva et al.,

2010b), which are need to reliable methods to predict the mechanical behavior of zirconia before

being used in the dental clinic use, their mechanical properties need to be investigated thoroughly

(El-Korashy & El-Refai, 2014; Guazzato et al., 2002). Flexural strength and fatigue resistance are

some of these properties assessed to estimate the reliability of dental materials (Pereira et al.,

2015).

3.1 Flexural strength

Flexural strength is a mechanical parameter that measures the materials’ resistance to

bending prior to failure and it is considered a meaningful and reliable parameter to evaluate

ceramics as they are much weaker in tension than compression (Della Bona & Kelly, 2008;

Egilmez et al., 2014). It is a fracture-related mechanical property and it is considered to be a

12

measure of the resistance of restorations to tensile forces (Aboushelib & Wang, 2010; Sunnegårdh-

Grönberg et al., 2003).

High flexural strength is desired due to the large masticatory stresses restorations are

exposed to in the oral mouth (McCabe & Walls, 2013). Materials with high flexural strength

provide restorations with less susceptibility to bulk fracture (Sunnegårdh-Grönberg et al., 2003).

Many in vitro studies of Y-TZP reported flexural strength values ranging from 900 to 1200 MPa

(Christel et al., 1989; Raigrodski, 2004; Siarampi et al., 2014).

In a study by Zhang et al., monolithic zirconia was found to have superior chipping and

fracture resistance compared to lithium disilicate and veneering porcelain (Zhang et al., 2013a).

The flexural strength of anatomic contour implant-supported zirconia of crowns was also reported

to be significantly higher than that of lithium disilicate and composite resins (Zhang et al., 2016).

With these superior mechanical properties, monolithic zirconia is considered to be the most

reliable material to be used in dental application (Bona et al., 2015).

3.1.1 Testing methods of flexural strength

Many studies have evaluated the flexural strength properties in dental ceramics by using

different testing methodologies (Aboushelib & Wang, 2010; Pittayachawan et al., 2007;

Stawarczyk et al., 2016b). The most common methods used for this purpose are either uniaxial

(e.g., three-point bending, or four-point bending) or biaxial flexure test (e.g., piston-in-ring, ball-

on-ring, or ring-on-ring) (Aboushelib & Wang, 2010; Pittayachawan et al., 2007; Stawarczyk et

al., 2016b). The strength data obtained by these different tests is not comparable and can be

affected by many factors such as specimen’s geometry (disc or bar samples), test methodology

(surface condition, stress rates), and thickness and dimensions of the samples. Therefore, the

extrapolation of strength data to clinical performance should be consider cautiously (Kelly et al.,

1996).

13

Three-point and four-point bending tests have been commonly used for measuring the

flexural strength of dental ceramics (Aboushelib & Wang, 2010; Awada & Nathanson, 2015; Nam

& Park, 2018), due to the simplicity of samples’ preparation and the ease to perform the test.

Additionally, no sophisticated sample grips are required. Also, the test results can be used as initial

load values for the fatigue test. For example, to perform a fatigue test like the staircase , the

determination of the initial load using a flexural strength test is required (Polli et al., 2016). The

uniaxial three-point bending test is performed by concentrating the load in one point at the center

of the sample, and it is considered a suitable estimate to the performance of restorative materials

(Manhart et al., 2000; Yap et al., 2000). According to the ISO standard for flexural strength of

ceramics, both the biaxial piston-on-three-balls test, and the uniaxial three-point bending test are

equally recommended (ISO, 1992).

3.2 Fatigue behavior

Fatigue failure may be defined as the cumulative damage triggered by cyclic forces. It is a

slow but steady process that may lead to the failure of even the strongest materials available

(Wiskott et al., 1995).

In the other words, fatigue strength is the stress that the material can resist in the long-term

in a given environment. The chewing process in the oral environment is an example of this

mechanical challenge. Studying the fatigue behavior of dental materials allows the understanding

of how resistant a material is under infinite cyclic loading prior to fracture (Polli et al., 2018; Zhang

et al., 2013b). The sub-critical crack growth of pre-existing defects in zirconia materials, triggered

by cyclic loading in a humid environment, is one type of failure that is developed through an

accelerated fatigue test (Kelly et al., 2017; Wiskott et al., 1995). Until now, data comparing the

fatigue behavior and survival rates of different zirconia generations is limited.

14

3.2.1 Fatigue test parameters

Fatigue test involves many variables such as the test loading environment (Chevalier, 2006;

Studart et al., 2007a), sample’s design, and the processing of the material. To evaluate the

material’s propensity to SCG, the test environment needs to be performed in water or artificial

saliva (De Aza et al., 2002). The geometry of the specimens can influence the force distribution,

leading to the development of either compressive or tensile stresses during service (Studart et al.,

2007b). Although using anatomically-shaped specimens closely simulate the real situation,

standardized bar-shaped specimens allow for accurate reproducibility and better control of the

variables under investigation (Denry & Kelly, 2008). The processing of the ceramic, which

involves the fabrication process from powder, sintering, to machining and finishing, also has a

profound effect on the stress distribution during service (Luthardt et al., 2004). For example,

grinding may introduce deep surface flaws, which act as stress concentrators and become strength

determining if their length largely exceeds the depth of the grinding induced surface compressive

layer (Kosmač et al., 1999).

3.2.2 Fatigue testing methods

Various methodologies are available for the simulation of the mechanical fatigue. One of

these approaches is called S-N curve, which is obtained by subjecting the specimen, like a crown,

to cyclic fatigue using different loads until fracture. The number of cycles (N) to fracture is

recorded and plotted against the stresses (S) to get the S-N curve (Kelly et al., 2017; Scherrer et

al., 2011). This method helps to determine multiple stress levels during test. However, it requires

a large number of specimens (Kelly et al., 2017).

Step-stress is among the fatigue tests that are used for dental ceramic. In this approach,

each specimen is subjected to time varying stresses, which means that the magnitude of load

changes after a period of time for the same specimen, until failure occurs, or the test is suspended

15

(Borba et al., 2013). Another method to measure the fatigue of the material is called “staircase”,

in which the specimen is subjected to a specific load for a number of cycles (Dixon & Mood,

1948). If the specimen fails, the load is decreased by one-step and another sample is loaded for the

same predefined number of cycles. If it does not fail, the load is increased by the step size for the

next specimen and so on. The purpose of this method is to obtain a value near the survival limit

stress below which failure never occurs, even for a large number of loading cycles (Nelson, 1980).

The number of specimens required for the staircase method is lower than for the S-N curve test,

and reliable determinations to predict the fatigue strength of the material can be obtained (Collins,

1993; Maennig, 1975). Thus, this method is known to be fast and precise to estimate the fatigue

limit of brittle materials with low variability (Collins, 1993).

3.2.3 Studies of fatigue behavior of monolithic zirconia in dentistry

Zirconia-based materials undergo fatigue under functional loading in the oral environment,

which gradually reduces their strength (Kohorst et al., 2008; Studart et al., 2007b). Repeated

contact with teeth during mastication can damage the surface of the material and cause the

accumulation of defects, which generate tensile stresses within the zirconia crown, accelerating

the fatigue process and leading to catastrophic failure over time (Zhang et al., 2013b). Clinical

outcomes indicate that the major cause of fracture occurring in dental crowns is fatigue failure

(Wiskott et al., 1995). A systematic review has found that monolithic zirconia crowns are

considered a promising option in the implant-based rehabilitation of edentulous patients, with high

success in the short-term (12 months) (Abdulmajeed et al., 2016). One study evaluated the fatigue

strength of different ceramic materials indicated for monolithic restorations and reported high

fatigue strength of translucent monolithic zirconia (370.02 MPa), in comparison to other ceramic

materials used such as lithium disilicate (175.20 MPa), and feldspathic ceramic (50.01MPa)

(Nishioka et al., 2018).

16

3.3 Optical properties

Mimicking the appearance of the natural dentition requires knowledge of the optical

behavior of teeth, restorative materials and the science of color perception. Translucency is

considered one of the important factors responsible for matching the color of natural teeth with

restorative materials (Brodbelt et al., 1980; Watts & Cash, 1994). Translucency is defined as the

property of a material by which a major portion of the transmitted light undergoes scattering

(Hunter et al., 1987). So, light scattering is the property that determines the level of translucency

of a dental ceramic material.

