Polyetheretherketone (PEEK) has been suggested as an alternative to replace titanium as a dental implant material. However, PEEK's bioactivity and osseointegration are debatable. This review has systematically analyzed studies that have compared PEEK (or PEEK-based) implants with titanium implants so that its feasibility as a possible replacement for titanium can be determined. The focused question was: “Are the bioactivity and osseointegration of PEEK implants comparable to or better than titanium implants?” Using the key words “dental implant,” “implant,” “polyetheretherketone,” “PEEK,” and “titanium” in various combinations, the following databases were searched electronically: PubMED/MEDLINE, Embase, Google Scholar, ISI Web of Knowledge, and Cochrane Database. 5 in vitro and 4 animal studies were included in the review. In 4 out of 5 in vitro studies, titanium exhibited more cellular proliferation, angiogenesis, osteoblast maturation, and osteogenesis compared to PEEK; one in vitro study observed comparable outcomes regardless of the implant material. In all animal studies, uncoated and coated titanium exhibited a more osteogenic behavior than did uncoated PEEK, while comparable bone-implant contact was observed in HA-coated PEEK and coated titanium implants. Unmodified PEEK is less osseoconductive and bioactive than titanium. Furthermore, the majority of studies had multiple sources of bias; hence, in its unmodified form, PEEK is unsuitable to be used as dental implant. Significantly more research and long-term trials must focus on improving the bioactivity of PEEK before it can be used as dental implant. More comparative animal and clinical studies are warranted to ascertain the potential of PEEK as a viable alternative to titanium.

Introduction

An endosseous dental implant is a device surgically inserted into the jaw bone to support a prosthodontic or orthodontic appliance.1  Titanium is the most commonly used dental implant material.2  However, it has a number of drawbacks: First, being nonesthetic, it discolors the underlying gingival of thin biotype.3  Second, because the modulus of elasticity of titanium is higher than that of bone, titanium may cause bone resorption by shielding the alveolar bone from occlusal stresses that are needed to maintain bone volume—a phenomenon known as “stress shielding.”4  Furthermore, there have been cases of titanium allergy in patients receiving dental implant.5  Therefore, alternatives to titanium are being studied. Zirconia (zirconium oxide), an esthetic ceramic material, is a possible replacement for titanium implants. However, since its modulus of elasticity is much higher than that of bone, it may lead to stress shielding.6 

More recently, polymeric implant materials have been developed. Polyetheretherketone (PEEK) is a tooth-colored polymer, produced from the step-growth alkylation reaction of bisphenolates, and it has multiple applications in orthopedics.7  PEEK has been used as an implant material in spinal surgery, fracture fixation devices, joint replacement, and maxillofacial surgery.811  In dentistry, PEEK has been used in the construction of CAD/CAM-milled fixed and removable bridges12  as well as removable dentures and crowns.13  Because of PEEK's superior esthetics and modulus of elasticity—close to that of the human bone—it has been proposed as a dental implant material as well.14  However, the potential of PEEK to replace titanium as dental implant material is still debatable. While some studies suggest that unmodified PEEK has osseoconductive properties similar to titanium,15  others suggest that it is does not promote mature osteoblast differentiation as much as does titanium.16  Therefore, this review systematically analyzed studies that have compared PEEK or PEEK-based implants with titanium implants to determine its feasibility as a possible replacement for titanium.

Materials and Methods

Focused question

According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the following focused question was constructed according to the Participants Intervention Control Outcomes principle17: “Are the bioactivity and osseointegration of PEEK implants comparable to or better than titanium implants?”

Selection criteria

The following inclusion criteria were used: (1) studies on osseointegration and/or bioactivity of PEEK (modified or unmodified) and titanium implants, (2) human trials, (3) animal studies, (4) cell-culture (in vitro) studies, and (5) articles in English. The exclusion criteria were: (1) letters to the editor, (2) reviews, and (3) short communications.

Search methodology

Using the keywords “dental implant,” “implant,” “polyetheretherketone,” “PEEK,” and “titanium” in various combinations, the following databases were searched electronically: PubMED/MEDLINE, Embase, Google Scholar, ISI Web of Knowledge, and Cochrane Database. Two reviewers (S.N. and Z.K.) searched independently, according to the inclusion and exclusion criteria. A secondary search was conducted by going through the reference lists of articles obtained in the primary search. Any disagreements were settled by a third reviewer (M.S.Z).

