Zirconia surface modifications for implant dentistry

Accepted Manuscript Zirconia surface modifications for implant dentistry

Fernanda H. Schünemann, María E. Galárraga-Vinueza, Ricardo Magini, Márcio Fredel, Filipe Silva, Júlio C.M. Souza, Yu Zhang, Bruno Henriques PII: DOI: Reference:

S0928-4931(18)32000-9 https://doi.org/10.1016/j.msec.2019.01.062 MSC 9320

To appear in:

Materials Science & Engineering C

Received date: Revised date: Accepted date:

13 July 2018 13 January 2019 14 January 2019

Please cite this article as: Fernanda H. Schünemann, María E. Galárraga-Vinueza, Ricardo Magini, Márcio Fredel, Filipe Silva, Júlio C.M. Souza, Yu Zhang, Bruno Henriques , Zirconia surface modifications for implant dentistry. Msc (2018), https://doi.org/10.1016/ j.msec.2019.01.062

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Zirconia surface modifications for implant dentistry

Fernanda H. Schünemanna, María E. Galárraga-Vinuezaa, Ricardo Magini,a Márcio Fredelb, Filipe Silvac, Júlio C. M. Souzac,d, Yu Zhange, Bruno Henriquesb,c

University

PT

School of Dentistry (DODT), Post-Graduate Program in Dentistry (PPGO), Federal of Santa Catarina (UFSC), Campus Trindade, 88040-900, Florianópolis/SC,

RI

a

b

SC

Brazil

Ceramic and Composite Materials Research Group (CERMAT), Federal University of

CMEMS-UMinho, University of Minho, Campus de Azurém, 4800-058 Guimarães, Portugal

d

Department of Dental Sciences, University Institute of Health Sciences (IUCS), CESPU,

MA

c

NU

Santa Catarina (UFSC), Campus Trindade, Florianópolis/SC, Brazil

Gandra, Portugal e

D

Department of Biomaterials and Biomimetics, New York University College of Dentistry,

AC

CE

PT E

NYU, New York, NY 10010, USA

Correspondence to: Ceramic and Composite Materials Research Group (CERMAT), Federal University of Santa Catarina (UFSC), Campus Trindade, Florianópolis/SC, Brazil E-mail address: [email protected] (B. Henriques)

1

ACCEPTED MANUSCRIPT ABSTRACT Background: Zirconia has emerged as a versatile dental material due to its excellent aesthetic outcomes such as color and opacity, unique mechanical properties that can mimic the appearance of natural teeth and decrease peri-implant inflammatory reactions. Objective: The aim of this review was to critically explore the state of art of zirconia surface

PT

treatment to enhance its biological and osseointegration behavior in implant dentistry.

RI

Materials and Methods: An electronic search in PubMed database was carried out until May 2018 using the following combination of key words and MeSH terms without time

SC

periods: “zirconia surface treatment” or “zirconia surface modification” or “zirconia coating”

NU

and “osseointegration” or “biological properties” or “bioactivity” or “functionally graded properties”.

MA

Results: Previous studies have reported the influence of zirconia-based implant surface on the adhesion, proliferation, and differentiation of osteoblast and fibroblasts at the implant to

D

bone interface during the osseointegration process. A large number of physicochemical

PT E

methods have been used to change the implant surfaces to improve the early and late bone-toimplant integration, namely: acid etching, gritblasting, laser treatment, UV light, CVD, and

CE

PVD. The development of coatings composed of silica, magnesium, graphene, dopamine, and bioactive molecules has been assessed although the development of a functionally graded

AC

material for implants has shown encouraging mechanical and biological behavior. Conclusion: Modified zirconia surfaces clearly demonstrate faster osseointegration than that on untreated surfaces. However, there is no consensus regarding the surface treatment and consequent morphological aspects of the surfaces to enhance osseointegration.

KEY WORDS: zirconia, surface modification, implant surface, zirconia surface treatment, bioactivity, osseointegration, functionally graded materials

2

ACCEPTED MANUSCRIPT 1. INTRODUCTION In the last decade, yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) has emerged in dentistry as a promising material for various applications such as multi-unit, crowns, onlays, inlays, and implant structures, due to its aesthetic outcomes such as color and opacity that mimic a natural teeth appearance [1]. Zirconia-based materials have been claimed as a

PT

biomaterial with a high chemical stability that avoid the release of toxic products to the

RI

surrounding tissues [2,3]. Y-TZP provides stimulation of osteogenic cells during

SC

osseointegration in combination with unique mechanical characteristics such as high fracture toughness, fatigue resistance, high bending strength, high corrosion resistance, and

NU

radiopacity, as well as a higher affinity to bone tissue than most alternative biocompatible ceramics [4,5]. Additionally, some studies have shown that zirconia decrease bacteria

MA

adhesion and biofilm accumulation leading to low risk of inflammatory reactions in adjacent peri-implant tissues [6–8]. Moreover, recent in vitro and in vivo studies have demonstrated

D

that zirconia implants have similar results regarding osseointegration indexes when compared

PT E

to titanium implants [9–15]. Nevertheless, corrosion and the greyish color of titanium are both considered as disadvantage since that can affect health state and appearance of the peri-

CE

implant tissues, causing aesthetic drawbacks [16,17]. In implant dentistry, osseointegration is a biological dynamic process described as the direct

AC

contact of bone tissue to the implant surface that depends on factors related to the implant, surgical site, bone type, and patient conditions [9,18–20]. The bone to implant contact (BIC) can be measured by histomorphometric analyses at different time points over the period of osseointegation [10,19–22]. Previous studies have reported similar results for bone healing surrounding zirconia or titanium implants [6,13,15,23]. However, zirconia-based surfaces have revealed lower number of bacteria when compared to implant surfaces regarding microbiological assays [24,25]. Despite the favorable findings recorded for zirconia-based

3

ACCEPTED MANUSCRIPT surfaces, clinical long-term results are still lacking and some controversies towards zirconia osseointegration are still being debated. Some previous studies have reported high failure rates and zirconia peri-implant crestal bone loss in human studies [8]. Also, zirconia has been claimed as an inert biomaterial [2,3] although the adsorption of blood protein, platelets and migration of cells suggest a biological interaction with zirconia-based surfaces. That should

PT

be further studied considering chemical bonding and the deterioration of zirconia. Even

RI

though zirconia implants offer aesthetic benefits over titanium implants, titanium-based

SC

materials still possess higher mechanical strength over zirconia and it is currently the firstchoice material for dental implants. Nevertheless, implant technology has devoted significant

NU

efforts to modify zirconia regarding morphological and bioactive aspects that is desirable for an appropriate cell attachment, proliferation, and differentiation during the surrounding bone

MA

healing [3,26]. On improving zirconia surfaces, several physicochemical methods have been used such as: grit blasting [27], laser treatment [28], micro-machining, CVD, and PVD. The

D

development of coatings composed of silica, magnesium, graphene, dopamine, and bioactive

PT E

molecules has been assessed although the development of a functionally graded material for implants has shown an enhancement in mechanical behavior and biological response face

CE

[28].

Thus, the aim of this review was critically explore the state of the art of surface treatments to

AC

enhance the biological and osseointegration behavior of zirconia-based implants in dentistry.

2. SEARCH STRATEGY A literature review was performed on PUBMED database to identify relevant studies regarding zirconia surface treatment to enhance osseointegration. The electronic search was performed using the following combination of key words and MeSH terms: “zirconia surface treatment”

OR

“zirconia

surface

modification”

OR

“zirconia

coating”

AND

4

ACCEPTED MANUSCRIPT “osseointegration” OR “biological properties” OR “bioactivity” AND “mechanical properties” OR “functionally graded properties”. The inclusion criteria used for this review involved clinical trials, meta-analyses, in vivo, and in vitro studies written in English language up to May 2018. Three of the authors (BH, MEG, FHS) independently evaluated the titles and abstracts of potentially relevant previous studies. Selected studies were

PT

individually read and analyzed concerning the focus of the present review, which was to

RI

discuss and summarize important key publications regarding zirconia surface modifications

SC

for dental implants. Author names, journal, publication year, objectives, methods, and main

NU

outcomes were retrieved from the selected relevant articles.

3. RESULTS AND DISCUSSION

MA

Investigations have suggested that zirconia surface modification influences on osteoblast and fibroblasts adhesion, proliferation, morphology, and differentiation leading to the

D

osseointegration of implant surfaces and fit to the soft peri-implant tissue [29,30]. The

PT E

understanding of surface physicochemical

modifications

on biocompatibility and

osseointegration measured by histomorphometric analyses have been copiously evaluated to

CE

predict the clinical outcome and peri-implant tissue stability over time [31,32]. Accordingly, a large number of methods have been developed to change dental implants physicochemical

AC

properties to accelerate and improve the early and late bone-to-implant response [19] as shown in Figure 1 and Table 1.

5

SC

RI

PT

ACCEPTED MANUSCRIPT

NU

Figure 1. Schematics and SEM images on different zirconia surface modifications: machined

3.1. Machined zirconia implants

MA

[33], acid etched [34], grit blasted [33], ZLA [25], and multi-layered coatings [35–38].

D

Implant dentistry chronological records have reported the success and favorable histologic

PT E

outcomes of titanium machined dental implants over a period of 50 years [3]. As follows, machined zirconia implant have been studied showing promising results on the enhancement

CE

of osseointegration and an additional antibacterial activity. Scarano et al. examined BIC of machined zirconia implants fort 4 weeks and reported BIC values of around 68.4% without

AC

the presence of inflammatory or multinucleate cells claiming that machined zirconia implants can be highly biocompatible and osseointegrated [6]. Hafezeqoran et al. compared in a systematic the BIC percentage of machined zirconia and titanium dental implant from previous studies. Such previous review article reported statistically equivalent BIC% values for machined zirconia (33.74% - 84.17%) compared to machined titanium implants (31.8% 87.95%). Consequently, the study concluded that machined zirconia implants can be as osseointegrated as machined titanium implants [39]. The BIC percentage range of machined

6

ACCEPTED MANUSCRIPT zirconia implants analyzed in histological studies that range from can be seen in Table 1. The highest BIC percentage value corresponded to a study [40] which evaluated zirconia implants for 6 months while the lowest BIC values (32%) were related to evaluation for 4 weeks after surgery[41]. Thoma et al. (2015) showed that non-modified zirconia implants had a statistically similar BIC percentage and peri-implant soft tissue dimensions to acid etched-

PT

sandblasted titanium implants although zirconia implants exhibited a considerable fracture

RI

rate after 6 months of loading [40].

