Thirty Years of Translational Research in Zirconia Dental Implants: A Systematic Review of the Literature

Zirconium dioxide is one of the most widely used ceramic materials because of its unique qualities. Zirconia (Zr) ceramics were first introduced to implant dentistry in the form of coatings onto metal-based endosseous implants to improve osseointegration. Over the past 3 decades, various forms of ceramic coatings, including bioactive ceramics (hydroxyapatite, bioactive glasses) and inert ceramics (aluminium oxide and zirconium oxide), have been used on dental implants.¹  Thanks to translational research in Zr biomaterials, dental implants made of yttria-tetragonal zirconia polycrystals (Y-TZP) have emerged as an attractive metal-free alternative to Ti implants.^2–4  Zirconia-yttria ceramics, also known as yttria-stabilized tetragonal zirconia polycrystals (Y-TZP), have attracted considerable attention and have been proposed as a viable option for dental implant materials because of their excellent mechanical properties, good biocompatibility, and esthetically acceptable color.⁵  Thirty years of transitional research in Zr ceramics has led to significant improvements in the biomedical field, especially in dental implantology. Now, Zr is used not only as a coating material but also to manufacture dental implants that have improved esthetics and function for patients.

In vitro and in vivo animal studies, investigating different aspects of Y-TZP implants, have shown promising results that have strongly encouraged their clinical use in humans.^2–4,6  Contrary to Ti implants that have shown some immune reactions,^7–9  Zr is highly biocompatible, with no local or systemic toxic effects of its implantation.^10,11  It has become the first choice for patients with metal hypersensitivity issues (especially with Ti implants) for their oral rehabilitation needs.¹²  Reduced inflammatory infiltrates, decreased microvessel density, and a low bacterial colonization potential were observed around Zr when compared with Ti implants.¹³  Biomechanical investigations on Zr oral implants using a 3-dimensional finite element analysis showed that Y-TZP implants could sustain chewing stresses and have similar stress distribution as commercially pure Ti.^4,11  The outcomes of animal research, in vitro studies, and case reports using Zr implants, abutments, and frameworks on humans have been encouraging, with high success rates.^{2–4,14–16} 

The use of animal models is an essential step in the testing of new biomaterials before their use in humans. Preclinical animal models allow high-magnification histological measurement and quantification of the amount of bone that forms in contact with the implant surface. Biomedical research has used many different kinds of animal models in dental implant research, each having differences in bone remodeling and bone architecture, with potential advantages and disadvantages.¹⁷  Investigators have used the tibia of rabbits,^3,18–20  tibia of minipigs,⁶  mandible of minipigs,²¹  maxilla of pigs,²²  maxilla of monkeys,¹¹  mandible of dogs,²³  and jaws and femur of sheep^24,25  to investigate the bone-implant contact (BIC) of Zr implants.

During the past 15 years, there has been a gradual increase in the use of Zr ceramic dental implants, mainly because of their esthetic qualities and provision of a metal-free approach, especially for patients who show concern for metal sensitivity and would like to avoid metal restorations in their mouth, including amalgam restorations and Ti implants. The aim of the review was to investigate BIC around Zr implants in preclinical animal models. The review will highlight the importance of preclinical experimental models and the preferences of researchers in using different animal models while investigating Zr ceramics. The analysis will provide the current picture of the biomechanical qualities and performance of Zr ceramic implants using translation models. Although the empirical evidence suggests that Zr implants can be a viable treatment option for Ti implants in particular cases, the clinical performance of the Zr ceramic implants is still debated, as there are no recommendations, protocols, or consensus for clinicians to follow to achieve long-term successful clinical outcomes of Zr implants. The article will invite the reader to critically review the reasons and the logical basis for choosing Zr implants, while keeping in mind the success and limitations of the biomaterial as reflected in the translation research over the past 30 years.