Results

Search results

As illustrated in the Figure, of the 25 articles obtained following the primary search, full texts of 11 articles were read. Two articles were excluded for not meeting the inclusion criteria. Hence, 9 articles (5 in vitro studies and 4 animal studies) were included in the review.15,16,1820  The general characteristics and outcomes of the included in vitro and animal studies are summarized in Tables 1 and 2, respectively.

Figure

The search methodology employed for this review.

Figure

The search methodology employed for this review.

Table 1

Methodology, duration, control, and test implant materials and conclusions of included in vitro studies*

Methodology, duration, control, and test implant materials and conclusions of included in vitro studies*
Methodology, duration, control, and test implant materials and conclusions of included in vitro studies*
*

PEEK indicates polyetheretherketone; CFR, carbon fiber reinforced.

Table 2

Study design, number of animals, duration, site of implantation, control and test implants, and outcomes of the included animal studies*

Study design, number of animals, duration, site of implantation, control and test implants, and outcomes of the included animal studies*
Study design, number of animals, duration, site of implantation, control and test implants, and outcomes of the included animal studies*
*

PEEK indicates polyetheretherketone; CFR, carbon fiber reinforced.

Number unknown.

Main outcomes of selected studies

In 4 out of 5 in vitro studies, titanium exhibited stimulated more cellular proliferation, angiogenesis, osteoblast maturation, and osteogenesis compared to PEEK,16,1820  and comparable outcomes were observed in one in vitro study regardless of the implant material.15  In all animal studies, uncoated and coated titanium exhibited a more osteogenic behavior than did uncoated PEEK,2124  while comparable bone-implant contact was observed in HA-coated PEEK and coated titanium implants.21 

Discussion

Osseointegration of implants depends on a number of factors: bone volume, implant geometry, surface topography, systemic health of the patient, and local factors (such as oral hygiene and smoking habits) are all critical for success of implant therapy.25  Implant surface characteristics are vital for instituting primary stability after placement into the bone. It has been observed that presence of surface roughness, at the micrometer and nanometer scales will promote cellular adhesion.2  Furthermore, coating of materials such hydroxyapatite and calcium phosphates on the implant promotes proliferation of osteoblasts.26  Indeed, in studies conducted on titanium implants, surface modification has been observed to enhance bone-implant contact and interfacial bonding to the bone.27  Although a number of modifications of PEEK implants have been described in the literature,28,29  very few studies have compared the osseointegration and bioactivity of PEEK implants with titanium.

Sagomonyants et al15  cultured osteoblasts cells, isolated from surgery patients, on the surface of PEEK and titanium implants and then compared cellular proliferation and activity on both implant materials. It was observed that PEEK stimulated proliferation of osteoblasts, mRNA synthesis, and collagen I turnover comparable to those on smooth and rough titanium. This suggested that carbon fiber reinforced PEEK (CFR-PEEK) and titanium stimulated cellular differentiation and proliferation in comparable magnitude. In contrast to a later study by Sagomonyants et al, in vitro studies failed to observe any similarities between the bioactivity of PEEK and titanium. In a series of studies by Olivares-Navarrete et al,16,18,19  results indicated that although PEEK did stimulate cellular proliferation, the cells proliferating on PEEK were less osteoconductive than those on titanium.16  As suggested by the increased bone-morphogenetic proteins (BMPs) released by MG63-cells, titanium stimulates a more mature cell growth. Indeed, BMPs have been viewed as indicative of increase bone formation and have been used in regenerative medicine for bone regeneration.30  Formation of new blood vessels (angiogenesis) is important for bone regeneration and successful osseointegration.31 

Olivares-Navarrete et al also observed increased expressions of endothelial growth factor A, angiopoietin-1, and fibroblast growth factor 2 from cells cultured on titanium as compared to those growing on PEEK.18  Moreover, they observed that PEEK stimulated a more inflammatory proliferation of cells when compared to titanium. Increased levels of pro-inflammatory interleukins and proapoptic mRNA produced from cells cultured on PEEK indicated a more fibrotic interaction between the polymer and bone.19  That said, titanium was observed to promote a cellular response that is more favorable for bone formation. Proteomic analysis conducted by Zhao et al20  indicated that PEEK favors lesser production of pro-osteoblast proteins than titanium, further strengthening the notion that PEEK is less osseoconductive than titanium.