SC

Considering antibacterial response, Roehling et al. investigated multi-species biofilm adherence on zirconia machined (ZrO2-M) surface compared to titanium machined (Ti-M)

NU

surface. A statistically significant decrease in the biofilm thickness was noticed on zirconia-

MA

based surfaces when compared with titanium machined surfaces [25].

Table 1. BIC percentage and roughness values among machined surface, grit blasted surface,

BIC (%)

Weeks

Study

Treatment

(µm)

Rabbit

Machined

-

68.4 ±6 2.4

4

Rabbit

Machined

-

32.15 ±10.8

4

Rabbit

Machined

-

62.14 ±2.8

6

Rabbit

Machined

0.788

78.9

8

Rabbit

Machined

-

33.74 ±14.5

12

Scarano et al.

AC

Kim et al. 2017

Roughness

CE

Author

2003 [6]

Surface

PT E

In Vivo

D

acid etched surface, laser, and UV light modified zirconia surface after different time points.

[41]

Aboushelib et al. 2013 [42] Han et al. 2016 [18] Hoffmann et al.

7

ACCEPTED MANUSCRIPT 2012[43] Koch et al. 2010 Dog

Machined

-

59.11 ±7.5

4

Dog

Machined

0.85 + 0.04

57 ±15.2

20

Dog

Machined

-

Rabbit

Sandblasted

-

Minipig

Sandblasted

[44] Montero et al. 2015[45]

PT

Thoma et al.

87.7 ±25.1

Hoffmann et al.

2010 [46]

0.98

54.6 ±17.6

13

1.162

57.6 ±23.7

13

-

67.4 ±17

36

Sandblasted and

MA

Schliephake et al.

12

NU

Schliephake et al.

24

41.350 ±15.8

SC

2012 [43]

RI

2015 [40]

Minipig

Acid etched

Kohal et al. 2004 Monkey

Sandblasted

PT E

[13]

D

2010 [46]

Sheep

Sandblasted

1.67 + 0.08

75.1 ± 4.2

12

CE

Bacchelli et al.

Pig

Acid Etched

0.63 + 0.05

63 ±21.5

12

Minipigs

Acid Etched

0.598

71.4 ±17.8

12

-

86.24 ±9.7

8

2009 [27] Gahlert et al. 2012

AC

[10]

Depprich et al. 2008 [9]

Liñares et al. 2016

Sandblasted and Minipigs

[47]

Acid Etched

Janner et al. 2018

Sandblasted and Dog

[48]

71.15 ±7 -

16

Acid Etched

8

ACCEPTED MANUSCRIPT

Sand Blasted

66.75

Kubasiewicz-Ross Minipigs

Acid Etched

-

72.9

8

et al. 2018 [11] Sand Blasted &

68.8

Etched

47.9

12

SC

Dogs

Laser modified

PT

Cavo-Guirado JL -

-

60.34 ±4.3

8

Laser Modified

2.83 + 0.2

48 ±3

(femtosecond

9.6 + 0.62

78 ±5

Laser Modified

-

65 ± 4.4

12

Laser Modified

-

43.87 ±14.5

12

0.12 ± 0.02

52.7

RI

et al. 2015 [49] Laser modified Delgado-Ruiz et Dogs

(femtosecond

al. 2015 [50]

NU

laser)

Delgado-Ruiz et

MA

Sandblasted

Dogs al. 2014 [51]

8

D

laser)

PT E

Cavo-Guirado et

Dogs al. 2014 [52]

CE

Hoffmann et al.

Rabbit

AC

2012 [43]

UV light (15 min) machined

Brezavscek et al.

Rat

4

2016[53] UV light (15 0.21 ± 0.08

86.5

min) rough *(-) absent data in the study

9

ACCEPTED MANUSCRIPT 3.2. Grit blasted and acid etched zirconia surface treatment Previous studies have reported that airborne particle abrasion known as grit blasted surface treatment followed by acid-etching (SLA treatment) to increase the surface area of zirconia implants for osseointegration [13,54,55] (Table 1). The grit blasting process with 50-110µm Al2O3 particles, has been shown as an alternative to increase the surface area for osteoblasts

PT

attachment and then to speed up the osseointegration process. For Gahlert et al. (2007) [33]

RI

and Bacchelli et al. (2009), grit blasting zirconia implant surfaces significantly improved the

SC

peri-implant osteogenesis and osseintegration when compared to machined titanium surfaces [10,27]. Gahlert et al. (2007) recorded the removal torque on 64 implants, including zirconia

NU

grit blasted with Al2O3 particles, machined zirconia, and grit blasted titanium (with 0.2-0.5 µm Al2O3) structures. The results showed significantly higher removal torque values for grit

zirconia (25.9 N/cm) surfaces [33].

MA

blasted zirconia (40.5 N/cm) and titanium (105.2 N/cm) than those recorded on machined

D

Other studies have shown different results, Kohal et al (2004) investigated the

PT E

osseointegration on unloaded zirconia implants compared to titanium implants five months after tooth extraction. The titanium implant surfaces were grit blasted with Al2O3 and acid

CE

etched (H2O2/HF) while zirconia implants were only grit blasted with 50 μm Al2O3/50μm. The results showed that the mean height of the soft peri-implant tissue cuff was 5 mm around

AC

the titanium implants and 4.5 mm around the zirconia implants. The BIC was around 72.9% on titanium implants and 67.4% on zirconia implants. With these results, the mentioned study concluded that grit blasted zirconia implants revealed similar integration to bone and periimplant soft tissue dimensions when compared to SLA titanium implants [13]. Moreover, grit blasting has been performed with additional chemical treatments such as: hypo-phosphorous acid, mixture of KOH, and NaOH to improve BIC of zirconia. Though, hydrofluoric acid (HF) etching appears to be the first choice to enhance bone apposition

10

ACCEPTED MANUSCRIPT resulting in higher implant removal torque values [34,56]. The incorporation of fluoride at the ceramic surface could enhance osteoblastic differentiation and interfacial bone formation, as found for fluoridated titanium surfaces [57–59]. A commercially zirconia implant treated with HF etching showed BIC at 81% [60]. Besides, other studies have reported the effect of acid etching treatment on zirconia surfaces

PT

and its impact on biofilm adhesion. Depprich et al. (2008) compared the BIC percentage for

RI

24 Y-TZP acid-etched implants (Ra=0.598µm) with 24 acid etched titanium implants

SC

(Ra=1.77µm). The peri-implant tissues were histologically inspected after 1, 2, and 4 weeks. A significant BIC increase was observed on acid etched zirconia implants compared to

NU

titanium implants [9]. Also, when Roehling et al. (2017) reported a decrease in biofilm growth on grit blasted and acid etched zirconia surface (ZrO2-ZLA) when compared with

MA

titanium grit blasted titanium surface (Ti-SLA) [25].

In another study, zirconia disks were acid etched in 5%, 20% and 40% HF for 30 min, 1h and

D

2h (Flamant et al., 2016). The concentration and time that had the most uniform and faster

PT E

roughening were 40% and 60 min, but no strength or fatigue tests were performed. In this study, the etching at 40% HF dissolved zirconium and yttrium oxide producing fluoride, and

CE

hydroxide complexes. Yttrium oxides have very low solubility in 40% HF leading to the precipitation of yttrium trifluoride octahedral crystals on the surface. Yet, zirconium oxides

AC

are partially soluble an bonded to yttrium, zirconium and fluoride precipitates, probably because the saturation threshold for zirconium fluoride complexes [34]. Oh et al. (2017) tested HF in two different concentrations (10% and 20%) and in different time points (1, 2, 10, and 60 min) in pure zirconia, porcelain, and in bioactive glass that was infiltrated into pre-sintered zirconia. The roughness of zirconia was not affected by the etching time or the concentration of the acid although etched bioactive glass-infiltrated zirconia revealed similar surface topographic aspect when compared to grit blasted/acid-etched titanium [61].

11

ACCEPTED MANUSCRIPT Hempel et al. (2010) cultured osteoblasts SAOS-2 cells on grit blasted, grit blasted/etched zirconia and compared with grit blasted/etched titanium. The findings showed an increase in adhesion, spreading, and differentiation of SAOS-2 cells when compared with titanium. However, there was no significant differences between zirconia surface treatments [62]. Additionally, Bergenmann et al. compared the human primary osteoblasts osteogenic marker

PT

gene modulation on different zirconia surfaces: machined, grit blasted, acid etched/grit

RI

blasted and acid etched/sandblasted/heated with machined titanium implants. The present

SC

study showed that both acid etched surfaces with Ra roughness values of around 1.3 µm had a drastically increase of osteocalcin expression and cell adherence when compared with

NU

machined titanium (Ra: 0.54 µm) and machined zirconia (Ra at 0.59 µm). In fact, higher roughness values corresponded to acid etched surfaces with a more favorable area for

MA

osteoblasts adhesion [63]. The roughness values recorded in the previous studies corresponded to the moderate rough titanium implants that has been claimed to promote high

D

BIC percentage and successful osseointegration in previous in vivo studies[64].

PT E

An in vivo study reported the BIC percentage around zirconia implants after surface conditioning in different solutions. HF acid etching and immersion in NaOH and KOH was

CE

compared regarding the enhancement of osseointegration and therefore the BIC percentage was higher for the etched surfaces in HF. Those surface treatments induced the proliferation

AC

of multinucleated giant cells around the implant surfaces [65]. Liñares et al (2016) compared nine different zirconia or titanium implants considering the following surface treatment to bone integration in minipig mandibles: grit blasting with large grits of 250-500 m and acid etched with HCl/ H2SO4. BIC percentage of the titanium implants was around 84% while zirconia revealed a BIC around 86.2%. Additionally, gingival tissue around zirconia implants presented higher organization of collagen fibers and lower sulcus depth measurements than

12

ACCEPTED MANUSCRIPT that inspected around titanium. That suggested a more mature and organized peri-implant soft tissue around zirconia implant surfaces [47]. Even though the described surface treatments have provided surface topographic and biological advantages, the mechanical properties of treated zirconia can change affecting the clinical long performance of the implant. The strength and phase transformation of grit

PT

blasted zirconia has been questioned by previous studies [54,66,67]. Grit blasting can induce

RI

stress concentration and consequently a transition from tetragonal to monoclinic phase. Thus,

SC

this phase transition can improve zirconia mechanical properties due to the introduction of compressive stress, but can also cause degradation of zirconia affecting its density and

NU

mechanical stability [54,68]. A systematic review reported that the flexural stress of grit blasted yttria-stabilized zirconia increased, regardless abrasion factors and aging effect [67].