3.3.1 Parameters that influence the translucency of zirconia

Effort has been done to improve the level of translucency of dental zirconia, and it is

described in various studies (Stawarczyk et al., 2017; Zhang, 2014). A number of parameters can

adjust zirconia’s translucency such as particle size, sintering temperature, and the amount of

stabilizer (Zhang, 2014).

Small primary particle sizes in the range of 70 to 100 nm may improve translucency due

to more scattering of the light absorbed (Jiang et al., 2011; Yamashita & Tsukuma, 2011; Zhang,

2014). Some studies suggested that small grain size could also enhance light transmission and

optical properties of zirconia ceramic (Casolco et al., 2008; Yamashita & Tsukuma, 2011; Zhang

et al., 2012b).

Increasing the final sintering temperature of dental zirconia may also improve

translucency. For example, one study suggested that the optimal sintering temperature of zirconia

is between 1,450-1,500°C, when full densification occurs, which was increased from 1,350°C as

original temperature. The elimination of pores and flaws was obtained by this change, and allow

the material to scatter more light (Jiang et al., 2011; Zhang, 2014).

17

Increasing the concertation of the stabilizing oxides-yttria also improves translucency by

increasing the amount of cubic phase. Isotropic cubic phase has property that lead to the absence

of light scattering from grain boundaries (Alaniz et al., 2009; Zhang et al., 2012a). This is the

reason for the improved translucency of 5Y-PSZ (> 8 mol% of Y2O3) in comparison to 3Y-PSZ

(4 to 6 mol% of Y2O3) (Sulaiman et al., 2015b).

Another factor that plays a role in the translucency of Y-PSZ is the alumina content. High

alumina content makes the material more opaque (Harada et al., 2016; Sulaiman et al., 2015b).

This is due to the strong birefringent scattering, which induced by the distribution of alumina

dopant on the grain boundaries of zirconia (Matsui et al., 2006; Tsubakino et al., 1991; Zhang et

al., 2012a).

3.3.2 Measuring the translucency of zirconia

Translucency parameter (TP) is one of the most common parameters used to measure the

translucency of dental materials. TP can be defined as the color difference measured through the

thickness of a specimen over white and black background. Translucent materials have higher TP

value than opaque ones (Christensen, 2014). The following equation is used to calculate the TP

value of a material (Cie, 1932):

TP = [(LB* - LW*)2 + (aB* - aW*)2+ (bB* - bW*)2 ]1/2

Where: L* refers to the lightness, a* from redness to greenness, and b* from yellowness to blueness and it is measured against black (B), and white (W) backgrounds.

A spectrophotometer is used to measure the color differences, by determining the intensity

of reflected or transmitted light as a function of light source wavelength (Dozić et al., 2007). This

equipment is useful to quantify color differences between two or more tested specimens with

convenience and simplicity (Powers & Paravina, 2004), and can be applied in dentistry and other

fields of research (Chu et al., 2010; Paul et al., 2004). The principle behind it is that it measures

18

the amount of light energy reflected from the object at 1-25 nm intervals along the visible spectrum

(Chu et al., 2010; Khurana et al., 2007; Kielbassa et al., 2009). The main components of the

spectrophotometer are: the source of optical radiation, a measure of dispersing light, an optical

system for measuring, and a detector and a means of converting the light obtained to a signal that

can be analyzed and interpreted (Chu et al., 2010). It was reported that a spectrophotometer had

33% more accuracy and objective matching in 93.3% of the cases when compared with human

interpretation of color (Chu et al., 2010; Paul et al., 2002).

3.3.3 Evaluation of zirconia translucency in dentistry

Many brands of dental monolithic zirconia have been developed combining high

translucency materials and better mechanical properties by making changes in the material’s

microstructure and composition (Sulaiman et al., 2015a). Studies investigating the optical

properties of Y-TZP found that the smaller grain size allows for a desirable translucency with

high mechanical properties (Casolco et al., 2008; Trunec & Chlup, 2009). Fracture toughness for

example has been reported to reach its maximum usually at smaller grain size (Eichler et al., 2007;

Trunec, 2008). It is known that zirconia is less translucent than glass ceramics and the translucency

decreases with an increase on the material thickness. The TP values of human tooth as enamel and

dentin with a thickness of 1.0 mm have been reported from 18.7 and 16.4, respectively (Johnston,

2009). One study evaluated TP values of two types of monolithic zirconia, and found that TP

values of 3Y-TZP ranged from 14 and 16, while the values for 5Y-TZP were between 18 and 20,

which seems to be adequate to match the optical properties of natural teeth (Elsaka, 2019). This

indicates the current potential of high translucency zirconia to be used on areas where esthetics are

critical.

19

4. Radiation therapy (RT) 4.1 Principles of radiation therapy

Since 1990, the treatment of head and neck cancer has changed significantly. Different

strategies and protocols have been developed in order to improve loco-regional control (LRC) and

overall survival (OS). Radiation therapy (RT) is an efficient treatment for cancer. RT uses targeted

energy, for example X-rays or radioactive substances to destroy cancer cells, shrink tumors, and/or

alleviate certain cancer-related symptoms (Brahme et al., 2001). Radiation kills cells through

interactions with DNA and other target molecules, and by destroying the cancerous cells, the tumor

is minimized (Emami et al., 1991). One of the drawbacks of radiotherapy is that radiation is not

only limited to the cancerous cells site, but it may also damage healthy cells. The amount of

radiation used in radiation therapy is measured in gray (Gy) and it depends on the type of tumor

and the stage of cancer being treated. Commonly, the average total radiation dose used for head

and neck cancer is delivered in fractionated doses, 2 Gy per day, 5 days per week, to a total of 70

Gy over 7 weeks (Nguyen & Ang, 2002). The justification for applications in small daily fractions

is based on the radiobiology concept of “5Rs”: reoxygenation, redistribution, recruitment,

repopulation and regeneration. All these factors are related to biological contents of the human

cells and tissues (Mitchell, 2013).

4.2 Oral complication following radiation therapy

Radiation treatment in the head and neck region usually results in multiple oral

complications affecting the salivary glands, oral mucosa, bone, masticatory musculature, and

dentition (Kielbassa et al., 2006). The oral morbidities of radiation therapy include but are not

limited to an increased susceptibility to dental caries and periodontal disease. The most harmful

effects associated with RT include hyposalivation, mucositis, taste loss, trismus,

20

osteoradionecrosis, and radiation caries (Sroussi et al., 2017). Radiation caries lead to severe

destruction of the tooth enamel and dentin, compromising the quality of life of patients. This

indirect effect is due to irradiation-induced changes in salivary glands resulting in hyposalivation

(Kielbassa et al., 2006; Silva et al., 2009; Vissink et al., 2003). However, in vitro studies found

that RT can also lead to changes in crystalline structure and mechanical properties of enamel and

dentin (Al-Nawas et al., 2000; Kielbassa et al., 2006; Soares et al., 2011). Hardness (Kielbassa et

al., 2002), wear resistance (Davis, 1975), and tensile strength (Soares et al., 2010a) are some of

the properties compromised after exposure to doses greater than 60 Gy. The effect’s severity is

related to the dose used for the treatment (Reuther et al., 2003; Walker et al., 2011).

4.3 Effect of ionizing radiation on restorative materials

Resin-based composites and glass ionomers are widely used as restorative materials.

However, these restorations can be affected by many factors that will influence their clinical

performance and may lead to early failure of the restoration (Bernardo et al., 2007). RT affects

composite resin restorations and other direct restorative materials when irradiation is applied to

surrounding tissues and organs (Brahme et al., 2001; Curtis et al., 1991; von Fraunhofer et al.,

1989). One report has evaluated the effect of gamma radiation on the microtensile bond strength

of resin-based composite restorations before and after radiotherapy, and observed that bond

strength to enamel and dentin was adversely affected by irradiation (Gonçalves et al., 2014).