To recognize studies suitable for inclusion in this systemic review, internationally published literature addressing Zr ceramic implants and studies investigating percentage BIC in (%BIC) preclinical animal models published up until July 2016 were included in the review. A computer search of electronic databases, primarily PubMed, was performed with the following keywords: “zirconia ceramics AND animal trials,” “ceramic implants AND animal trials,” “zirconia AND animal trials,” “zirconia AND in vivo animal trials,” without any language restriction. However, the search was limited to animal trials discussing %BIC around Zr implants/discs. Manual searches of the bibliographies of all the retrieved articles were also performed to include additional eligible publications. The literature was screened by 2 authors (A.S. and S.Z.) for relevancy. The search strategy is given in the flow diagram (Figure 1).

• Inclusion criteria

• 1. • Studies investigated %BIC around Zr implants/discs

  2. • In vivo animal trials

• Exclusion criteria

• 1. • %BIC around Zr implants/discs was not studied

  2. • Not an animal study

  3. • Review article/case reports

This search resulted in 132 articles (reviews, in vivo animal, and laboratory studies) of potential interest. We restricted our search terms to “zirconia/ceramic,” “bone-implant-contact” and “animal trials” and found 29 relevant publications, which were then selected for full-text reading. Reasons for exclusion included the article was not an animal study, the article was a review article, and the article did not discuss BIC around Zr implants/discs. Most of the studies investigated BIC around Zr in rabbits (30%), pigs (around 20%), dogs, sheep, and rats. A detailed description of the %BIC, observation period, and the method of detection is presented in the Table.

Zirconia ceramics as a dental implant material have been under investigation for the past 4 decades. Zirconia has shown predictable osseointegration, cell metabolism, and positive tissue response in the in vivo animal studies. Studies have shown good biocompatibility for Zr implants under loaded conditions.^3,4  The review of the literature demonstrates that a wide range of animal models have been used to evaluate osseointegration of Zr implants. Most of the researchers used rabbits and minipigs to assess Zr implants. Rabbit is the most commonly used preclinical animal for dental implant studies because of the ease of handling and the low costs, but it is the least similar to human bone. The domestic pig demonstrates a strong similarity to human bone, but the pig may be difficult to manage because of its size and the expenses.¹⁷  The use of animal models such as nonhuman primates, rats, beagle dogs, and mice for guided tissue regeneration experimentation is well documented and has provided most of the histologic data on periodontal tissue healing, thus demonstrating that animal models are suitable for periodontal studies.⁴⁶ 

Zirconia has shown similar %BIC to that of Ti implants in most of the studies.^21,30,37  Koch and colleagues³⁷  compared 1-piece Zr dental implants with Ti implant screws in a dog model and found that the BIC of Zr implants was statistically equivalent to Ti implants. Another study of 1-piece Zr implants in minipigs found similar results.²¹  Lee and colleagues³⁰  in a beagle dog model demonstrated excellent esthetic and soft-tissue outcomes of 1-piece Zr implants. However, the authors also stressed the need for well-designed, long-term clinical trials to show peri-implant bone outcomes and clinical performance of 1-piece Zr implants in functional loading conditions.

Some recent studies have also reported poorer osseointegration for Zr implants (59.3% after 4 weeks of healing and 67.1% after 12 weeks of healing) when compared with Ti implants (64.1% after 4 weeks of healing and 73.6% after 12 weeks of healing) in the domestic pig model.³⁵  A recent study investigated %BIC around 1-piece Zr and Ti implants placed in the jaws and femurs of domestic sheep.²⁵  They showed superior values for %BIC for Zr compared with Ti implants after 12 weeks of healing in the sheep mandible and femur. The femur implants were submerged and unloaded; the mandibular implants were placed using a 1-stage transgingival protocol and were nonsubmerged implants. However, a higher failure rate of 1-piece Zr implants in the clinical condition was noted, as demonstrated in other clinical studies.⁴⁷ 

In the quest to achieve more predictable osseointegration, especially in difficult clinical sites, researchers have attempted to alloy zirconium to Ti.^48,49  Comparable results have been reported with this new Ti-Zr alloy compared with traditional commercially pure Ti implants. The recombinant human bone morphogenic protiens-2 (rhBMP-2) gel has also been applied to the Zr implant surface to enhance the local bone formation and the speedy recovery of the prepared implant site for early osseointegration.³⁰  The researchers found similar %BIC to the Zr implants with rhBMP-2 gel; however, improved healing of the implant site was observed. A recent report has demonstrated excellent esthetic and soft-tissue outcomes of 1-piece Zr implants.³⁰  The authors stressed the need for well-designed, long-term clinical trials to demonstrate peri-implant bone outcomes and clinical performance of 1-piece Zr implants.