MA

Studies have also reported that grit blasting decrease the fatigue resistance of zirconia [66]. A study showed that grit blasting zirconia with 105 μm alumina, HF acid etching, and 1h of

D

heat treatment is a reliable process to increase zirconia roughness to 1.2 μm which is

PT E

comparable to the standard titanium roughness (1.5 μm) that can support a successful osseointegration rate [64]. That study showed an increase if the zirconia flexural strength

CE

after grit blasting, nevertheless the fatigue strength was not assessed [54,64]. As a matter of fact, the strength of zirconia might be reduced by particle abrasion, since that can cause deep

AC

micro-cracks. At first, any compression caused by particle abrasion can strengthen and inhibit micro-crack extension due to zirconia phase transformation supporting the results from previous studies on the benefits of grit blasting [54,67]. Nevertheless, Zhang et al. have shown in their study that the compressive stresses caused by grit blasting are not enough to counteract the strength loss caused by micro-cracks specially under high static load and fatigue tests which resemble real clinical conditions [66]. Clinically, zirconia implants should be grit blasted with soft and round particles, avoiding the use of sharp particles to decrease

13

ACCEPTED MANUSCRIPT the formation of micro-cracks. More studies involving fatigue tests are needed to evaluate which grit blasting parameters are proper to attain a desired roughness and to decrease microcrack formation [54,66]. Other studies have also revealed that heat and acid treatment can decrease zirconia flexural strength due to tetragonal to monoclinic phase transformation and low temperature

PT

degradation conditions[69,70]. In a recent study, Xie et al. evaluated the effects of three types

RI

of acid treatments on zirconia. Hydrofluoric (HF), acetic, and citric acid were tested at

SC

different concentrations. HF acid was the most efficient to increase roughness, however, 40%HF treatment at room temperature decreased considerably the surface hardness and

NU

flexural strength of the samples. As follows this study concluded that the acid concentration should be maximum 5% to avoid any potential damage to zirconia mechanical structure [55].

MA

Fischer et al. showed that after 4 h of HF etching, zirconia strength decreased after 4h HF etching while 1h etching was recommended although a short time of etching could not

D

improve the morphological aspects of zirconia implants [54]. Even though acid etched

PT E

zirconia has been claimed as a promising material that enhances osseointegration, further studies are needed to determine which etching conditions would not affect the mechanical

CE

behavior of zirconia.

AC

3.3 Ultraviolet light treated zirconia Regarding in vitro and in vivo studies, UV light treatment has been claimed to be an effective zirconia surface treatment to enhance the attachment, proliferation, and differentiation of osteoblast without affecting zirconia mechanical properties [53,71]. UV light can induce electron excitation, increasing zirconia surface energy. Henningsen et al. reported an increase in wettability of zirconia surfaces treated by UV light to an ultra-hydrophilic state. The water contact angle of grit blasted zirconia surfaces decrease from 51° down to 9.4° after UV light

14

ACCEPTED MANUSCRIPT treatment, as seen in Table 2 [71]. The fact that UV treatment increases zirconia wettability was also supported by another previous study testing only 15 min UV light [56]. Additionally, histomorphometric analysis revealed that UV treated zirconia specimens had a faster osseointegration process and higher BIC percentage (86.5%) when compared to untreated zirconia after 2 and 4 weeks of implantation. After 4 weeks, untreated samples had

PT

still fibrous connective tissue at the implant-bone interface while UV treated samples were

RI

almost entirely surrounded by bone (Table 1). Another study showed that UV treated zirconia

SC

became super-hydrophilic and increase human alveolar bone-derived osteoblasts attachment and spreading after 21 days when compared to untreated samples concluding that UV

NU

treatment can induce faster healing and higher BIC percentage [72]. Even though, some studies have suggested that UV surface treatment is a promising strategy to promote bone

MA

morphogenesis around zirconia implants, additional in vivo studies are needed to validate this

PT E

3.4 Zirconia laser modification

D

concept [53,71,73].

Laser treatment is a promising alternative to modify and enhance zirconia osseointegration

CE

[71,73–76]. Hoa et al. used a CO2 laser to modify Y-TZP surfaces and possibly achieve a higher osseointegration index. The defocused CO2 laser beam was traversed in single time

AC

across the Y-TZP surface at different intensities, namely 1.80 and 2.25 kW/cm2. The CO2 laser treatment decrease the roughness of the samples from 0.35 µm down to 0.2 µm although that increased the surface energy and consequent wettability [77]. Moura et al. investigated the influence of surface texturing on Y-TZP by using laser treatment compared to different surface treatments: as sintered sample (AS), grit blasting and acid etching treatment (SE), laser irradiation using two output power of 0.9 W (LI) and 1.8 W (LII). The surface was analyzed by SEM/EDS analyses, water contact angle, friction test by

15

ACCEPTED MANUSCRIPT bone plates and by roughness analysis. The water angle contact of laser treated Y-TZP was 36.4° (LI) and 38.2° (LII) while the AS and SE groups presented higher water contact angle values (46.9° ± 5° for AS and 44.6° ± 3° for SE) that showed a lower hydrophilicity. In fact other in vitro studies have shown that CO2 laser modified zirconia increases osteoblast (hFOB) adherence when compared to untreated samples [77]. It is important to take in

PT

consideration that material water contact angles lower than 90° are considered hydrophilic,

RI

and less than 20° are super-hydrophilic. As follows, lower contact angles mean the material

SC

has a higher wettability, which is biologically a more attractive surface for osteoblast proliferation, protein adsorption, and osseointegration [78]. The contact angle and wettability

NU

measured in several studies for different types of zirconia surface treatments are shown in Table 1.

MA

Furthermore, laser treatment has been applied to create micro-grooved surfaces in zirconia implants. The microtexture could change collagen fiber organization, peri-implant bone

D

architecture, and human cell metabolism. Studies have shown that surfaces with a regular

PT E

geometry in the micro-range can increase osteoblast proliferation, adhesion, spreading and matrix protein synthesis [49,50]. Delgado-Ruiz et al. treated zirconia through femtosecond

CE

laser to create a uniform micro-grooved surface with symmetric microstructures. An animal study showed that laser treated microogroved zirconia implants had a high number of

AC

transverse collagen fibers and an increased bone remodeling when compared to grit blasted zirconia implants which had parallel collagen fibers and SLA titanium implants which had parallel and transverse fibers but low bone remodeling rates. The difference among bone remodeling rates after 4 months of loading could be explained by the presence of blood vessels and bone cells that penetrated in micro-grooved zirconia surfaces which accelerated the osseointegration rate. Also the presence of transverse collagen fibers create a favorable stress distribution environment in loaded implants favoring bone metabolism[50]. Laser

16

ACCEPTED MANUSCRIPT treated microgrooved zirconia implants show promising results, however further studies involving humans are required to validate that.

Table 1 – Water Contact angle and wettability measured in several studies for different types of zirconia surface treatments Materials

Treatment

Contact

Wettability

angle Polished titanium

74.32 + 1.34°

Titanium blasted with zirconia

131.51 +

with zirconia/acid

1.50°

etched ZrO2-TZP-A-

Polished

HIP

82.79 +

(Y, Nb)-TZP

PT E

and

Zirconia powders with particle size ≤44 μm; 4.5 bar; 3 cm distance

Hydrophobic

acid etching: 0.2 wt.% hydrofluoric acid for 1.5 min Hydrophilic

Hydrophilic Sandblasting: 50 μm Al2O3 at 2 bar and 1

HA-coated 2015 [80]

Sandblasting:

Hydrophilic

2.10°

D

Y, Cho.

NU

Titanium blasted

MA

Titanium

87.3 + 5.00°

SC

2012 [79]

Hydrophilic

RI

Al-Radha,

Observations

PT

Author

63.72 ±

surfaces (after

(Y, Ta)-YZP

bar 2.55°

sandblasting)

CE

Non-coated

HA Film by Aerosol Deposition: ~10 μm 95.0 ± 3.21°

Hydrophobic

zirconia surfaces

Liu, M. 2015 [32]

AC

(sandblasted)

Y-ZrO2

Polished +

Hydrophilic

Zirconia: Zenostar, Wieland Dental,

Polydopamine

German 64 ± 1°

coating

dopamine solution: (2 mg/mL in 10 mM

(Zenostar)

Tris-HCl, pH 8.5) and gently shaken for Uncoated

24 h at room temperature

Hydrophilic 78 ± 4°

(Polished) Yang Y.

Y-ZrO2

Polished + UV

2015 [75]

(Zenostar)

light treatment

33.76°

Hydrophilic

Zirconia: Zenostar, Wieland Dental, German

17

ACCEPTED MANUSCRIPT Polished

51.98°

Hydrophilic

UV light; 24 h;

Sandblasted + UV

36.15°

Hydrophilic

10-W bactericidal lamp; 17 mW/cm2 Sandblasting: (Al2O3) particles (25 μm)

light treatment 63.87°

Hydrophilic

MPa

Sandblasted Moura, CG.

3Y-TZP

from a distance of about 20 mm at 0.2

As sintered

46.9 ± 5°

Hydrophilic

Sandblasting and

44.6 ± 3°

Hydrophilic

PT

2017 [28] Sandbasting: Al2O3; 100 μm particles; 6

38.2 ± 1°

NU

(0.9W)

Laser irradiation

36.4 ± 1°

Titanium

Sandblasted +

A, 2018 [71]

grade IV

acid etched

30 min; Laser: Nd: YAG laser

Hydrophilic

111°

Hydrophobic

12.8°

Super-Hydrophilic

Sandblasting: ZrO2 particles

0

Super-Hydrophilic

λ =250nm (2 mW cm-2)

Ar-Plasma

0

Super-Hydrophilic

Non-thermal plasma of either Argon and

Zirconium dioxide

51°

Hydrophilic

CE

O2-Plasma

AC

5Y-TZP

Etching: hydrofluoridine acid (48%) for

PT E

UV

D

Henningsen

MA

(1.8W)

bar; 10 mm distance

Hydrophilic

SC

Laser irradiation

RI

etching treatment

UV light at λ=360nm (0.05mWcm-2) and

oxygen using a non-thermal plasma reactor

blasted UV

9.4°

Super-Hydrophilic

O2-Plasma

4.2°

Super-Hydrophilic

Ar-Plasma

2.9°

Super-Hydrophilic

3.5. Coatings on zirconia Implant dentistry innovations face the primordial challenge of enhancing biological and mechanical implant properties through approaches like implant coating. Different coatings on zirconia surfaces have been developed to enhance biocompatibility, antibacterial potential,

18

ACCEPTED MANUSCRIPT and bioactivity. Bioactive coatings on zirconia have demonstrated advantages for bioactivity, since they have the ability to induce hydroxyapatite formation in a biological environment, which is essential for subsequent bone proliferation. In literature, different coating materials with favorable biologic properties have been described, such as: silica, magnesium, nitrogen,

AC

CE

PT E

D

MA

NU

SC

RI

PT

carbon, calcium phosphate, hydroxyapatite, dopamine, and graphene [26,37,61,81–85].