The results from animal studies support those obtained from the aforementioned in vitro studies. In all the studies, lesser bone-implant contact was observed around PEEK than around titanium implants.2224  When Koch et al compared the osseointegration of titanium, coated and uncoated zirconia, and PEEK implants, significantly lesser bone-implant contact was observed around PEEK implants.24  Similar observations were made by Webster et al, who observed a significantly higher susceptibility of bacterial grown on PEEK implant surfaces, which may be an additional factor playing a role against diminished osseointegration of PEEK implants.22  However, more bacterial studies are needed to further investigate this hypothesis. Results from Nakahara et al suggested that the limited osseoconductive properties of PEEK may be overcome by coating it with bioactive materials such as hydroxyapatite.21  Titanium, being metallic with a very high melting temperature, can be sprayed using high-temperature process without degradation of its surface and structure. Unlike titanium, PEEK is a polymer with a low melting point and, therefore, processes such as plasma spraying and acid-etching may have a detrimental effect on the surface and bulk mechanical properties.32  A major cause of concern of uncoated PEEK is its low wettability and, therefore, a high hydrophobicity that may prevent initial cellular adhesion.33  Although several methods have been advocated for modification of PEEK,29  no studies so far have compared the osseointegration of coated and modified PEEK with commercially available titanium implants.

The studies included in this review had a number of limitations: for instance, the in vitro studies were conducted for short durations.15,16,18–20 Results from in vitro tests alone are inadequate to ascertain the safe use of dental implants in the clinical setting, and robust animal studies are required before they be used safely.34  Only 4 animal studies,2124  compared to 5 in vitro studies15,16,1820  were found during the search process, giving us a lack of animal trials comparing osseointegration of PEEK to that of titanium. Furthermore, a number of inadequacies in the study design may have lead to biased outcomes. None of the animal studies included statistically predetermined sample sizes.2124  Moreover, neither protocol of randomization or blinding of animals was described.2124  No studies described any animal subjects lost to the experiments.2124  Future studies should focus on improving the study design to minimize the sources of bias. The majority of animal research conducted has focused on PEEK's application in spine and cranial surgery.7  Indeed, among the studies reviewed, PEEK implants were placed in the mandible in only one study.24  Macroscopic characteristics, such as implant shape and thread geometry, of PEEK and PEEK-based composites should be studied further and compared to currently used titanium implants. Although coated PEEK may prove to be a viable alternative to titanium, more research should be conducted to analyze the PEEK-apatite bonding, as dental implants are known to fail due to delamination of the coating material.2 

Indeed, more studies are warranted to vindicate the use of PEEK in dental implants. There have been published case reports that document failure of uncoated PEEK implants resulting from severe peri-implantitis caused by poor osseointegration.35  Although PEEK dental implants are commercially available (PEEK-Optima and PEEK-Optima HA Enhanced, Invibio, Lancashire, UK), no clinical studies have been conducted to ascertain the clinical efficacy of PEEK dental implants. Therefore, more animal studies and human trials are vital before PEEK, in any form, is to be used as a dental implant material clinically.

Conclusion

Unmodified PEEK is less osseoconductive and bioactive than titanium. Hence, in its unmodified form, PEEK is unsuitable to be used as dental implant. Inadequate osseoconductivity and bioactivity of the dental implant may lead to severe implantitis and implant failure. Therefore, significantly more research and long-term trials focusing on improving bioactivity of PEEK are required before it can be used as dental implant. More comparative animal and clinical studies are warranted to ascertain the potential of PEEK to be a viable alternative to titanium.