Chemical changes in the material structure may also affect the mechanical properties of composite

resin (Al-Nawas et al., 2000; Kielbassa et al., 1997; Soares et al., 2010a). The free radicals

produced in resin-based materials may induce chemical reactions, with ions, free radicals, and

excited molecules interacting to influence the material stabilization (Soares et al., 2010a). These

interactions may also affect the sealing ability and, consequently, the restoration longevity (Naves

21

et al., 2012). The flexural strength of composite resins can be compromised when the material is

exposed to a dose of 60 Gy or higher (Catelan et al., 2008). There is a clear lack of studies that

investigate the possible effect of RT on indirect restorative materials. Up to now, the interaction

between zirconia and ionizing irradiation has been only reported in other fields of research.

4.4 Possible interaction between ionizing radiation and zirconia

Zirconia has been considered a candidate for storage of nuclear waste, which requires

resistance to neutron exposure, gamma and beta radiation, and other extreme conditions (Sickafus

et al., 1999). Some early studies reported physical and mechanical changes on zirconia’s properties

after irradiation (Crawford Jr & Wittels, 1958; Degueldre et al., 1997). In terms of crystalline

stability, ionizing irradiation of zirconia can lead to phase transformations and structural

modifications that can significantly affect its physical and chemical properties (Ewing et al., 1995;

Hobbs et al., 1994; Schuster et al., 2009). Different levels of irradiation have been used to evaluate

the stability of monoclinic zirconia (m-ZrO2). Exposure to irradiation caused a reverse monoclinic-

to-tetragonal phase transformation due to the creation of defects at the cation and oxygen

sublattices. The study also demonstrated that the tetragonal phase could transform to cubic phase

upon irradiation with 340 keV Xe ions , and that is mainly due to atoms collisions and the creation

of lattice defects (Sickafus et al., 1999). The phase transformation from monoclinic to tetragonal

phase on zirconia (m-ZrO2) has been also reported on some other studies (Hémon et al., 1997;

Thomé, 2016).

Regarding mechanical properties, some studies found that ionizing irradiation can be

beneficial to enhance the mechanical properties of zirconia (Bekale et al., 2009; Motohashi et al.,

2004). Cubic yttria stabilized zirconia polycrystals (YSZ) was irradiated at room temperature with

940 MeV, and hardness and toughness were evaluated (Fleischer et al., 1990). Irradiated samples

22

had higher hardness and toughness. This improvement in the mechanical properties was likely due

to the residual compressive stresses that were introduced into the surface layer of samples as a

result from irradiation generated defects. A similar effect was observed by Motohashi et al. in 3Y-

TZP irradiated with 130 MeV. Compressive residual stresses occurred in the surface of irradiated

specimens, and an increase of both hardness and fracture toughness, was observed (Motohashi et

al., 2004).

However, the studies reported in this section used zirconia-based materials with a distinct

composition from those used in dentistry. The irradiation procedure and intensity of irradiation

energy are also different from the RT protocols applied to soft tissues. The variability between

methods and materials make it unlikely to understand how these findings would be correlated to

the effect of ionizing irradiation therapy in dental zirconia-based materials.

II. RATIONALE, OBJECTIVES & HYPOTHESES

1-Rationale

The success rate of radiation therapy to treat patients with head and neck cancer has

increased significantly throughout the years. However, this treatment may cause some oral

complications in salivary glands, dentition, bones, muscles and joints (Aguiar et al., 2009;

Kielbassa et al., 2006; Soares et al., 2010a). In addition, radiation may also affect restorative

materials causing structural alterations that are dose and material-dependent.

Zirconia-based materials are widely used in dentistry because of their superior mechanical

performance (Denry & Kelly, 2008). However, several factors can influence zirconia’s properties

and potentially lead to early failure of the restoration. The exposure of the metastable tetragonal

phase to the challenging oral environment is critical and has been discussed by clinicians and

researchers (Cales et al., 1994; Chevalier et al., 2004; Wille et al., 2018). The metastability of the

23

tetragonal zirconia is even more critical when changes are made in the material’s structure to

improve translucency (Zhang, 2014). Ionizing radiation may be one of these factors. Dental

restorations in the field of irradiation may receive a high amount of irradiation (Anscher et al.,

2005; Binger et al., 2008). The effect of ionizing radiation on the stability of the tetragonal phase

and, consequently, on the mechanical properties of dental zirconia is unknown, and has not been

investigated so far. However, studies in the fields of physics or materials’ engineering show the

development of irradiation related effects on both, cubic and monoclinic zirconia (Sickafus et al.,

1999; Thomé, 2016).

Given the high success rate of RT and the increasing longevity of patients diagnosed with

HNC, it is critical to understand the interaction between ionizing irradiation and restorative

materials, in order to characterize the performance of restorations over time and to define the best

treatment protocol for patients who will be treated by RT.

2- Objectives The objective of this study was to evaluate the effect of ionizing radiation on properties

of Y-PSZ materials, assessing its flexural strength, fatigue limit, and translucency.

3- Null (H0) hypotheses The study null hypotheses are:

1-Ionizing irradiation has no effect on flexural strength of either translucent or regular opacity

zirconia.

2- Ionizing irradiation has no effect on fatigue limits of either translucent or regular opacity

zirconia.

3- Ionizing irradiation has no effect on translucency parameters of either translucent or regular

opacity zirconia.

24

III. MANUSCRIPT (submitted to the J Biomed Mater Res B Appl Biomater on May 14/2019)

Title:

Effect of Ionizing Radiation on Mechanical Properties and Translucency of Monolithic

Zirconia

Authors:

Abdullah, A. Alshamrani, MSc

Faculty of Dentistry, University of Toronto, Toronto, ON, Canada

Grace, M, De Souza, DDS, MSc, PhD (corresponding author)

Faculty of Dentistry, University of Toronto, Toronto, ON, Canada

Address: 124 Edward St, #539, Toronto, ON, Canada, M5G1G6

25

Abstract: This study aimed to evaluate the effect of irradiation (RT) on mechanical properties and

translucency of monolithic. Yttria- stabilized zirconia (Y-PSZ) materials (14 mm × 4.0 mm × 1.5

mm) were divided in 4 experimental groups (n = 30): High-translucency/control (HT/C), high-

translucency/irradiated (HT/I), low-translucency/control (LT/C), low-translucency/irradiated

(LT/I). Irradiated specimens were submitted to a single dose irradiation of 70 Gray. Flexural

strength (n = 10) (FS - 3-point bending test), fatigue limits (n = 15) at 100,000 cycles (FLs -

staircase approach), and translucency (n = 5) (TP - dental spectrometer) were analyzed. X-ray

diffraction (XRD) and scanning electron microscopy (SEM) were used to characterize the

materials. FS and TP data were analyzed by one-way Analysis of Variance (ANOVA) and Tukey

HSD. FLs were analyzed using Dixon and Mood method, and Kaplan-Meier survival analysis. RT

affected FS of LT zirconia (p = 0.032) but not of HT zirconia (p = 0.86). FLs and TP of both

materials were not affected by RT (p > 0.05). Higher cubic content after RT was observed. In

conclusion, RT may affect flexural strength and crystalline content of zirconia-based materials,

but this effect was not observed under fatigue. Translucency of Y-PSZ restorations is also not

affected by RT.

Key words: Radiotherapy, Dental ceramics, Flexural strength, Fatigue resistance, Y-PSZ

26

INTRODUCTION

Head and neck cancer (HNC) patients are often treated with radiation therapy (RT), which

utilizes ionizing radiation to damage the genetic material of malignant cells, resulting in cell

death.1 However, ionizing radiation affects also healthy oral tissues, compromising the patient’s

quality of life due to permanent limitations in oral function such as salivary gland dysfunction,

taste change, neuropathic pain, difficulty in swallowing or chewing.2

RT is also known to affect the tooth structure and its mechanical properties in general.3

Hardness,4 wear resistance,5 and tensile strength6 of human enamel and dentin are some of the

properties that can be affected. Composite resin restorations and other direct restorative materials

have also been significantly affected when they remain in the field of irradiation.7-9 The effect of

ionizing irradiation on the mechanical performance of indirect restorations has not been discussed

in the literature yet.