Implant surface topography is the key determinant of successful osseointegration and can influence clinical results. Surface properties of different implants may vary because of the differences in manufacturing and coating techniques used in the preparation of implants. The literature on the risk of reduction of the life span of the Zr ceramics associated with the surface alterations is scarce.⁵⁰  Research has shown that the surface modifications of an implant with Zr may have a positive effect on bone-implant contact.⁵¹  However, research has also reported that water diffusion can occur that can alter the stability of the tetragonal phase due to the humid atmosphere.⁵²  Furthermore, grinding or sandblasting of the Zr surface may be responsible for alteration in the phase integrity of the material that can increase the susceptibility to the aging of the material.⁵³  Studies have shown that high cyclic contact loading during mastication can initiate crack nucleation and propagation by subcritical crack growth.⁵⁴  In addition, manufacturing imperfections and chipping of thread tips of Zr implants may also affect successful osseointegration and can result in implant failure (Figure 2). So far, the fracture of the material and cracks have been attributed as the major technical complications related to Zr implants. These cracks during loading conditions can propagate and may lead to early implant failure.^55,56  Bending moment can induce forces combined with lateral occlusal loading forces and can result in implant failure during function, as can be seen in a scanning electron microscopy image of a fractured proto-type Zr implant (Figures 3 and 4). It is well established that the structural integrity of the Zr can be compromised in the presence of humidity, where the transition from the tetragonal to the monoclinic polymorph of Zr is accelerated.

This review of the literature shows that preclinical animal models can be successfully used to investigate osseointegration around Zr ceramics. Results of the reviewed studies demonstrated excellent %BIC around Zr implants. However, it should be noted that most of the studies investigated %BIC/removal torque under nonloading conditions, and results would have been somewhat different in functional loading situations due to inherent limitations of Zr ceramics, as discussed by Daou⁵³  and Bozkaya et al.⁵⁷  It should also be acknowledged that Zr is a brittle ceramic and is prone to structural imperfections during its manufacture; hence, it is suggested that strict quality standards should be adopted while micromachining Zr implant surfaces. This could be verified by a number of reports that have discussed Zr implant fracture during placement or during the function.^55,58  To date, translational research has answered many questions related to osseointegration of Zr implants, and hence Zr has shown significant improvements in its mechanical properties. Nevertheless, structural and mechanical properties of Zr dental implants still require improvements to withstand loading conditions for the long-term success of dental implants in clinical settings. Until we accomplish the challenge of manufacturing well-designed, structurally strong 2-piece Zr implants, which is most appropriate for the long-term clinical success of the dental implants, the general use of Zr to replace missing teeth should be carefully appraised. Controlled trials are needed to evaluate the performance of Zr implants in clinical conditions using implants designed and manufactured via novel techniques that enhance the biomechanical properties of Zr.

Abbreviations

%BIC

percentage bone-implant contact

BIC

bone-implant contact

APC

anodic plasma-chemical treatment

BV

bone volume

Cap

calcium phosphate

CP

commercially pure

CS

chondroitin sulfate

CT

computerized tomography

mds

modified surface

Ox

oxide

PIM

powder injection molded

pQCT

peripheral quantitative computer tomography

rBVD

relative peri-implant bone level density

rhBMP-2

recombinant human bone morphogenic protein–2

RT/RTQ

removal torque

SEM

scanning electron microscopy

SIE

selective infiltration–etched

SLA

sandblasted-large grit-acid etched

Ti

titanium

TV

trabecular volume

Y-TZP

yttria-tetragonal zirconia polycrystals

Zr

zirconia

The authors declare that they have no conflict of interest.