Figure 2. Zirconia coatings showing biological advantages in terms of bioactivity, osseointegration, and antibacterial effects

Laranjeira et al. compared the in vitro behavior of fibroblast adherence and antibacterial effect on different types of silica-coated micropatterned zirconia surfaces. The study results showed that silica coated zirconia samples with different surface morphological aspects reduced bacterial adhesion. Microstructured bioactive coating can also be an efficient strategy

19

ACCEPTED MANUSCRIPT for fibrin network formation, cell growth, and improved soft tissue adherence since it reduces biofilm adherence and enhances the adsorption of proteins and cell migration [35]. Additionally, Kirsten et al. analyzed a novel glass composition (PC-XG3) zirconia coating and its in vitro bioactivity using the simulated body fluid (SBF) immersion test. Smooth and microstructured glass coatings were applied on zirconia implants, which showed a strong

PT

adhesion to the zirconia substrate and a significant increased in vitro bioactive behavior after

RI

SBF immersion [86]. Consequently, silica coatings can increase the zirconia bioactivity

SC

promoting hydroxyapatite formation when in contact with body fluids which will stimulate

Magnesium, nitrogen, and carbon coatings

NU

osteoblast proliferation on the implant surface[87], accelerating osseointegration.

MA

Studies have reported that magnesium (Mg) coatings favor osteoblast proliferation, increasing the zirconia bioactivity [88]. Pardun et al. [26] reported the influence of Mg

PT E

D

addition to zirconia-calcium phosphate and found that Mg containing coatings promoted a higher cell proliferation and differentiation in comparison to pure zirconia-calcium phosphate coatings. Microstructure tests confirmed a porous and a stable coating adhesion not hampered

CE

by its composition. Other studies have shown that magnesium-calcium coatings increase the

AC

bioactive potential of zirconia. That showed a multilayered hydroxyapatite (HA) precipitate revealing a "cauliflower" morphology after 7 days of SBF immersion[36,89]. Moreover, the addition of other elements like nitrogen and carbon have improved the biological and mechanical properties of zirconia [90]. Another study showed a high hydrophilicity, bioactivity, and antibacterial potential for zirconia containing a nitrogen-doped hydrogenated amorphous carbon (a-C:H:N) layer. Schienle et al. tested the bacterial adherence to 3Y-TZP with a carbon (a- C:H:N) coating and quantified the adherent microorganisms by estimating the colony-forming unit analysis (CFUs). The a-C:H:N coated Y-TZP surfaces revealed a low

20

ACCEPTED MANUSCRIPT adhesion of bacteria on the surface compared to uncoated surfaces [83]. Other studies have also coated zirconia with functionalized multiwalled carbon nano-tubes increasing the roughness, wettability, and cell adhesion of this material favoring zirconia´s osseintegration properties [90,91].

PT

Hydroxyapatite and calcium phosphate based coatings

RI

Hydroxyapatite (HA) has a similar mineral composition to that of bone, and thus shows

SC

bioactive properties favoring tissue response that enhances osseointegration. HA has been used to coat zirconia in order to convert highly stable implant surface into a bioactive one,

NU

thus enhancing its osseointegration features. Porous zirconia scaffolds coated with HA have been used as a drug delivery vehicle to enhance bone response and assure good

MA

osseointegration [80,92,93]. Aboushelib and Shawky evaluated the osteogenesis ability of CAD/CAM porous zirconia scaffolds enriched with HA. Results revealed a significantly

PT E

D

higher volume of new bone formation (33 ±14%) on HA enriched zirconia scaffolds compared to the scaffolds free of HA (21 ±11%), therefore, demonstrating the HA coating enhanced osteogenesis ability of porous zirconia scaffolds [94]. Pardun et al.

obtained

CE

coatings by mixing Y-TZP and HA in various ratios. The experiments revealed that the HA

AC

dissolution stimulated the adhesion and proliferation of osteoblasts. However, an increasing content of calcium phosphate resulted in a decrease of its mechanical and chemical stability, while the bioactivity increased after immersion in simulated body fluid. As follows, the author demonstrated excellent interfacial bonding, mechanical strength, and the bioactivity potential of coatings with higher tetragonal zirconia contents [84]. Calcium phosphate (CP) is also considered bioactive and thus stimulate bone regeneration due to their chemical composition close to that of the mineral phase of bone commonly named biological apatite. However, pure calcium phosphate coatings exhibit a poor stability

21

ACCEPTED MANUSCRIPT and provide a weak bonding strength to the substrate. To overcome these drawbacks of pure CP coatings, studies used tricalcium phosphate reinforced hydroxyapatite (HA/TCP) coatings over zirconia surfaces, with open pores larger than 100 μm, a bonding strength of 24 MPa showing a high interfacial bonding between coating and substrate. Additionally, those

PT

coatings exhibited bioresorbable and osteoconductive properties [95,96].

RI

Dopamine

SC

Dopamine, precursor of 3,4-dihydroxy-L-phenylalanine (L-DOPA), was found to be an important component in the adhesive structure of mussels as it can self-cure and adhere

NU

strongly to a wide range of organic and inorganic materials [97]. Polydopamine (PDA) coatings can enhance antimicrobial properties and facilitate the protein adsorption and cell

MA

adhesion, accelerating biological processes such as osseointegration [98]. The influence of novel PDA coating on zirconia disks regarding soft-tissue integration and antibacterial effect

PT E

D

was explored by a previous study [38]. Such study evaluated modified surface zirconia with PDA. The surface topography of zirconia coated with PDA can be seen by atomic force microscopy (AFM) and SEM inspection as shown in Figure 1 and 2. The polydopamine

CE

coating decreased significantly the bacterial activity and enhanced fibroblasts adherence,

AC

which has an important role in peri-implant soft-tissue integration. Therefore, that surface modification approach holds great potential for improving soft-tissue integration around zirconia abutments, which is another important clinical application in implant dentistry. Additionally, another study reported the coating of zirconia with L-DOPA which was a dopamine-derived residue secreted by marine mussels to promote zirconia biocompatibility and osteogenic response. The preliminary results of this study showed that L-DOPA coated specimens had a higher osteoblast proliferation and spreading when compared to uncoated specimens [99].

22

ACCEPTED MANUSCRIPT Graphene coatings Graphene has been the precursor of a novel multifunctional material that can act as a biocompatible surface coating to improve implant tribological properties and reduce wear [100–102]. Li et al. [37] prepared zirconia/graphene (ZrO2/GNs) composite coatings with a thickness of 5 – 20 nm using an atmospheric plasma spray system. It was noticed that the

PT

wear behavior rate of ZrO2/GNs reduced to 1.17×10−6 mm3/N m on 100 N normal loading,

RI

which resembled to a 50% decrease compared with the control group (ZrO2 specimens).

SC

Moreover, the results indicated that the ZrO2/GNs composite coating exhibited excellent wear resistance and low friction coefficient with the addition of GNs. A GNs-rich transfer layer

NU

protected the ZrO2/GNs composite coatings from severe wear by brittle microfracture, which significantly improved its tribological behavior [37]. Further studies should consider

MA

graphene to improve zirconia mechanical performance mainly regarding wear resistance in

D

implant dentistry.

PT E

2.5 Bioactive graded zirconia-based structures As previously referred, zirconia-based materials have a high elastic modulus, high chemical

CE

stability in human body, and desirable optical properties for esthetic outcomes. Nevertheless, the high elastic modulus results in stress shielding of the hard tissue, leading to local bone

AC

resorption. Bioactive ceramics (e.g. calcium phosphate ceramics, bioactive glasses) are reactive to the surrounding medium and stablish chemical bonds with adjacent tissues[103]. Also, those bioactive materials exhibit comparable modulus to hard tissues (bone, enamel, or dentin), which mitigates the stress shielding problems. Unfortunately, bioactive ceramics are relatively weak and thus structurally unstable, which hinders their use in load bearing applications (e.g. dental and orthopedic implants)[104].

23

ACCEPTED MANUSCRIPT Attempts have been made to produce bioactive glass coatings on zirconia substrates but with limited success. These coatings often undergo delamination and fracture caused by the coating/substrate bonding issue, mismatch in coefficient of thermal expansion (CTE), and the abrupt changes in physical properties at the coating/substrate interface. To overcome such issues, Zhang et al [105,106] proposed a bio-inspired strategy regarding transition in

PT

chemical composition and properties, as seen in Figure 6 [107–109]. That strategy relies on a

RI

functionally graded calcium phosphate-based glass/zirconia (CPG/Y-TZP) system with a low

SC

elastic modulus and a flexural strength similar to, or even higher than that recorded for YTZP [4,110,111].

NU

The osteoconductive CPG coating can speed up the osteointegration process and prevents micromotion at the implant/tissue interface [4,105,112] In addition, the residual outer surface

MA

CPG layer acts as an encapsulation layer, preventing hydrothermal degradation of the Y-TZP interior, and can be further transformed to a carbonate apatite (CHA) layer by immersing in

D

mineral precipitate solution or simulated body fluid (SBF) since the newly formed bone is

PT E

directly attached to a CHA layer. Despite the aforementioned advantages of this system, there is only a few studies on CPG/Y-TZP, contrasting to a vast literature on glass infiltrated

AC

CE

zirconia structures [4,104,107–114].

24

D

MA

NU

SC

RI

PT

ACCEPTED MANUSCRIPT

PT E

Figure 6: Optical micrographs of graded CPG/Y-TZP (a) rod (2 mm in radius) and (b) plate (1.2 mm thick) sections consisting of (c) CPG infiltrated Y-TZP (SEM image); (d) Energy

CE

dispersive X-ray line mapping from surface to interior, revealing a gradual transition in Ca and Zr contents. Higher magnification SEM images, insets of (c), showing: gradual transition

AC

from the surface residual CPG layer (left) to the graded CPG/Y-TZP structure (center) and to dense Y-TZP interior (right), modified from Zhang et al. US8703294 B2 – Bioactive graded zirconia-based structures, 2014.