Zirconia-based materials are ceramics widely used for prosthodontic rehabilitation because

of the combination of high mechanical performance, biocompatibility, and dimensional

stability.10,11 However, several factors can influence zirconia’s properties leading to early failure

of the restoration. Zirconia presents three different phases, namely monoclinic, tetragonal, and

cubic.12 Tetragonal zirconia stabilized by yttria is used in dentistry because of the high mechanical

properties of the crystalline assembly. However, the tetragonal phase is kept in a metastable state

and, in the challenging oral environment, can transform to the monoclinic state, which is stable at

room temperature.13,14 If severe and uncontrolled crystalline re-arrangement occurs in a process

known as low temperature degradation (LTD), it may compromise Y-PSZ mechanical

properties.15,16 This transformation occurs due to instability of the tetragonal phase at room

temperature and seems to be associated with water incorporation into the zirconia lattice.17,18

27

Dental restorations may receive high irradiation doses during the application of RT

depending on their location in the mouth,19,20 but the interaction between ionizing irradiation and

the metastability of the tetragonal phase of zirconia is not known. With the increasing demand for

all-ceramic restorations,21 and the affordability of computer-aided design & computer-aided

manufacturing (CAD/CAM) restorations, the number of patients receiving zirconia-based crowns

and prostheses in both, anterior and posterior regions, is increasing exponentially. Considering that

only in the United States 47% of all head and neck cancer lesions were treated with RT in 2016,

and that, by 2030, this number is expected to increase to 56%,22 the assumption that patients

making use of Y-PSZ crowns and prosthesis will receive RT for treatment of HNC is realistic.

Therefore, it is paramount to evaluate the effect of ionizing irradiation on mechanical and optical

properties of zirconia. So, the aim of this study is to investigate the effect of ionizing radiation

therapy on mechanical properties and translucency of zirconia-based materials. The study null

hypotheses are: 1- RT has no effect on flexural strength of Y-PSZ materials; 2 – RT has no effect

on fatigue limits of Y-PSZ materials; 3 - RT has no effect on translucency of Y-PSZ materials.

MATERIALS AND METHODS

Specimens preparation

The materials used in the present study are summarized in Table I. Two types of yttria-

polycrystalline stabilized zirconia (Y-PSZ) were used. A diamond blade (15 LC, Buehler, Lake

Buff, IL, USA) was used under low speed (400 rpm, Isomet 1000, Buehler Ltd) and constant water

flow to cut 60 bar-shaped specimens from both materials. After sintering according to the

manufacturers’ instructions, specimens were ground and polished up to 3 µm diamond suspension

and mastermet silica (0.6 µm). The final dimensions of the samples were 14 mm × 4.0 mm × 1.5

mm (ISO standard 6872-3 CD). After polishing, samples were exposed to an annealing cycle in a

laboratory chamber furnace (heating rate: 5 °C/min; dwell time: 2 h at 1,200 °C; cooling rate: 1

28

°C/min– CWF1300, Carbolite, UK) to relieve compressive strains added to the surface during the

polishing procedure.23

High translucency (HT) and low translucency (LT) zirconia specimens were divided into

two subgroups (n = 60): control (n = 30) and irradiated (n = 30). From each subgroup, 10 specimens

were assigned for flexural strength, 15 specimens for fatigue, and 5 samples for analysis of

translucency.

Irradiation of specimens

Y-PSZ specimens were placed at a depth of 5 cm in solid water phantom and between bolus

materials to simulate in vivo radiotherapy conditions and were irradiated with a single dose at the

Radiotherapy Clinic at Princess Margaret Cancer Centre (Toronto, ON), using a linear accelerator

(Elekta Ltd, Montreal, QC, Canada) with 6 MV energy. A single dose of 70 Gray (Gy), which is

the maximum average dose used for the treatment of head and neck cancer,24 was delivered.

Material

Brand

Composition

Manufacturer

Lot number

5Y-PSZ (HT)

Ceramill Zolid FX

ZrO2 + HfO2 + Y2O3: ≥ 99% Y2O3: 9.15 - 9.55% HfO2 :1.0 - 5.0% Al2O3 :0.0 – 0.5% Other oxides: 0.1%

Amann Girrbach

1606000-31

3Y-PSZ (LT)

IPS e.max Zircad

ZrO2 :87.0 - 95.0% Y2O3: 4.0 - 6.0% HfO2: 1.0 - 5.0% Al2O3: 0.0 - 1.0% Other oxides: < 0.2%

Ivoclar Vivadent

M42120

Table I: Description of the zirconia-based materials used in the current study

29

Mechanical test

Flexural strength: Three-point-bending test (ISO standard 6872-3 CD) was performed

using a universal testing machine (Instron 8501; Instron, Canton, Mass) (Figure 1). The bars were

placed on two supports (10 mm span) and loaded in the middle at a crosshead speed of 0.5 mm/min

until failure occurred. The flexural strength (monotonic failure load) was calculated considering

the load at fracture and the sample’s dimensions,25 which were verified with a digital caliper.

Fatigue limits: Fatigue resistance was analyzed using the staircase method.26 For that

purpose, samples were assembled in the same fixture used for the flexural strength and immersed

in distilled water at room temperature. The first fatigue stress level was set at 70 % of the flexural

strength values obtained by the three-point-bending test. If the specimen survived 100,000 cycles,

the stress level was increased by one increment (5 %) for next specimen. If the specimen failed

prior to completion of 100,000 cycles of loading, the load was decreased by one increment (5 %

of mean flexural strength) for the following cycle. This procedure was followed until all specimens

of each group were evaluated.27,28 Data analysis was based on the least frequent event of failure or

survival. The mean fatigue limit values (XL) and standard deviations (SD) were calculated.27

30

Translucency parameter analysis Five samples (n = 5) were analyzed per experimental group (thickness of 1.5 ± 0.05 mm).

Translucency of specimens placed over black and white backgrounds was measured with a

spectrophotometer (CR-300; Minolta Co. Ltd., Osaka, Japan) under the standard illuminant D65.

Data was recorded in CIELab color values and translucency parameter (TP) was calculated

considering color differences of specimens over the white and black backgrounds.29,30

Scanning electron microscopy

To measure the crystalline grain size distribution, zirconia specimens (one per group) were

thermally etched: Heating rate of 25 °C/ min; 1400 °C for 15 min dwell time; Cooling rate of 15

°C/ min. Specimens were sputter-coated with gold-palladium and examined using a scanning

electron microscope (SEM-JEOL 6610LV). At least 1,000 grains were analyzed using the linear

intercept method (ASTM E112 2013).

Figure 1. Assembly for both, three-point-bending and fatigue test.

31

Elemental composition analysis

One sample per zirconia material was characterized for surface elemental composition in a

microscope (JEOL 6610LV) coupled with an energy dispersive X-ray spectrometer (Philips, PW

3710, The Netherlands). The primary electron energy ranged from 5 to 20 keV. The other testing

parameters were set to WD: 15 mm; process time: 5 s; live time: 60 s; dead time: 30 – 40 %. Two

different areas were selected for each sample.

X-ray diffraction analysis

X-ray diffraction analysis (XRD) was employed to evaluate the crystalline composition of samples

after fatigue test and irradiation. The surface of zirconia specimens was scanned (one sample per

group) according to the following parameters: continuous scanning of 0.02o step size of 2 s per

step from 25o to 65o with Cu-Ka radiation (Philips, PW 3710, The Netherlands). The applied

voltage was 40 kV, using a 30-mA currency. Rietveld analysis was used to quantify the zirconia-

phase composition using Profex software.

Analysis of results

Data of flexural strength, fatigue limit, and translucency parameter were analyzed using one-way

ANOVA. Subsequent comparisons between groups were performed with Tukey honest significant

difference (HSD) at an overall significance level of 5 %. The fatigue test data was analyzed using

Dixon & Mood method to determine mean fatigue limits and standard deviation. The failure and

survival rates of the zirconia specimens were analyzed using Kaplan-Meier survival analyses.