Abbreviations

    Abbreviations
     
  • BMPs

    bone-morphogenetic proteins

  •  
  • CFR

    carbon fiber reinforced

  •  
  • PEEK

    polyetheretherketone

References

References
1
Brånemark
P-I.
Osseointegrated implants in the treatment of the edentulous jaw. Experience from a 10-year period
.
Scand J Plast Reconstr Surg
.
1977
;
16
:
1
132
.
2
Le Guéhennec
L,
Soueidan
A,
Layrolle
P,
Amouriq
Y.
Surface treatments of titanium dental implants for rapid osseointegration
.
Dent Mater
.
2007
;
23
:
844
854
.
3
Cabello
G,
Rioboo
M,
Fábrega
JG.
Immediate placement and restoration of implants in the aesthetic zone with a trimodal approach: soft tissue alterations and its relation to gingival biotype
.
Clin Oral Implants Res
.
2013
;
24
:
1094
1100
.
4
Lee
WT,
Koak
JY,
Lim
YJ,
Kim
SK,
Kwon
HB,
Kim
MJ.
Stress shielding and fatigue limits of poly-ether-ether-ketone dental implants
.
J Biomed Mater Res B Appl Biomater
.
2012
;
100
:
1044
1052
.
5
Javed
F,
Al-Hezaimi
K,
Almas
K,
Romanos
GE.
Is titanium sensitivity associated with allergic reactions in patients with dental implants? A systematic review
.
Clin Implant Dent Relat Res
.
2013
;
15
:
47
52
.
6
Lucas
TJ,
Lawson
NC,
Janowski
GM,
Burgess
JO.
Effect of grain size on the monoclinic transformation, hardness, roughness, and modulus of aged partially stabilized zirconia
.
Dent Mater
.
2015
;
31
:
1487
1492
.
7
Kurtz
SM,
Devine
JN.
PEEK biomaterials in trauma, orthopedic, and spinal implants
.
Biomaterials
.
2007
;
28
:
4845
4869
.
8
Altmeyer
J,
dos Santos
JF,
Amancio-Filho
ST.
Effect of the friction riveting process parameters on the joint formation and performance of Ti alloy/short-fibre reinforced polyether ether ketone joints
.
Mater Design
.
2014
;
60
:
164
176
.
9
Scolozzi
P.
Maxillofacial reconstruction using polyetheretherketone patient-specific implants by “mirroring” computational planning
.
Aesthetic Plast Surg
.
2012
;
36
:
660
665
.
10
Camarini
ET,
Tomeh
JK,
Dias
RR,
da Silva
EJ.
Reconstruction of frontal bone using specific implant polyether-ether-ketone
.
J Craniofac Surg
.
2011
;
22
:
2205
2207
.
11
Niu
C-C,
Liao
J-C,
Chen
W-J,
Chen
L-H.
Outcomes of interbody fusion cages used in 1 and 2-levels anterior cervical discectomy and fusion: titanium cages versus polyetheretherketone (PEEK) cages
.
J Spinal Disord Tech
.
2010
;
23
:
310
316
.
12
Stawarczyk
B,
Eichberger
M,
Uhrenbacher
J,
Wimmer
T,
Edelhoff
D,
Schmidlin
PR.
Three-unit reinforced polyetheretherketone composite FDPs: influence of fabrication method on load-bearing capacity and failure types
.
Dent Mater J
.
2015
;
34
:
7
12
.
13
Uhrenbacher
J,
Schmidlin
PR,
Keul
C,
et al.
The effect of surface modification on the retention strength of polyetheretherketone crowns adhesively bonded to dentin abutments
.
J Prosthet Dent
.
2014
;
112
:
1489
1497
.
14
Schwitalla
A,
Müller
W-D.
PEEK dental implants: a review of the literature
.
J Oral Implantol
.
2013
;
39
:
743
749
.
15
Sagomonyants
KB,
Jarman-Smith
ML,
Devine
JN,
Aronow
MS,
Gronowicz
GA.
The in vitro response of human osteoblasts to polyetheretherketone (PEEK) substrates compared to commercially pure titanium
.
Biomaterials
.
2008
;
29
:
1563
1572
.
16
Olivares-Navarrete
R,
Gittens
RA,
Schneider
JM,
et al.
Osteoblasts exhibit a more differentiated phenotype and increased bone morphogenetic protein production on titanium alloy substrates than on poly-ether-ether-ketone
.
Spine J
.
2012
;
12
:
265
272
.
17
Moher
D,
Liberati
A,
Tetzlaff
J,
Altman
DG.
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement
.
Ann Intern Med
.
2009
;
151
:
264
269
.
18
Olivares-Navarrete
R,
Hyzy
SL,
Gittens
RA,
et al.