4. CONCLUSIONS The current challenge in implant dentistry is to develop a surface treatment or zirconia-based structure that can have bioactive, mechanical, and osteogenic properties guarantying favorable early and long time clinical results. The present review analyzed and explored the

25

ACCEPTED MANUSCRIPT techniques currently reported for zirconia surface treatment and concludes important key points depicting desirable osseointegration, mechanical, and antibacterial properties as follow: 

Osseointegration depends on time and bone quality, heterogeneous in vivo studies involving different animal models, healing and loading periods, and diferent surgical sites limit an objective comparison among bone to implant contact results. Standard

PT

guidelines in methods, materials and surfaces are recommended to compare results 

RI

among scientific studies;

Machined zirconia implants have shown an adequate osseointegration when compared

SC

to machined titanium implants, however, treated zirconia implants have shown higher

NU

bone to implant contact indexes. An increase in roughness and improvement of surface morphological aspects can speed up the osseointegration process for both

No surface treatment has been claimed as first choice to increase zirconia

D

osseointegration potential, however surface modifications that increase roughness,

PT E

wettability, and surface energy in which osteoblasts can proliferate, adhere and spread are recommended to accelerate this dynamic process. Bioactive based graded

CE

structures and coatings are recommended to increase zirconia´s bioactivity and osseointegration. 

Grit blasting, acid etching, and heat treatment on zirconia should not decrease its

AC



MA

zirconia or titanium implants;

mechanical properties such as flexural strength and fracture load. Smooth and round particles for grit blasting are recommended to avoid micro-crack formation. 

Studies have shown that high acid concentrations, over etching time and heat is not recommended since it can increase the degradation of zirconia;



Functionally bioactive graded zirconia can improve the mechanical strength (e.g., flexural strength and fracture toughness) and biological properties of zirconia.

26

ACCEPTED MANUSCRIPT Bioactive materials added on the surface can improve osseointegration and decrease biofilm accumulation; 

In vitro and in vivo studies have shown that machined and acid etched zirconia decrease the adhesion of bacterial when compared to titanium. The low affinity of zirconia to biofilm and a favorable soft tissue adaptation is an essential aspect

PT

since it could reduce peri-implantitis rates which is the major current issue and

Modified zirconia-based surfaces should be evaluated in clinical studies to provide

SC



RI

cause of failure of titanium implant dentistry;

realistic point view of how oral biofilms, loading, and other patient conditions

NU

may affect the properties of zirconia. To date most studies are in vitro or animal

MA

studies, which do not provide realistic results.

5. OUTLOOK AND FUTURE PERSPECTIVES

D

Bioengineering advances have modified zirconia implant surfaces in various ways to improve

PT E

and accelerate bone healing response and clinically decrease the patient´s edentulous period. Moreover, zirconia has been coated with bioactive particles and multifunctional molecules

CE

which can induce an osteogenic stimulus, fibroblast adherence, and an additional antibacterial effect. In this way, zirconia can change from a “criticized bioinert” surface to a “bioactive”

AC

and multifunctional one pursuing the most favorable biologic and mechanical peri-implant tissue responses. Current studies show that zirconia can be converted into a bioactive system embedding diverse biomolecules that can mimic in a more realistic way bone tissue structure in a macro- and micro molecular level being able to induce various cell responses that favor implant treatment outcome. However, mechanical failure and crestal bone loss occurring around zirconia implants due to technical and biological complications converts the indication of zirconia as “first choice” implant material in a controversial issue [40,115,116].

27

ACCEPTED MANUSCRIPT Still, future in vitro, in vivo, and long term clinical studies are needed to evaluate success rates of treated zirconia implants in function. These studies should evaluate zirconia implants over time in terms of peri-implant bone stability, absence of inflammation, infection, mobility, and mechanical complications which will give a clearer panorama of which zirconia

PT

surface should be indicated.

RI

ACKNOWLEDGEMENTS

SC

This study was supported by FCT-Portugal (UID/EEA/04436/2013, NORTE-01-0145FEDER-000018 – HAMaBICo, FCT/02/SAICT/2017/3103-LaserMULTICER), CNPq-Brazil

NU

(PVE/CAPES/CNPq/407035/2013-3; CNPq/421229/2018-7) and by the United States National Institutes of Health, National Institute of Dental and Craniofacial Research (grant

PT E

D

MA

numbers R01DE017925, R01DE026772, and R01DE026279).

REFERENCES

B. Stadlinger, M. Hennig, U. Eckelt, E. Kuhlisch, R. Mai, Comparison of zirconia and titanium

CE

[1]

implants after a short healing period. A pilot study in minipigs, Int. J. Oral Maxillofac. Surg.

[2]

AC

39 (2010) 585–592. doi:10.1016/j.ijom.2010.01.015. C. Piconi, G. Maccauro, Zirconia as a ceramic biomaterial, Biomaterials. 20 (1999) 1–25. doi:10.1016/S0142-9612(98)00010-6. [3]

L. Yin, Y. Nakanishi, A. Alao, X. Song, A review of engineered zirconia surfaces in biomedical applications, Procedia CIRP. 65 (2017) 284–290. doi:10.1016/j.procir.2017.04.057.

[4]

Y. Zhang, Overview: Damage resistance of graded ceramic restorative materials., J. Eur.

28

ACCEPTED MANUSCRIPT Ceram. Soc. 32 (2012) 2623–2632. doi:10.1016/j.jeurceramsoc.2012.02.020. [5]

A. Della Bona, O.E. Pecho, R. Alessandretti, Zirconia as a Dental Biomaterial, Materials (Basel). 8 (2015) 4978–4991. doi:10.3390/ma8084978.

[6]

A. Scarano, F. Di Carlo, M. Quaranta, A. Piattelli, Bone Response to Zirconia Ceramic

doi:10.1563/1548-1336(2003)029<0008:BRTZCI>2.3.CO;2.

F. Rupp, L. Liang, J. Geis-Gerstorfer, L. Scheideler, F. Hüttig, Surface characteristics of dental

RI

[7]

PT

Implants: An Experimental Study in Rabbits, J. Oral Implantol. 29 (2003) 8–12.

[8]

SC

implants: A review, Dent. Mater. 34 (2018) 40–57. doi:10.1016/j.dental.2017.09.007. R.J. Kohal, F.S. Schwindling, M. Bächle, B.C. Spies, Peri-implant bone response to retrieved

NU

human zirconia oral implants after a 4-year loading period: A histologic and histomorphometric evaluation of 22 cases, J. Biomed. Mater. Res. - Part B Appl. Biomater.

[9]

MA

104 (2016) 1622–1631. doi:10.1002/jbm.b.33512.

R. Depprich, H. Zipprich, M. Ommerborn, C. Naujoks, H.-P. Wiesmann, S.

PT E

D

Kiattavorncharoen, H.-C. Lauer, U. Meyer, N.R. Kübler, J. Handschel, Osseointegration of zirconia implants compared with titanium: an in vivo study, Head Face Med. 4 (2008). doi:10.1186/1746-160X-4-30.

M. Gahlert, S. Roehling, C.M. Sprecher, H. Kniha, S. Milz, K. Bormann, In vivo performance

CE

[10]

AC

of zirconia and titanium implants : a histomorphometric study in mini pig maxillae, Clin. Oral Implants Res. 23 (2011) 281–286. doi:10.1111/j.1600-0501.2011.02157.x. [11]

P. Kubasiewicz-Ross, J. Hadzik, M. Dominiak, Osseointegration of zirconia implants with 3 varying surface textures and a titanium implant: A histological and micro-CT study., Adv. Clin. Exp. Med. (2018). doi:10.17219/acem/69246.

[12]

D. Mostafa, M. Aboushelib, Bioactive – hybrid – zirconia implant surface for enhancing osseointegration : an in vivo study, Int. J. Implant Dent. 4 (2018).

[13]

R.J. Kohal, D. Weng, M. Bächle, J.R. Strub, Loaded Custom-Made Zirconia and Titanium

29

ACCEPTED MANUSCRIPT Implants Show Similar Osseointegration: An Animal Experiment, J. Periodontol. 75 (2004) 1262–1268. doi:10.1902/jop.2004.75.9.1262. [14]

T. Albrektsson, H. Hansson, B. Ivarsson, Interface analysis of titanium and zirconium bone implants, Biomaterials. 6 (1985) 97–101. doi:10.1016/0142-9612(85)90070-5.

[15]

J.H. Dubruille, E. Viguier, G. Le Naour, M.T. Dubruille, M. Auriol, Y. Le Charpentier,

I.K. Karoussis, G.E. Salvi, L.J.A. Heitz-Mayfield, U. Bragger, C.H.F. Hämmerle, N.P. Lang,

SC

[16]

RI

the dog., Int. J. Oral Maxillofac. Implants. 14 (1999) 271–277.

PT

Evaluation of combinations of titanium, zirconia, and alumina implants with 2 bone fillers in

Long-term implant prognosis in patients with and without a history of chronic periodontitis: a

NU

10-year prospective cohort study of the ITI Dental Implant System., Clin. Oral Implants Res. 14 (2003) 329–339. doi:934 [pii].

D. Mareci, L.C. Trincă, D. Căilean, R.M. Souto, Corrosion resistance of ZrTi alloys with

MA

[17]

hydroxyapatite-zirconia-silver layer in simulated physiological solution containing proteins for

[18]

PT E

D

biomaterial applications, Appl. Surf. Sci. 389 (2016) 1069–1075. J. Han, G. Hong, H. Lin, Y. Shimizu, Y. Wu, G. Zheng, H. Zhang, K. Sasaki, Biomechanical and histological evaluation of the osseointegration capacity of two types of zirconia implant,

T. Albrektsson, A. Wennerberg, Oral implant surfaces: Part 1--review focusing on topographic

AC

[19]

CE

Int. J. Nanomedicine. Volume 11 (2016) 6507–6516. doi:10.2147/IJN.S119519.

and chemical properties of different surfaces and in vivo responses to them., Int. J. Prosthodont. 17 (2004) 536–543. doi:10.1098/rsta.2009.0062. [20]

Han JM; Hong G; Matsui H; Shimizu Y; Zheng G; Lin H; Sasaki K, The surface characterization and bioactivity of NANOZR in vitro., Dent Mater J. 33 (2014) 210–219.

[21]

D.D. Bosshardt, V. Chappuis, D. Buser, Osseointegration of titanium, titanium alloy and zirconia dental implants: current knowledge and open questions, Periodontol. 2000. 73 (2017) 22–40. doi:10.1111/prd.12179.