RESULTS

Flexural strength

Mean and standard deviation (SD) of the flexural strength results are presented in Table II and

Figure 2. Comparison among groups with Tukey HSD test showed that LT/C samples (712.42 ±

32

77.04 MPa) presented flexural strength values significantly higher than all other groups (p <

0.001). FS of LT zirconia was significantly affected by irradiation: LT/I = 588.40 ± 143.82 MPa

(p < 0.05). Irradiation did not affect the flexural strength of HT zirconia: HT/C = 339.77 ± 88.08

MPa, HT/I = 306.44 ± 50.16 MPa (p = 0.856).

Fatigue limit

Table II presents mean and standard deviation for fatigue results. The staircase results are also

shown in Figures 3, 4, 5 and 6. The fatigue limit was reported as: LT/I: 464.31MPa = LT/C:

404.99 MPa > HT/I: 197.25 MPa = HT/C: 183.01 MPa, with LT materials presenting superior

performance than HT ones (p < 0.001). Although RT was responsible for a decrease in fatigue

limits for both materials tested, Tukey HSD test showed that the mean fatigue limit was not

significantly affected: p = 0.64 for HT zirconia; p = 0.55 for LT zirconia.

0

100

200

300

400

500

600

700

800

900

1 2 3 4

Load

(MPa

)

LT-C LT-I HT-C HT-I

Flexural Strength

b

cc

a

Figure 2: Bar graph illustrating the flexural strength results (in MPa) of the tested materials. Data are presented as mean ± standard deviation. Different lowercase letters indicate significant differences at 5% significance level.

33

Regarding the fatigue survival rates of tested materials, Kaplan-Meier and the Long Rank test

(Mantel-Cox) showed that there were no significant differences among the groups (p < 0.826)

(Figure 7). Table III presents the survival behavior and failure probability of the specimens on

each experimental group considering the number of cycles (100,000) until failure.

*Tukey HSD results (p< 0.05). Different lowercase letters in the same column indicate significant differences.

Figure 3. Staircase for LT-C. The red line indicates the mean fatigue limit (404.99 MPa), the black shaded elements indicate the surviving specimens, the white indicate failed specimens.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15350

400

450

500

550

Number of samples

Fatig

ue s

treng

th (

MPa

)

LT/C- fatigue strength 404.99 MPa

Material

Mean of flexural strength

(SD)(MPa)

Parameters for fatigue test (MPa)

Mean of fatigue

limit (SD) (MPa)

Strength decrease

(%) Initial strength

(70%of FS) Step size

(5% of FS)

LT-C 712.45 a (77.04) 498.33 35 404.99 (18.55) a 43.15 LT-I 588.40 b (143.82) 416.67 29 464.31 (27.24) a 21.08

HT-C 339.77 c (88.08) 230.00 17 183.01(16.75) b 46.13 HT-I 306.44 c (50.16) 213.33 15 197.25 (24.10)b 35.63

Table II. Mean values of flexural strength, initial fatigue limit, step size, fatigue limit data (in MPa) after 100,000 cycles and decrease from flexural strength to fatigue limit (%).

Specimen number

LT/C- fatigue limit 404.99 MPa

34

Figure 4. Staircase for LT-I. The red line indicates the mean fatigue limit (464.31MPa), the black shaded elements indicate the surviving specimens, the white indicate failed specimens.

Figure 5. Staircase for HT-RT. The red line indicates the mean fatigue limit (183.01MPa), the black shaded elements indicate the surviving specimens, the white indicate failed specimens.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15350

400

450

500

550

Number of samples

Fatig

ue s

treng

th (

MP

a)

LT/I - fatigue strength 464.31 MPa

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15160

180

200

220

240

Number of samples

Fatig

ue s

treng

th (

MP

a)

HT/C- fatigue strength 183.01 MPa

Specimen number

Specimen number

LT/I- fatigue limit 464.31 MPa

HT/C- fatigue limit 183.01 MPa

35

Figure 6. Staircase for HT-I. The red line indicates the mean fatigue limit (197.25MPa), the black shaded elements indicate the surviving specimens, the white indicate failed specimens.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15160

180

200

220

240

260

280

Number of samples

Fatig

ue s

treng

th (

MP

a)

HT/I - fatigue strength 197.25 MPa

Specimen number

HT/I- fatigue limit 197.25 MPa

36

Figure 7. Survival graphs obtained by Kaplan-Meier and Log-rank tests for number of cycles for failure (MPa). It indicates the fatigue behavior of each group: LT-C (blue line), LT-RT (green line), HT-C (yellow line), and HT-RT (purple line).

Table III. Summary of survival behavior of tested materials, and the probability of survival (%) for each group.

Groups Total n. failures

n. survival

Cycles for failure Survival rates (%)

LT-C 15 9 6 0 - 33,600 43.0% LT-I 15 7 8 120 - 25,000 54.0% HT-C 15 9 6 0 - 4,000 42.0% HT-I 15 8 7 0 – 18,500 cycles 44.0%

37

Translucency parameters

Mean and standard deviation (SD) of the translucency parameter results are presented in

Table IV. One -way ANOVA indicated that there was a significant difference between tested

groups (p < 0.001). Different TP value was observed between materials with different

compositions. As expected, HT zirconia (HT/C = 21.43, HT/I = 19.09) presented higher TP values

than the LT one (LT/C=13.1 LT/I = 12.9) (p < 0.001). However, there was no significant effect of

RT on TP (p > 0.05) for each material composition: p = 0.071 for HT zirconia and p = 0.99 for LT

zirconia.

Table IV. Mean (SD) translucency parameter values for the tested material.

Groups Mean (MPa) Standard deviation (SD)

LT/C 12.95 a 1.45 LT/I 12.80 a 0.97 HT/C 21.43 b 0.55 HT/I 19.09 b 2.05

*Tukey HSD results (p< 0.05). Different lowercase letters in the same column indicate significant difference.

EDS analysis

Figure 8a shows the chemical composition of LT 3Y-PSZ (IPS e.max Zircad) based on EDS

analysis, and Figure 8b shows the elemental composition for HT 5Y-PSZ. High translucency

zirconia presented higher contents of Yttria (HT – 5.63 wt%; LT – 1.89 wt%), and a high

concentration of Erbium oxide was also observed (HT – 14.02 wt%), which was not present in the

composition of the LT material. Alumina contents were similar in both materials: LT - 0.14 wt%;

HT – 0.17 wt%.

38

Crystalline size analysis

The average grain size of Y-PSZ specimens used in this study was calculated using the

linear interceptive count method. The results indicated that HT materials presented larger

crystalline grains, irrespective of RT treatment: the grain sizes were 0.374, 0.376, 0.57, 0.61 µm

for LT/C, LT/I, HT/C, and HT/I respectively (Table V). Figure 9 shows SEM images of the Y-

PSZ surface to demonstrate the crystalline structure of zirconia-based materials.

Table V. Comparative mean of grain size (µm), and standard deviation (SD) of zirconia materials used in the study.

Material Control Irradiated

Low Translucency (3Y-PSZ) 0.374(0.04) 0.376(0.04)

High Translucency (5Y-PSZ) 0.57 (0.10) 0.61(0.12)

Figure 8. Quantitative results of chemical composition of tested materials. a) LT- 3Y-PSZ (IPS e.max Zircad); b) HT- 5Y-PSZ (Ceramill Zolid FX)

a b

39

B

C

Figure 9. SEM images (original magnification ×10,000) of the bar-shaped samples indicating different

crystalline structures of zirconia materials with different levels of translucency: a) Low Translucency – Control; b) Low Translucency – Irradiated; c) High Translucency- Control; d) High Translucency - Irradiated. Similar crystalline composition was observed between a and b samples; c and d samples show large cubic grains.

A B

C D

40

XRD analysis Representative XRD patterns for HT zirconia (5Y-PSZ) and LT zirconia (3Y-PSZ) were quantified

by Rietveld analysis and the data is detailed in Table VI. XRD patterns indicated phase

transformation from tetragonal to cubic (t - c) after ionizing irradiation by approximately 20 wt%

for LT, and 8.7 wt% for HT.