Rough titanium alloys regulate osteoblast production of angiogenic factors
.
Spine J
.
2013
;
13
:
1563
1570
.
19
Olivares-Navarrete
R,
Hyzy
SL,
Slosar
PJ,
Schneider
JM,
Schwartz
Z,
Boyan
BD.
Implant materials generate different peri-implant inflammatory factors: poly-ether-ether-ketone promotes fibrosis and microtextured titanium promotes osteogenic factors
.
Spine (Phila Pa 1976)
.
2015
;
40
:
399
404
.
20
Zhao
M,
An
M,
Wang
Q,
et al.
Quantitative proteomic analysis of human osteoblast-like MG-63 cells in response to bioinert implant material titanium and polyetheretherketone
.
J Proteomics
.
2012
;
75
:
3560
3573
.
21
Nakahara
I,
Takao
M,
Goto
T,
Ohtsuki
C,
Hibino
S,
Sugano
N.
Interfacial shear strength of bioactive-coated carbon fiber reinforced polyetheretherketone after in vivo implantation
.
J Orthop Res
.
2012
;
30
:
1618
1625
.
22
Webster
TJ,
Patel
AA,
Rahaman
MN,
Sonny Bal B. Anti-infective and osteointegration properties of silicon nitride, poly(ether ether ketone), and titanium implants
.
Acta Biomater
.
2012
;
8
:
4447
4454
.
23
Wu
SH,
Li
Y,
Zhang
YQ,
et al.
Porous titanium-6 aluminum-4 vanadium cage has better osseointegration and less micromotion than a poly-ether-ether-ketone cage in sheep vertebral fusion
.
Artif Organs
.
2013
;
37
:
E191
E201
.
24
Koch
FP,
Weng
D,
Krämer
S,
Biesterfeld
S,
Jahn-Eimermacher
A,
Wagner
W.
Osseointegration of one-piece zirconia implants compared with a titanium implant of identical design: a histomorphometric study in the dog
.
Clin Oral Implants Res
.
2010
;
21
:
350
356
.
25
Esposito
M.
Biological factors contributing to failures of osseointegrated oral implants. (l). Success criteria and epidemiology
.
Eur J Oral Sci
.
1998
;
106
:
527
551
.
26
Ravichandran
R,
Ng
C,
Liao
S,
et al.
Biomimetic surface modification of titanium surfaces for early cell capture by advanced electrospinning
.
Biomed Mater
.
2012
;
7
:
015001
.
27
Scarano
A,
Degidi
M,
Perrotti
V,
Degidi
D,
Piattelli
A,
Iezzi
G.
Experimental evaluation in rabbits of the effects of thread concavities in bone formation with different titanium implant surfaces
.
Clin Oral Implants Res
.
2014
;
16
:
572
581
.
28
Najeeb
S,
Zafar
MS,
Khurshid
Z,
Siddiqui
F.
Applications of polyetheretherketone (PEEK) in oral implantology and prosthodontics
.
J Prosthodont Res
.
2016
;
60
:
12
19
.
29
Najeeb
S,
Khurshid
Z,
Matinlinna
JP,
Siddiqui
F,
Nassani
MZ,
Baroudi
K.
Nanomodified PEEK dental implants: bioactive composites and surface modification—a review
.
Int J Dent
.
2015
;
2015
:
381759
.
30
Lee
D-W,
Yun
Y-P,
Park
K,
Kim
SE.
Gentamicin and bone morphogenic protein-2 (BMP-2)-delivering heparinized-titanium implant with enhanced antibacterial activity and osteointegration
.
Bone
.
2012
;
50
:
974
982
.
31
Abshagen
K,
Schrodi
I,
Gerber
T,
Vollmar
B.
In vivo analysis of biocompatibility and vascularization of the synthetic bone grafting substitute NanoBone
.
J Biomed Mater Res A
.
2009
;
91
:
557
566
.
32
Suska
F,
Omar
O,
Emanuelsson
L,
et al.
Enhancement of CRF-PEEK osseointegration by plasma-sprayed hydroxyapatite: a rabbit model
.
J Biomater Appl
.
2014
;
29
:
234
242
.
33
Waser-Althaus
J,
Salamon
A,
Waser
M,
et al.
Differentiation of human mesenchymal stem cells on plasma-treated polyetheretherketone
.
J Mater Sci Mater Med
.
2014
;
25
:
515
525
.
34
Pearce
AI,
Richards
RG,
Milz
S,
et al.
Animal models for implant biomaterial research in bone: a review
.
Eur Cell Mater
.
2007
;
13
:
1
10
.
35
Khonsari
RH,
Berthier
P,
Rouillon
T,
Perrin
J-P,
Corre
P.
Severe infectious complications after PEEK-derived implant placement: report of three cases
.
J Oral Maxillofac Surg Med Pathol
.
2014
;
26
:
477
482
.