30

ACCEPTED MANUSCRIPT [22]

P.I. Brånemark, R. Adell, U. Breine, B.O. Hansson, J. Lindström, A. Ohlsson, Intra-osseous anchorage of dental prostheses. I. Experimental studies., Scand. J. Plast. Reconstr. Surg. 3 (1969) 81–100.

[23]

G. Manzano, L.R. Herrero, J. Montero, Comparison of Clinical Performance of Zirconia Implants and Titanium Implants in Animal Models: A Systematic Review, Int. J. Oral

A. Scarano, M. Piattelli, S. Caputi, G.A. Favero, A. Piattelli, Bacterial Adhesion on

RI

[24]

PT

Maxillofac. Implants. 29 (2014) 311–320. doi:10.11607/jomi.2817.

Commercially Pure Titanium and Zirconium Oxide Disks: An In Vivo Human Study, J.

S. Roehling, M. Astasov-Frauenhoffer, I. Hauser-Gerspach, O. Braissant, H. Woelfler, T.

NU

[25]

SC

Periodontol. 75 (2004) 292–296. doi:10.1902/jop.2004.75.2.292.

Waltimo, H. Kniha, M. Gahlert, In Vitro Biofilm Formation on Titanium and Zirconia Implant

[26]

MA

Surfaces, J. Periodontol. 88 (2017) 298–307. doi:10.1902/jop.2016.160245. Karoline Pardun, 1, Laura Treccani, 1, Eike Volkmann, 1, Philipp Streckbein, 2, Christian

D

Heiss, 4 3, Juergen W Gerlach, 5, Stephan Maendl, 5, and Kurosch Rezwan, Magnesium-

PT E

containing mixed coatings on zirconia for dental implants: mechanical characterization and in vitro behavior, (n.d.). http://journals.sagepub.com/doi/pdf/10.1177/0885328215572428

[27]

CE

(accessed September 11, 2017).

B. Bacchelli, G. Giavaresi, M. Franchi, D. Martini, V. De Pasquale, A. Trirè, M. Fini, R.

AC

Giardino, A. Ruggeri, Influence of a zirconia sandblasting treated surface on peri-implant bone healing: An experimental study in sheep, Acta Biomater. 5 (2009) 2246–2257. [28]

C.G. Moura, R. Pereira, M. Buciumeanu, O. Carvalho, F. Bartolomeu, R. Nascimento, F.S. Silva, Effect of laser surface texturing on primary stability and surface properties of zirconia implants, Ceram. Int. (2017) 0–1. doi:10.1016/j.ceramint.2017.08.058.

[29]

C. Sanon, J. Chevalier, T. Douillard, M. Cattani-Lorente, S.S. Scherrer, L. Gremillard, A new testing protocol for zirconia dental implants, Dent. Mater. 31 (2015) 15–25.

31

ACCEPTED MANUSCRIPT doi:10.1016/j.dental.2014.09.002. [30]

B. Altmann, K. Rabel, R.J. Kohal, S. Proksch, P. Tomakidi, E. Adolfsson, F. Bernsmann, P. Palmero, T. Fürderer, T. Steinberg, Cellular transcriptional response to zirconia-based implant materials, Dent. Mater. 33 (2017) 241–255.

[31]

P.G. Coelho, R. Jimbo, N. Tovar, E.A. Bonfante, Osseointegration: Hierarchical designing

PT

encompassing the macrometer, micrometer, and nanometer length scales, Dent. Mater. 31

M. Liu, J. Zhou, Y. Yang, M. Zheng, J. Yang, J. Tan, Surface modification of zirconia with

SC

[32]

RI

(2015) 37–52. doi:10.1016/j.dental.2014.10.007.

polydopamine to enhance fibroblast response and decrease bacterial activity in vitro: A

[33]

NU

potential technique for soft tissue engineering applications, 136 (2015) 74–83. M. Gahlert, T. Gudehus, S. Eichhorn, E. Steinhauser, H. Kniha, W. Erhardt, Biomechanical

MA

and histomorphometric comparison between zirconia implants with varying surface textures and a titanium implant in the maxilla of miniature pigs, Clin. Oral Implants Res. 18 (2007)

PT E

[34]

D

662–668.

Q. Flamant, F. García Marro, J.J. Roa Rovira, M. Anglada, Hydrofluoric acid etching of dental zirconia. Part 1: Etching mechanism and surface characterization, J. Eur. Ceram. Soc. 36

M.S. Laranjeira, Â. Carvalho, A. Pelaez-Vargas, D. Hansford, M.P. Ferraz, S. Coimbra, E.

AC

[35]

CE

(2016) 121–134. doi:10.1016/j.jeurceramsoc.2015.09.021.

Costa, A. Santos-Silva, M.H. Fernandes, F.J. Monteiro, Modulation of human dermal microvascular endothelial cell and human gingival fibroblast behavior by micropatterned silica coating surfaces for zirconia dental implant applications., Sci. Technol. Adv. Mater. 15 (2014) 025001. doi:10.1088/1468-6996/15/2/025001. [36]

K. Pardun, L. Treccani, E. Volkmann, P. Streckbein, C. Heiss, J.W. Gerlach, S. Maendl, K. Rezwan, Magnesium-containing mixed coatings on zirconia for dental implants: mechanical characterization and in vitro behavior., J. Biomater. Appl. 30 (2015) 104–18.

32

ACCEPTED MANUSCRIPT doi:10.1177/0885328215572428. [37]

H. Li, Y. Xie, K. Li, L. Huang, S. Huang, B. Zhao, Microstructure and wear behavior of graphene nanosheets-reinforced zirconia coating, Ceram. Int. 40 (2014) 12821–12829. doi:10.1016/j.ceramint.2014.04.136.

[38]

M. Liu, J. Zhou, Y. Yang, M. Zheng, J. Yang, J. Tan, Colloids and Surfaces B : Biointerfaces

PT

Surface modification of zirconia with polydopamine to enhance fibroblast response and

RI

decrease bacterial activity in vitro : A potential technique for soft tissue engineering

[39]

SC

applications, 136 (2015) 74–83.

A. Hafezeqoran, R. Koodaryan, Effect of Zirconia Dental Implant Surfaces on Bone

NU

Integration: A Systematic Review and Meta-Analysis, Biomed Res. Int. 2017 (2017). doi:10.1155/2017/9246721.

D.S. Thoma, G.I. Benic, F. Muñoz, R. Kohal, I. Sanz Martin, A.G. Cantalapiedra, C.H.F.

MA

[40]

Hämmerle, R.E. Jung, Histological analysis of loaded zirconia and titanium dental implants: an

[41]

PT E

doi:10.1111/jcpe.12453.

D

experimental study in the dog mandible, J. Clin. Periodontol. 42 (2015) 967–975.

H. Kim, W. Shon, J. Ahn, S. Cha, Y. Park, M.D. Sciences, Comparison of peri-implant bone

CE

formation around injection- molded and machined surface zirconia implants in rabbit tibiae,

[42]

AC

Dent. Mater. J. 34 (2017) 508–515. M.N. Aboushelib, N.A. Salem, N.M.A. El Moneim, Influence of Surface Nano-Roughness on Osseointegration of Zirconia Implants in Rabbit Femur Heads Using Selective Infiltration Etching Technique, J. Oral Implantol. 39 (2013) 583–590. [43]

O. Hoffmann, N. Angelov, G.-G. Zafiropoulos, S. Andreana, Osseointegration of zirconia implants with different surface characteristics: an evaluation in rabbits., Int. J. Oral Maxillofac. Implants. 27 (2012) 352–8.

[44]

F.P. Koch, D. Weng, S. Krämer, S. Biesterfeld, A. Jahn-Eimermacher, W. Wagner,

33

ACCEPTED MANUSCRIPT Osseointegration of one-Piece zirconia implants compared with a titanium implant of identical design: A histomorphometric study in the dog, Clin. Oral Implants Res. 21 (2010) 350–356. [45]

J. Montero, M. Bravo, Y. Guadilla, M. Portillo, L. Blanco, R. Rojo, I. Rosales-Leal, A. LópezValverde, Comparison of Clinical and Histologic Outcomes of Zirconia Versus Titanium Implants Placed in Fresh Sockets: A 5-Month Study in Beagles, Int. J. Oral Maxillofac.

H. Schliephake, T. Hefti, F. Schlottig, P. Gédet, H. Staedt, Mechanical anchorage and peri-

RI

[46]

PT

Implants. 30 (2015) 773–780.

implant bone formation of surface-modified zirconia in minipigs, J. Clin. Periodontol. 37

A. Linares, L. Grize, F. Muñoz, B.E. Pippenger, M. Dard, O. Domken, J. Blanco-Carrión,

NU

[47]

SC

(2010) 818–828.

Histological assessment of hard and soft tissues surrounding a novel ceramic implant: A pilot

[48]

MA

study in the minipig, J. Clin. Periodontol. 43 (2016) 538–546. doi:10.1111/jcpe.12543. S.F.M. Janner, M. Gahlert, D.D. Bosshardt, S. Roehling, S. Milz, F. Higginbottom, D. Buser,

D

D.L. Cochran, Bone response to functionally loaded, two-piece zirconia implants: A

[49]

PT E

preclinical histometric study, Clin. Oral Implants Res. 29 (2018) 277–289. L. Calvo-guirado, J. Gargallo-albiol, R.A. Delgado-ruiz, M. Satorres-nieto, Zirconia with

CE

laser-modified micro- grooved surface vs . titanium implants covered with melatonin stimulates bone formation . Experimental study in tibia rabbits, Clin. Oral Implants Res. 26

[50]

AC

(2015) 1421–1429. doi:10.1111/clr.12472. R.A. Delgado-Ruiz, M. Abboud, G. Romanos, A. Aguilar-Salvatierra, G. Gomez-Moreno, J.L. Calvo-Guirado, Peri-implant bone organization surrounding zirconia-microgrooved surfaces circularly polarized light and confocal laser scanning microscopy study, Clin. Oral Implants Res. 26 (2015) 1328–1337. [51]

R.A. Delgado-ruiz, J.L. Calvo-guirado, Histologic and Histomorphometric Behavior of Microgrooved Zirconia Dental Implants with, Clin. Implant Dent. Relat. Res. 16 (2014) 856–

34

ACCEPTED MANUSCRIPT 872. [52]

J.L. Calvo-Guirado, A. Aguilar-Salvatierra, G. Gomez-Moreno, J. Guardia, R.A. DelgadoRuiz, J.E. Mate-Sanchez de Val, Histological, radiological and histomorphometric evaluation of immediate vs. non-immediate loading of a zirconia implant with surface treatment in a dog model, Clin. Oral Implants Res. 25 (2014) 826–830. M. Brezavšček, A. Fawzy, M. Bächle, T. Tuna, J. Fischer, W. Att, The Effect of UV

PT

[53]

RI

Treatment on the Osteoconductive Capacity of Zirconia-Based Materials., Mater. (Basel,

[54]

SC

Switzerland). 9 (2016). doi:10.3390/ma9120958.