Table VI. Crystalline phase composition of Y-PSZ materials used in this study.

DISCUSSION

Radiation therapy is the medical use of ionizing radiation as part of a treatment to control

or kill malignant cells.7 It is usually associated with clinical complications such as radiation caries,

xerostomia, osteonecrosis and trismus.2 The presence of dental restorations is one of the factors

that should be taken into consideration when patients undergo RT. Restorative materials may react

differently under RT, and therefore may cause some side effects that influence the quality of life

of patients. For example, metal fixed prostheses are recommended to be removed prior to RT

mainly due to a 33% dose enhancement caused by emission of secondary electrons.31This dose

enhancement is associated with mucositis.31 The possible interaction between zirconia as an

indirect restorative materials and ionizing radiation has not been investigated yet. Therefore, the

present study focused on evaluating the mechanical and optical performance of two dental

Groups

m-ZrO2 wt.%

t-ZrO2 wt.%

c-ZrO2 wt.%

LT/C 0.18 83.2 16.5 LT/I 0.40 63.1 36.5 HT/C 0 76.6 23.4 HT/I 0 67.9 32.1

41

zirconia-based materials for CAD/CAM use. Materials with two levels of translucency were

employed due to differences in composition and crystalline structure between them.32,33

The three-point bending flexural strength values were determined to be in the range of

721.45 MPa (LT/C) and 306.44 MPa (HT/I). These numbers are in agreement with previous

studies evaluating the mechanical performance of materials with different levels of

translucency.34,35 Analysis of the results indicated that there was a significant difference (p <

0.001) in FS values between LT (721.45 - 588.40 MPa) and HT (339.77 - 306.44 MPa) materials.

Fatigue resistance was also significantly affected (p < 0.001) by the materials’ composition (Table

II). The differences in the mechanical performance of materials with different compositions may

be explained by variations in yttria content. EDS results (Figure 8a and b) show that the yttria

content of HT (5Y-PSZ) is 5.63 wt%, while yttria content of LT (3Y-PSZ) is 1.89 wt%. The higher

amount of stabilizer on HT materials leads to a higher presence of cubic phase in the material’s

crystalline composition, which is confirmed by the results of the XRD analysis (LT/C: 16.5 wt%

of cubic phase; HT/C: 23.4 wt% of cubic phase) shown in Table VI. The higher incidence of cubic

phase may have affected the FS values of HT zirconia because it diminishes the capacity of the

material to be reinforced by the transformation toughening mechanism, due to the lower presence

of tetragonal phase.36 Another possible explanation for differences in the mechanical properties of

both monolithic zirconia is the average grain size. The SEM images in Figure 9 show the

differences in crystallographic size between 3Y-PSZ and 5Y-PSZ, with HT zirconia presenting

grains almost twice as large as the grains of LT materials (Table V). Smaller grains limit the size

of dislocations on the crystal grain boundaries, affecting the transposition of the stimuli from grain

to grain. Therefore, a higher stress rate is required to lead to deformation or fracture of ceramic

materials with smaller grains,37 having an effect on both, monotonic stress failure and fatigue

resistance, due to the more complex nature of crack propagation around smaller grains. Another

42

property reportedly affected by crystalline grain size of zirconia-based materials is surface

microhardness.34

The first null hypothesis of the study assumed that the flexural strength of zirconia-based

materials would not be affected by RT. Results of the Tukey HSD test (Table II) indicated that

ionizing radiation had a significant effect on flexural strength of LT (p < 0.05), but not on FS of

HT zirconia (p = 0.856). Therefore, the study first null hypothesis was partially accepted. The

second null hypothesis of the study assumed that fatigue limits of zirconia-based materials would

not be affected by RT. The results of Tukey HSD indicated that the mean fatigue limit values,

which ranged from 464.31 MPa to 183.01 MPa, were not affected by ionizing radiation (HT: p =

0.64; LT: p = 0.55). Therefore, this study failed to reject the second null hypothesis.

The significant effect of RT on FS of LT zirconia may be attributed to changes happening

in the crystalline structure. The XRD analysis of the crystalline content of zirconia revealed an

increase in cubic crystalline content in the range of 20 wt% for LT zirconia and 8.7 wt% for HT

zirconia after irradiation (Table VI). These results indicate that a tetragonal to cubic (t – c)

transformation took place after the specimens were exposed to 70 Gy irradiation and some theories

may explain the mechanisms behind this transformation. A significant effect of ionizing irradiation

on zirconia microhardness was reported as a result of residual compressive stresses generated by t

- c surface phase transformation, confirming the findings of the present study.38 Besides the t – c

transformation, the stress field associated with those changes can escalate to irradiation “defects”

due to localized vacancies developed, as previously reported in a study investigating 10 mol%

yttria-stablized zirconia.39 Another possible mechanism that may affect the crystalline structure of

zirconia is the accumulation of oxygen vacancies in irradiated zirconia. Some studies found that

the ionizing irradiation of zirconia-based materials can lead to a loss of oxygen atoms.40,41 The

importance of oxygen vacancies in stabilizing cubic and tetragonal zirconia was suggested in the

43

literature.42-44 For example, it was observed that by controlling the concentration of oxygen

vacancies tetragonal phase can be stabilized at room temperature.38 Therefore, monoclinic-to-

tetragonal, and tetragonal-to-cubic phase transformations can be triggered by increasing the

oxygen vacancy concentration.45 This correlation between oxygen vacancy and the phase stability

of zirconia has also been shown in other studies.42,46

In terms of translucency, the results of this study revealed that 5Y-PSZ (HT- Ceramil ZI)

had higher TP value than 3Y-PSZ (LT- IPS e.max Zircad). However, RT did not affect the

translucency parameter values of both, HT and LT zirconia (Table IV). Therefore, this study failed

to reject the third null hypothesis, which assumed that RT would not affect translucency of zirconia

materials. It has been shown that by increasing the yttria content the translucency of zirconia

materials is improved due to the higher incidence of cubic phase.47,48 The cubic phase is reported

as being optically isotropic, which decreases the light scattering from birefringent grain boundaries

and, consequently, improve translucency.49 It was, therefore, expected that the translucency of the

zirconia materials used in this study would increase after irradiation, given the higher amount of

cubic phase detected (Table VI), but this effect was not observed. It can only be hypothesized that

the ionizing irradiation caused further changes in the materials that were not detected by the

methods employed.

To the best of the authors’ knowledge this is the first study evaluating the effect of ionizing

irradiation on dental zirconia. Some of the limitations of the study are related to the application of

a single dose of 70 Gy for irradiation of specimens, which is different from the daily dose protocol

recommended to treat HNC lesions. Fractionated doses (2 Gy/day, 5 day/week, 7 weeks) are based

on a well-known concept called R5s: reoxygenation, redistribution, recruitment, repopulation and

regeneration. All these factors are related to biological mechanisms of the human cells and

tissues.50 However, it is expected that fractionated doses would not affect the properties of a

44

material with high crystalline content like zirconia. Another limitation of this study is related to

the fatigue test protocol and its relatively low number of cycles (100,000). However, studies have

shown that the main decrease on fatigue limits is noticed around the first initial 200 cycles, and

the effect is minimized after passing this limit.51-53 Therefore, one should not expect different

results with higher number of cycles. Also, it should be mentioned that the sample geometry (bar-

shaped), the standardized sample preparations, and the loading protocols do not reproduce the

clinical situation but are necessary to concentrate the analysis on the pure materials’ properties.

Thereafter, the present study brings evidence that the flexural strength and crystalline composition

of Y-PSZ based-materials may be affected when exposed to the ionizing irradiation treatment.

Further studies in this field are recommended.

CONCLUSION

Within the limitations of this study, the following could be concluded:

- Flexural strength of LT zirconia (3Y-PSZ) is affected by clinically-relevant ionizing radiation.

However, flexural strength of HT zirconia (5Y-PSZ) is not affected.

- The fatigue limits of zirconia-based materials is not affected by ionizing radiation, regardless of

the material composition.

- Ionizing radiation does not affect the translucency of zirconia-based materials (HT and LT).

- Ionizing radiation triggers crystalline changes in zirconia materials with different compositions.

Acknowledgments

This project was funded by King Saud University (Saudi Arabian Culture Bureau) under

the scholarship of the MSc student. Further expenses were covered by Dr. De Souza’s research

funds. Authors also acknowledge the help of Dr. Andrew Hope and Dr. Andrea McNiven,

Radiation Oncology Department, Princess Margaret Cancer Centre, Toronto, ON, Canada.

45

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51

IV. DISCUSSION

Radiation therapy is the medical use of ionizing radiation as part of a treatment to control

the growth or kill malignant cells (Brahme et al., 2001). There are many clinical complications

associated with RT such as radiation caries, xerostomia, osteonecrosis and trismus (Sroussi et al.,

2017). The presence of dental restorations is one of the factors that should be taken into

consideration when patients undergo RT. Restorative materials may react differently under RT,

and therefore may result in side effects that influence the quality of life of patients. For example,

metal fixed prostheses should be removed prior to RT because of a 33% dose enhancement caused

by the emission of secondary electrons (Thilmann et al., 1996). This dose enhancement is

associated with mucositis (Thilmann et al., 1996). The possible interaction between zirconia as an

indirect restorative material and ionizing radiation has not been investigated yet. Therefore, the

present study focused on evaluating the mechanical and optical performance of two dental

zirconia-based materials for CAD/CAM use. Materials with two levels of translucency were

employed due to differences in composition and crystalline structure between them (Nam & Park,

2018; Stawarczyk et al., 2017).

1) Material’s composition and structure

The three-point bending flexural strength values were determined to be in the range of 721.45

MPa (LT/C) and 306.44 MPa (HT/I). These numbers are in agreement with previous studies

evaluating the mechanical performance of Y-PSZ materials with different levels of translucency

(Marchionatti et al., 2019; Stawarczyk et al., 2016). Differences in mechanical performance of

materials with different compositions may be explained by variations in yttria content. EDS results

(Figure 8a and b) showed that the yttria content of HT (5Y-PSZ) was 5.63 wt%, while yttria content

of LT (3Y-PSZ) was 1.89 wt%. The higher amount of stabilizer on HT materials is associated with

higher concentration of cubic phase in the material’s crystalline composition, which was confirmed

52

by the results of the XRD analysis shown in Table VI (LT/C: 16.5 wt%; HT/C: 23.4 wt%). The

higher incidence of cubic phase may have affected the FS values of HT zirconia because it

diminishes the capacity of the material to be reinforced by the transformation toughening

mechanism (Zhang et al., 2016). It is well known that transformation toughening happens as a

consequence of tetragonal-to-monoclinic transformation. Therefore, materials with lesser amounts

of tetragonal phase are less capable of presenting this reinforcing mechanism.

The EDS results showed a high concentration of Erbium oxide in the high translucency

zirconia (HT – 14.02 wt%), which was not present in the composition of the LT material. Studies

have suggested that adding rare earth oxides like Erbium zirconia enhances esthetic outcomes by

providing the material with more tooth-resembling colors (Huang et al., 2007; Li et al., 2011).

Increased translucency and approximately 30% lower flexural strength when Er2O3 was added to

raw zirconia powder has been previously reported (Liu et al., 2010). Therefore, the presence of

Erbium oxide in the HT material may have also played a role in decreasing its FS, but the

underlying mechanism still needs to be investigated.

2) Effect of irradiation on mechanical properties

Ionizing radiation had a significant effect on flexural strength values of LT (3Y-PSZ). The FS

of LT/C was 712.42 MPa, and a value 18% lower was observed after irradiation (588.40 MPa).

The FS of HT materials was not significantly affected by irradiation. The fatigue limits (FL), which

ranged from 183.01 MPa to 446.31 MPa indicated that materials with different levels of

translucency had different fatigue behaviors. For example, the FL of LT zirconia (C - 404.99 MPa;

I – 446.31 MPa) were significantly higher than the FL of HT zirconia (C - 183.01 MPa; I – 197.52

MPa). While irradiation caused a numeric decrease on flexural strength values, it had a reverse

effect on FL of both materials, with a slight increase in numbers. However, it is important to point

out that the increase was not significant. The irradiated groups for both materials show less

53

decrease on FL comparing to the initial flexural strength (LT/I – 21.08%; HT/I – 35.63%). A more

prominent decrease in FL when compared to initial flexural strength was observed for control

groups of each material (LT/C - 43.15%; HT/C – 46.13%).

The average grain size (Figure 9) is a possible explanation for differences in the mechanical

properties of both monolithic zirconia-based materials. HT zirconia presents grains almost twice

as large as the grains of the LT material (Table V). Smaller grains limit the size of dislocations on

the crystal grain boundaries, affecting the transposition of the stimuli from grain to grain (Eichler

et al., 2007). Therefore, a higher stress rate is required to lead to catastrophic failure of ceramic

materials with smaller grains (Palmero, 2015). Crystal grain size may have an effect on both,

monotonic stress failure and fatigue resistance, due to the more complex nature of crack

propagation around smaller grains. Another property reportedly affected by crystalline grain size

of zirconia-based materials is surface microhardness (Stawarczyk et al., 2016). In the present

study, the failure analysis of crack origin showed that all samples investigated under SEM

fractured at the center of the bar-shaped specimens, with the crack origin being located on the

tensile side. There was no difference in the mode of failure between control and irradiated samples

of both materials.

3) Crystalline structure and irradiation

The XRD analysis of the crystalline content of zirconia revealed an increase in cubic phase in

the range of 20 wt% for LT zirconia and 8.7 wt% for HT zirconia after irradiation (Table VI).

These results indicate that a tetragonal to cubic (t – c) transformation took place after the specimens

were exposed to 70 Gy irradiation. Some theories may explain the mechanisms behind this

transformation. A significant effect of ionizing irradiation on zirconia microhardness was reported

as a result of residual compressive stresses generated by t - c surface phase transformation,

confirming the findings of the present study (Duh & Wu, 1991). Besides the t – c transformation,

54

the stress field associated with those changes can escalate to irradiation “defects” due to localized

vacancies developed, as previously reported in a study investigating 10 mol% yttria-stablized

zirconia (Bekale et al., 2009). Another possible mechanism that may affect the crystalline structure

of zirconia is the accumulation of oxygen vacancies in irradiated zirconia. Some studies reported

that the ionizing irradiation of zirconia-based materials can lead to a loss of oxygen atoms

(Edmondson et al., 2011; Zhang et al., 2010). The importance of oxygen vacancies in stabilizing

cubic and tetragonal zirconia was previously suggested (Eichler, 2001; Fabris et al., 2002; Guo,

1998; Karapetrova et al., 2001). For example, it was observed that by controlling the concentration

of oxygen vacancies tetragonal phase can be stabilized at room temperature. Therefore,

monoclinic-to-tetragonal, and tetragonal-to-cubic phase transformations can be triggered by

increasing the oxygen vacancy concentration (Badwal et al., 1993).

4) Translucency of monolithic zirconia

The translucency of Y-TZP can be adjusted by a number of parameters, such as crystalline content

and chemical composition. However, those changes are known to affect properties such as fracture

strength and fatigue resistance (Pereira et al., 2015). If the wavelength of the incident light and the

size of the grain are in a similar range, the light-scattering effect becomes significant and results

in lower translucency (Kim et al., 2013). When comparing the effect of the primary particle size

on zirconia’s translucency, 40 nm grains resulted in higher zirconia translucency than 90 nm (Jiang

et al., 2011).

The results of the present study revealed that 5Y-PSZ (HT- Ceramil ZI) had higher TP values than

3Y-PSZ (LT- IPS e.max Zircad). RT did not affect the translucency parameter values of both, HT

and LT zirconia (Table IV). It has been shown that by increasing the yttria content the translucency

of zirconia materials is improved due to the higher incidence of cubic phase (Sulaiman et al., 2015;

Zhang, 2014). Cubic phase is reported as being optically isotropic, which means that it decreases

55

light scattering from birefringent grain boundaries and, consequently, improves translucency

(Zhang & Lawn, 2018). It was, therefore, expected that the translucency of the zirconia materials

used in this study would increase after irradiation, given the higher amount of cubic phase detected

(Table VI), but this effect was not observed. It can only be hypothesized that the ionizing

irradiation caused further changes in the materials that were not detected by the methods that were

used in this in vitro study.