J. Fischer, A. Schott, S. Märtin, Surface micro-structuring of zirconia dental implants, Clin.

[55]

NU

Oral Implants Res. 27 (2016) 162–166. doi:10.1111/clr.12553. H. Xie, S. Shen, M. Qian, F. Zhang, C. Chen, F.R. Tay, Effects of Acid Treatment on Dental

MA

Zirconia: An In Vitro Study, PLoS One. 10 (2015) e0136263. doi:10.1371/journal.pone.0136263.

D

M. Gahlert, S. Röhling, M. Wieland, S. Eichhorn, H. Küchenhoff, H. Kniha, A Comparison

PT E

[56]

Study of the Osseointegration of Zirconia and Titanium Dental Implants. A Biomechanical Evaluation in the Maxilla of Pigs, Clin. Implant Dent. Relat. Res. 12 (2010) 297–305.

V.T. Vu, G.-J. Oh, K.-D. Yun, H.-P. Lim, J.-W. Kim, T.P.T. Nguyen, S.-W. Park, Acid

AC

[57]

CE

doi:10.1111/j.1708-8208.2009.00168.x.

etching of glass-infiltrated zirconia and its biological response, J. Adv. Prosthodont. 9 (2017) 104–109. [58]

J.Y. Thompson, B.R. Stoner, J.R. Piascik, R. Smith, Adhesion/cementation to zirconia and other non-silicate ceramics: Where are we now?, Dent. Mater. 27 (2011) 71–82. doi:10.1016/j.dental.2010.10.022.

[59]

L.F. Cooper, Y. Zhou, J. Takebe, J. Guo, A. Abron, A. Holm??n, J.E. Ellingsen, Fluoride modification effects on osteoblast behavior and bone formation at TiO2 grit-blasted c.p.

35

ACCEPTED MANUSCRIPT titanium endosseous implants, Biomaterials. 27 (2006) 926–936. doi:10.1016/j.biomaterials.2005.07.009. [60]

J. Oliva, X. Oliva, J.D. Oliva, Five-year success rate of 831 consecutively placed Zirconia dental implants in humans: a comparison of three different rough surfaces., Int. J. Oral Maxillofac. Implants. 25 (2010) 336–44. G. Oh, J. Yoon, V.T. Vu, M. Ji, J. Kim, J. Kim, E. Yim, J. Bae, C. Park, K. Yun, H. Lim, S.

PT

[61]

RI

Park, J.G. Fisher, Surface Characteristics of Bioactive Glass-Infiltrated Zirconia with Different Hydrofluoric Acid Etching Conditions, J. Nanosci. Nanotechnol. 17 (2017) 2645–2648.

U. Hempel, T. Hefti, M. Kalbacova, C. Wolf-Brandstetter, P. Dieter, F. Schlottig, Response of

NU

[62]

SC

doi:10.1166/jnn.2017.13323.

osteoblast-like SAOS-2 cells to zirconia ceramics with different surface topographies, Clin.

[63]

MA

Oral Implants Res. 21 (2010) 174–181.

C. Bergemann, K. Duske, J.B. Nebe, A. Schöne, U. Bulnheim, H. Seitz, J. Fischer,

D

Microstructured zirconia surfaces modulate osteogenic marker genes in human primary

[64]

PT E

osteoblasts., J. Mater. Sci. Mater. Med. 26 (2015) 5350. doi:10.1007/s10856-014-5350-x. A. Wennerberg, T. Albrektsson, Effects of titanium surface topography on bone integration: a

CE

systematic review, Clin. Oral Implants Res. 20 (2009) 172–184. doi:10.1111/j.1600-

[65]

AC

0501.2009.01775.x.

N. Saulacic, R. Erdösi, D.D. Bosshardt, R. Gruber, D. Buser, Acid and Alkaline Etching of Sandblasted Zirconia Implants: A Histomorphometric Study in Miniature Pigs, Clin. Implant Dent. Relat. Res. 16 (2014) 313–322. doi:10.1111/cid.12070.

[66]

Y. Zhang, B.R. Lawn, K.A. Malament, P. Van Thompson, E.D. Rekow, Damage accumulation and fatigue life of particle-abraded ceramics., Int. J. Prosthodont. 19 (n.d.) 442–8. http://www.ncbi.nlm.nih.gov/pubmed/17323721 (accessed November 14, 2018).

[67]

I.L. Aurélio, A.M.E. Marchionatti, A.F. Montagner, L.G. May, F.Z.M. Soares, Does air

36

ACCEPTED MANUSCRIPT particle abrasion affect the flexural strength and phase transformation of Y-TZP? A systematic review and meta-analysis, Dent. Mater. 32 (2016) 827–845. doi:10.1016/j.dental.2016.03.021. [68]

G.K.R. Pereira, L.F. Guilardi, K.S. Dapieve, C.J. Kleverlaan, M.P. Rippe, L.F. Valandro, Mechanical reliability, fatigue strength and survival analysis of new polycrystalline translucent zirconia ceramics for monolithic restorations, J. Mech. Behav. Biomed. Mater. 85 (2018) 57–

T. Sriamporn, N. Thamrongananskul, C. Busabok, S. Poolthong, M. Uo, J. Tagami, Dental

RI

[69]

PT

65. doi:10.1016/J.JMBBM.2018.05.029.

zirconia can be etched by hydrofluoric acid., Dent. Mater. J. 33 (2014) 79–85.

H. Sato, K. Yamada, G. Pezzotti, M. Nawa, S. Ban, Mechanical Properties of Dental Zirconia

NU

[70]

SC

http://www.ncbi.nlm.nih.gov/pubmed/24492116 (accessed November 14, 2018).

Ceramics Changed with Sandblasting and Heat Treatment, 2008.

MA

https://www.jstage.jst.go.jp/article/dmj/27/3/27_3_408/_pdf/-char/en (accessed November 14, 2018).

A. Henningsen, R. Smeets, R. Heuberger, O.T. Jung, H. Hanken, M. Heiland, C. Cacaci, C.

D

[71]

PT E

Precht, Changes in surface characteristics of titanium and zirconia after surface treatment with ultraviolet light or non-thermal plasma, Eur. J. Oral Sci. (2018). T. Tuna, M. Wein, B. Altmann, T. Steinberg, J. Fischer, W. Att, Effect of ultraviolet

CE

[72]

photofunctionalisation on the cell attractiveness of zirconia implant materials., Eur. Cell.

AC

Mater. 29 (2015) 82-94; discussion 95–6. http://www.ncbi.nlm.nih.gov/pubmed/25612543 (accessed November 12, 2018). [73]

T. Tuna, M. Wein, M. Swain, J. Fischer, W. Att, Influence of ultraviolet photofunctionalization on the surface characteristics of zirconia-based dental implant materials, Dent. Mater. 31 (2015) e14–e24. doi:10.1016/j.dental.2014.10.008.

[74]

D. Liu, J.P. Matinlinna, J.K.-H. Tsoi, E.H.N. Pow, T. Miyazaki, Y. Shibata, C.-W. Kan, A new modified laser pretreatment for porcelain zirconia bonding, Dent. Mater. 29 (2013) 559–565.

37

ACCEPTED MANUSCRIPT doi:10.1016/j.dental.2013.03.002. [75]

Y. Yang, J. Zhou, X. Liu, M. Zheng, J. Yang, J. Tan, Ultraviolet light-treated zirconia with different roughness affects function of human gingival fibroblasts in vitro: The potential surface modification developed from implant to abutment, J. Biomed. Mater. Res. - Part B Appl. Biomater. 103 (2015) 116–124. doi:10.1002/jbm.b.33183. J.P. Parry, J.D. Shephard, D.P. Hand, C. Moorhouse, N. Jones, N. Weston, Laser

PT

[76]

RI

micromachining of zirconia (Y-TZP) ceramics in the picosecond regime and the impact on material strength, Int. J. Appl. Ceram. Technol. 8 (2011) 163–171. doi:10.1111/j.1744-

L. Hao, J. Lawrence, K.S. Chian, Osteoblast cell adhesion on a laser modified zirconia based

NU

[77]

SC

7402.2009.02420.x.

bioceramic, J. Mater. Sci. Mater. Med. 16 (2005) 719–726. doi:10.1007/s10856-005-2608-3. K.M. Hotchkiss, G.B. Reddy, S.L. Hyzy, Z. Schwartz, B.D. Boyan, R. Olivares-Navarrete,

MA

[78]

Titanium surface characteristics, including topography and wettability, alter macrophage

D

activation, Acta Biomater. 31 (2016) 425–434. doi:10.1016/j.actbio.2015.12.003. A.S.D. Al-Radha, D. Dymock, C. Younes, D. O’Sullivan, Surface properties of titanium and

PT E

[79]

zirconia dental implant materials and their effect on bacterial adhesion, J. Dent. 40 (2012)

Y. Cho, H. J, H. Ryoo, D. Kim, J. Park, J. Han, Osteogenic responses to zirconia with

AC

[80]

CE

146–153. doi:10.1016/j.jdent.2011.12.006.

hydroxyapatite coating by aerosol deposition, J. Dent. Res. 94 (2015) 491–499. [81]

G. Wang, F. Meng, C. Ding, P.K. Chu, X. Liu, Microstructure, bioactivity and osteoblast behavior of monoclinic zirconia coating with nanostructured surface, Acta Biomater. 6 (2010) 990–1000. doi:10.1016/j.actbio.2009.09.021.

[82]

Y. Chen, X. Zheng, Y. Xie, C. Ding, H. Ruan, C. Fan, Anti-bacterial and cytotoxic properties of plasma sprayed silver-containing HA coatings, J. Mater. Sci. Mater. Med. 19 (2008) 3603– 3609. doi:10.1007/s10856-008-3529-8.