5) Study methodology

Dental restorative materials with high flexural strength are desirable due to the large

masticatory stresses that restorations are exposed to in the oral cavity (McCabe & Walls, 2013).

This will provide restorations with less susceptibility to bulk fracture (Sunnegårdh-Grönberg et

al., 2003). Many in vitro studies of Y-TZP reported flexural strength values ranging from 900 to

1200 MPa (Christel et al., 1989; Raigrodski, 2004; Siarampi et al., 2014). FS values of this study

were between 721.45 MPa and 339.77 MPa. The analysis of flexural strength was performed using

three-point bending test, based on the ISO specification 6872:2008. This method has been

commonly used for measuring the flexural strength of dental ceramics (Aboushelib & Wang, 2010;

Awada & Nathanson, 2015; Nam & Park, 2018). One of the advantages of this test is the simplicity

of samples’ preparation and the ease to perform the test.

The values recorded for flexural strength were also used in this study for the determination

of the fatigue initial load to be used in the staircase method (Polli et al., 2016). The staircase

method has a number of advantages over other methodologies such as S-N curve and step-stress.

The number of specimens needed for the staircase method is lower than for the other tests, and it

is considered a reliable method to predict the fatigue limit of the material due to the low variability

of the results (Collins, 1993; Maennig, 1975). The staircase method also allows researchers to

precisely estimate the fatigue limit at 50% failure probability (Dixon & Mood, 1948). A relatively

56

low number of cycles (100,000) was employed in the present study to evaluate fatigue resistance.

However, studies have shown that the main decrease on fatigue limits is noticed around the first

initial 200 cycles, and the effect is minimized after passing this limit (Amaral et al., 2016; Mitov

et al., 2011; Scherrer et al., 2011). Therefore, no effect of higher number of cycles has been

demonstrated on the analysis of fatigue limits of ceramic materials.

The test environment can also play a role on the performance of zirconia-based materials.

In the present study the fatigue tests were performed in distilled water at 22 °C. There are reports

showing a reduction in flexural strength of ceramic materials in water in comparison to a dry

environment, due to corrosion of the ceramic by water molecules, leading cracks to grow (De Aza

et al., 2002). No comparison has been made yet between fatigue cycling in distilled water or

artificial saliva. Since artificial saliva would resemble the natural condition better and the ions

present may affect the atomic links of zirconia, it is desirable to make this comparison in the future.

To the best of the authors’ knowledge this is the first study evaluating the effect of ionizing

irradiation on dental zirconia. One of the limitations of this study is related to the application of a

single dose of 70 Gy for irradiation of specimens, which is different from the daily dose protocol

recommended to treat HNC lesions. Fractionated doses (2 Gy/day, 5 day/week, 7 weeks) are based

on a well-known concept called R5s: reoxygenation, redistribution, recruitment, repopulation and

regeneration. All these factors are related to biological mechanisms of the human cells and tissues

(Mitchell, 2013). Fractionated doses were not used in the present study because biological tissues

were not involved.

57

V. CONCLUSION

Within the limitations of this study, it is possible to conclude that 70 Gray ionizing radiation

negatively affected the flexural strength of low-translucency zirconia but did not affect the FL of

HT zirconia. In addition, the fatigue limits and translucency were not affected by ionizing

radiation. Overall, LT zirconia presented superior mechanical performance than HT zirconia. An

increase in cubic phase content was observed for both materials tested after ionizing radiation.

58

VI. FUTURE DIRECTIONS

1- Our findings indicated that single dose ionizing irradiation (70 Gy) affected some of the

mechanical properties of zirconia-based materials. Therefore, future studies should focus

on investigating the combined effect of fractionated doses (2 Gy/day, 5 day/week, 7 weeks)

and fatigue, which may closely simulate the clinical application of zirconia-based

restorations.

2- The chemical characterization of both materials showed different concentrations of

chemical elements such as Erbium oxide and Ytrium oxide. Erbium oxide may have played

a role in decreasing FS of the HT material. So, further investigations using experimental

materials with and without Erbium oxide should be performed, to better understand its

effect on translucency and mechanical properties of dental zirconia.

3- Given the effect of ionizing irradiation of crystalline composition of zirconia, other

properties of irradiated zirconia should be investigated in the future, such as: wear,

roughness and surface hardness.

4- It is also necessary to investigate the effect of ionizing irradiation on other materials

recommended for indirect restorations. Lithium disilicate is one of those materials that has

not been investigated so far and is in high demand in the clinic.

59

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VIII. APPENDICES

Appendix I: Assembly for the measurement of the translucency parameter.

A B

A) Spectrometer (Minolta CR-300 chroma meter). B) specimen on white and black background.

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Appendix II: Scanning electron microscopy (SEM) images of the fractured slabs subjected to fatigue test: A) Low Translucency – Control; B) Low Translucency – Irradiated; C) High Translucency – Control; D) High Translucency-irradiated. The black arrows indicate the direction of crack propagation (dcp), and the surrounding hackle lines. The red dot indicated the origin of fracture for these samples was at the tensile side.

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A. XRD graphs depicting the peaks related to each specific crystallographic phase of low translucency – control material (LT-C).

B. XRD graphs depicting the peaks related to each specific crystallographic phase of low translucency – irradiated material (LT-I).

Appendix III: XRD graphs and crystalline content of selected samples.

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C. XRD graphs depicting the peaks related to each specific crystallographic phase of high translucency – control material (HT-C)

D. XRD graphs depicting the peaks related to each specific crystallographic phase of high translucency – irradiated material (HT-RT).

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E. XRD patterns for zirconia materials. HT-C (High Translucency - Control), HT-I (High Translucency-irradiated), LT-C (Low Translucency- control), LT-I (Low Translucency-irradiated). LT samples indicated more tetragonal peaks than HT samples, while the HT has more cubic peaks than LT.

87

67.45

25.44

5.631.36 0.12 0

0

10

20

30

40

50

60

70

80

ZrO2 O2 Y3O2 HfO2 Al3O2 ErO2

Wei

ght%

HT (5Y-PSZ)

A. I. quantitative results of chemical composition of the material tested. II. energy dispersive spectroscopy (EDS) analysis for high translucency 5Y-PSZ.

I II

Appendix IV: EDS analysis of both low and high translucency zirconia materials.

ZrO2 O2 Y3O2 HfO2 Al3O2 ErO2

88

a a

I

a

a

B. I. quantitative results of chemical composition of the material tested. II. energy dispersive spectroscopy (EDS) analysis for high translucency 3Y-PSZ.

II

70.41

25.94

1.89 1.62 0.14 00

10

20

30

40

50

60

70

80

ZrO2 O2 Y3O2 HfO2 Al3O2 ErO2

Wei

ght%

LT (3Y-PSZ)

ZrO2 O2 Y3O2 HfO2 Al3O2 ErO2

89

A. Equation used to calculate flexural strength

𝐹𝑆 = $%&'()*

where: P is the fracture load; L is the roller span (10 mm); B is the width of sample and D is the thickness of the sample.

B. Equations for determination of fatigue limits

XL = X0 + d (A/N) ± 0.5

SD = 1.62 d [NB - (A2/N2) + 0.029]

Where XL: the fatigue limit of the material. X0 : the lowest recorded failure stress (MPa). d : the fixed increment in MPa. N : the sum of failures or survivals occurring at the different stress levels, irrespective of the load applied. A : the total sum of failures or survivals, multiplied by the stress levels. B : the total sum of failures or survivals, multiplied by the square of the stress levels. * a negative sign was used when the analysis was based on failures.

C. Equation for the analysis of translucency parameter

TP = [(Lw – Lb)2 + (aw – ab)2 + (bw – bb)2]1/2

Where L refers to the lightness, a redness to greenness and b yellowness to blueness respectively coordinates in the CIE color space.

Appendix V: List of equations used in this study.