38

ACCEPTED MANUSCRIPT [83]

S. Schienle, A. Al-Ahmad, R.J. Kohal, F. Bernsmann, E. Adolfsson, L. Montanaro, P. Palmero, T. Fürderer, J. Chevalier, E. Hellwig, L. Karygianni, Microbial adhesion on novel yttria-stabilized tetragonal zirconia (Y-TZP) implant surfaces with nitrogen-doped hydrogenated amorphous carbon (a-C:H:N) coatings, Clin. Oral Investig. (2015) 1–14. doi:10.1007/s00784-015-1655-5. K. Pardun, L. Treccani, E. Volkmann, P. Streckbein, C. Heiss, G.L. Destri, G. Marletta, K.

PT

[84]

Rezwan, Mixed zirconia calcium phosphate coatings for dental implants: Tailoring coating

RI

stability and bioactivity potential, Mater. Sci. Eng. C. 48 (2015) 337–346.

Y.T. Liu, T.M. Lee, T.S. Lui, Enhanced osteoblastic cell response on zirconia by bio-inspired

NU

[85]

SC

doi:10.1016/j.msec.2014.12.031.

surface modification, Colloids Surfaces B Biointerfaces. 106 (2013) 37–45. A. Kirsten, A. Hausmann, M. Weber, J. Fischer, H. Fischer, Bioactive and Thermally

MA

[86]

Compatible Glass Coating on Zirconia Dental Implants, J. Dent. Res. 94 (2015) 297–303.

M. Catauro, F. Bollino, F. Papale, S. Vecchio Ciprioti, Investigation on bioactivity,

PT E

[87]

D

doi:10.1177/0022034514559250.

biocompatibility, thermal behavior and antibacterial properties of calcium silicate glass

CE

coatings containing Ag, J. Non. Cryst. Solids. 422 (2015) 16–22. doi:10.1016/j.jnoncrysol.2015.04.037. D. Mushahary, C. Wen, J.M. Kumar, J. Lin, N. Harishankar, P. Hodgson, G. Pande, Y. Li,

AC

[88]

Collagen type-I leads to in vivo matrix mineralization and secondary stabilization of Mg–Zr– Ca alloy implants, Colloids Surfaces B Biointerfaces. 122 (2014) 719–728. doi:10.1016/j.colsurfb.2014.08.005. [89]

E.M.M. Ewais, A.M.M. Amin, Y.M.Z. Ahmed, E.A. Ashor, U. Hess, K. Rezwan, Combined effect of magnesia and zirconia on the bioactivity of calcium silicate ceramics at C\S ratio less than unity, Mater. Sci. Eng. C. 70 (2017) 155–160. doi:10.1016/j.msec.2016.08.057.

39

ACCEPTED MANUSCRIPT [90]

N. Garmendia, L. Bilbao, R. Muñoz, G. Imbuluzqueta, A. García, I. Bustero, L. Calvo-Barrio, J. Arbiol, I. Obieta, Zirconia coating of carbon nanotubes by a hydrothermal method., J. Nanosci. Nanotechnol. 8 (2008) 5678–83. http://www.ncbi.nlm.nih.gov/pubmed/19198288 (accessed November 9, 2018).

[91]

W. Kou, T. Akasaka, F. Watari, G. Sjögren, An In Vitro Evaluation of the Biological Effects

PT

of Carbon Nanotube-Coated Dental Zirconia, ISRN Dent. 2013 (2013) 1–6.

Reproducibility of ZrO2-based freeze casting for biomaterials, Mater. Sci. Eng. C. 61 (2016) 105–112. doi:10.1016/J.MSEC.2015.12.012.

I.C. Lavos-Valereto, B. König, C. Rossa, E. Marcantonio, A.C. Zavaglia, A study of

NU

[93]

SC

[92]

RI

doi:10.1155/2013/296727.

histological responses from Ti-6Al-7Nb alloy dental implants with and without plasma-

[94]

MA

sprayed hydroxyapatite coating in dogs., J. Mater. Sci. Mater. Med. 12 (2001) 273–6. M.N. Aboushelib, R. Shawky, Osteogenesis ability of CAD/CAM porous zirconia scaffolds

D

enriched with nano-hydroxyapatite particles, Int. J. Implant Dent. 3 (2017) 21.

[95]

PT E

doi:10.1186/s40729-017-0082-6.

A. Le Ray, H. Gautier, J. Bouler, P. Weiss, C. Merle, A new technological procedure using

CE

sucrose as porogen compound to manufacture porous biphasic calcium phosphate ceramics of appropriate micro- and macrostructure, 36 (2010) 93–101.

[96]

AC

doi:10.1016/j.ceramint.2009.07.001. J. Yang, R. Sultana, P. Ichim, X. Hu, Z. Huang, Micro-porous calcium phosphate coatings on load-bearing zirconia substrate : Processing , property and application, Ceram. Int. 39 (2013) 6533–6542. doi:10.1016/j.ceramint.2013.01.086. [97]

H. Lee, S.M. Dellatore, W.M. Miller, P.B. Messersmith, Mussel-Inspired Surface Chemistry for Multifunctional Coatings, 318 (2008) 426–430. doi:10.1126/science.1147241.MusselInspired.

40

ACCEPTED MANUSCRIPT [98]

M. Xu, D. Zhai, L. Xia, H. Li, S. Chen, B. Fang, J. Chang, C. Wu, Hierarchical bioceramic scaffolds with 3D-plotted macropores and mussel-inspired surface nanolayers, Nanoscale. 12 (2016) 13790–13803. doi:10.1039/c6nr01952h.

[99]

Y. Liu, T. Lee, T. Lui, Colloids and Surfaces B : Biointerfaces Enhanced osteoblastic cell response on zirconia by bio-inspired surface modification, Colloids Surfaces B Biointerfaces.

PT

106 (2013) 37–45. doi:10.1016/j.colsurfb.2013.01.023.

RI

[100] S. Priyadarsini, S. Mukherjee, M. Mishra, Nanoparticles used in dentistry: A review., J. Oral

SC

Biol. Craniofacial Res. 8 (2018) 58–67. doi:10.1016/j.jobcr.2017.12.004. [101] Y. Xie, H. Li, C. Ding, X. Zheng, K. Li, Effects of graphene plates’ adoption on the

NU

microstructure, mechanical properties, and in vivo biocompatibility of calcium silicate coating., Int. J. Nanomedicine. 10 (2015) 3855–63. doi:10.2147/IJN.S77919.

MA

[102] B.H. Cho, W.B. Ko, Preparation of graphene-ZrO2 nanocomposites by heat treatment and photocatalytic degradation of organic dyes., J. Nanosci. Nanotechnol. 13 (2013) 7625–30.

PT E

D

http://www.ncbi.nlm.nih.gov/pubmed/24245304 (accessed November 7, 2018). [103] S. Ferraris, M. Miola, Surface modification of bioactive glasses, in: Surf. Tailoring Inorg. Mater. Biomed. Appl., Bentham Science Publishers Ltd., Applied Science and Technology

CE

Department - DISAT, Politecnico di Torino, C.so Duca degli Abruzzi 24, 10129, Torino, Italy,

AC

2012: pp. 392–405. doi:10.2174/978160805462611201010392. [104] Y. Zhang, J.W. Kim, Graded zirconia glass for resistance to veneer fracture., J. Dent. Res. 89 (2010) 1057–62. doi:10.1177/0022034510375289. [105] Y. Zhang, R. Legeros, J. Kim, US8703294 B2 - Bioactive graded zirconia-based structures, 2014. [106] Y. Zhang, J. Kim, V.P. Thompson, US7858192 B2 - Graded glass/ceramic/glass structures for damage resistant ceramic dental and orthopedic prostheses, 2010. [107] D. Fabris, J.C.M. Souza, F.S. Silva, M. Fredel, J. Mesquita-Guimarães, Y. Zhang, B.

41

ACCEPTED MANUSCRIPT Henriques, Thermal residual stresses in bilayered, trilayered and graded dental ceramics, Ceram. Int. 43 (2017). doi:10.1016/j.ceramint.2016.11.209. [108] D. Fabris, J.C.M. Souza, F.S. Silva, M. Fredel, J. Mesquita-Guimarães, Y. Zhang, B. Henriques, The bending stress distribution in bilayered and graded zirconia-based dental ceramics, Ceram. Int. 42 (2016) 11025–11031. doi:10.1016/j.ceramint.2016.03.245.

PT

[109] B. Henriques, D. Fabris, J.C.M. Souza, F.S. Silva, J. Mesquita-Guimarães, Y. Zhang, M.

RI

Fredel, Influence of interlayer design on residual thermal stresses in trilayered and graded all-

SC

ceramic restorations, Mater. Sci. Eng. C. 71 (2017). doi:10.1016/j.msec.2016.11.087. [110] Y. Zhang, H. Chai, B.R. Lawn, Graded structures for all-ceramic restorations., J. Dent. Res.

NU

(2010). doi:10.1177/0022034510363245.

[111] Y. Zhang, M.-J. Sun, D. Zhang, Designing functionally graded materials with superior load-

MA

bearing properties., Acta Biomater. 8 (2012) 1101–8. doi:10.1016/j.actbio.2011.11.033. [112] J.W. Kim, L. Liu, Y. Zhang, Improving the resistance to sliding contact damage of zirconia

PT E

D

using elastic gradients, J. Biomed. Mater. Res. - Part B Appl. Biomater. 94 (2010) 347–352. doi:10.1002/jbm.b.31657.

[113] Y. Zhang, J. Kim, Graded structures for damage resistant and aesthetic all-ceramic

CE

restorations, Dent. Mater. 25 (2009) 781–790. doi:10.1016/j.dental.2009.01.002.

AC

[114] Y. Zhang, L. Ma, Optimization of ceramic strength using elastic gradients, Acta Mater. 57 (2009) 2721–2729. doi:10.1016/j.actamat.2009.02.037. [115] I. Mihatovic, V. Golubovic, J. Becker, F. Schwarz, Bone tissue response to experimental zirconia implants, Clin. Oral Investig. 21 (2017) 523–532. doi:10.1007/s00784-016-1904-2. [116] R.-J. Kohal, S.B.M. Patzelt, F. Butz, H. Sahlin, One-piece zirconia oral implants: one-year results from a prospective case series. 2. Three-unit fixed dental prosthesis (FDP) reconstruction, J. Clin. Periodontol. 40 (2013) 553–562. doi:10.1111/jcpe.12093.

42

ACCEPTED MANUSCRIPT

Highlights

- Machined zirconia and titanium implants have shown an adequate osseointegration - Treated zirconia implants have shown improved BIC% over machined ones

PT

- No surface treatment has been claimed as first choice for zirconia’s osseointegration

AC

CE

PT E

D

MA

NU

SC

RI

-Bioactive graded structures can improve zirconia´s bioactivity and osseointegration.

43