DOI: 10.1111/prd.
12280
REVIEW ARTICLE
Biofilm as a risk factor in implant treatment
Diane M. Daubert | Bradley F. Weinstein
Department of Periodontics, University of Washington, Seattle, Washington, USA
Correspondence
Diane M. Daubert, Department of Periodontics, University of Washington, Seattle, WA, USA.
Email: ddaubert@uw.edu
1 |  I NTRO D U C TI O N
Dental implants are highly successful at replacing missing teeth and
restoring oral health-­related quality of life. Despite a high rate of suc-
cess, however, there remains a significant number of patients who
develop peri-­implant mucositis and peri-­implantitis.1-6 The definition
of success for implants extends beyond merely implant survival;7 in
addition to lack of mobility, ‘success’ encompasses the maintenance
of health of the peri-­implant tissues despite the constant microbial
challenge in the oral environment.
While peri-­implantitis is a complex disease with multiple risk fac-
tors, it is generally accepted that the initiation of peri-­implant disease
results from a bacterial challenge and excessive host response.8,9
Dental implants are placed in an oral microbial environment of com-
mensal bacteria, and potentially pathogenic microorganisms, or
pathobionts.10 Much investigative effort has gone into the study of
the peri-­implant biofilm, its relationship to periodontal biofilm, and
the clustering of bacteria in states of health and disease. Despite
these efforts, there is no clear consensus for a specific bacterial
complex that initiates peri-­implant bone loss.11 In periodontitis, a
12
keystone pathogen present in low abundance has been identified
that is able to disrupt the periodontal microbiota and lead to dys-
biosis. The identification of such a keystone microorganism in the
peri-­implant microbial community remains elusive.
There is a wealth of information ranging from data on early
colonization, longitudinal changes in the peri-­implant biofilm, com-
parison of peri-­
implant biofilm with periodontal biofilm, differ-
ences in biofilm by implant surface and type, to biofilm changes in
states of implant health and disease. In a leap akin to the first use
of a microscope, the advent of open-­ended, culture-­free sequenc-
ing techniques allow a much richer picture of the peri-­implant bio-
film including previously unculturable and/or unknown species. The
results of sequencing data suggest that the periodontal and peri-­
implant microbiomes are less similar than previously thought and in-
13
deed represent unique niches in the oral cavity. In addition, there
is emerging evidence of the interplay between the titanium surface
Periodontology 2000. 2019;81:29–40. wileyonlinelibrary.com/journal/prd   © 2019 John Wiley & Sons A/S. |  29
and peri-­implant biofilm, which may provide insight into the patho-
genesis of peri-­implant disease.14-17
The aim of this article was to summarize the microbiological find-
ings at dental implants, the interaction of oral biofilm that is specific
to dental implants, and what is known regarding biofilm as a risk
factor for specific stages of implant treatment. Appropriate biofilm
management is a key part of the armamentarium in the prevention
and treatment of peri-­implant diseases.
2 | PE R I - ­I M PL A NT B I O FI LM
The pace of advancement in microbiological techniques and bioinfor-
matics has been tremendous. Each year, the ability to capture more
in-­depth information has increased, making it difficult to compare
studies. When assessing the presence of oral taxa with culture or
molecular techniques, only part of the biofilm data is available, and
conclusions may be misinterpreted. Nevertheless, it is valuable to
review what has been discovered regarding the biofilm in the follow-
ing specific scenarios: initial formation, mature peri-­implant biofilm,
peri-­implant biofilm in the edentulous patient, and biofilm associ-
ated with peri-­implant health and disease. Much can be learned from
a synopsis of key findings that created the groundwork for clinical
care and subsequent research. Following this, a discussion of find-
ings using open-­ended techniques is presented. Prior interpretations
may need to be re-­evaluated with open-­ended sequencing.
3 | I N ITI A L B I O FI LM FO R M ATI O N
Implants have a supra-­and submucosal region exposed to the oral
environment. Biofilm formation on implants may be dissimilar to
teeth because of chemical and physical surface properties of the
implant on which the biofilm is established.18 Bacterial adhesion
on titanium is affected by surface roughness, free energy, chem-
istry, and titanium purity.19 In vivo models using titanium disks
Published by John Wiley & Sons Ltd
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30       DAUBERT and WEINSTEIN
inserted into acrylic splints have been used to assess the influ-
ence of surface characteristics on initial biofilm formation. John
et al. reported that in healthy subjects, machine-­m odified acid-­
etched surfaces had slower formation vs. acid-­etched sandblasted
large grit, acid-­etched surface, or machined surface. 20 Ribeiro
et al. also assessed surface treatments including machined pure
titanium, acid-­etched titanium, and anodized and laser-­irradiated
disks in healthy subjects, and conversely did not find significant
differences in total bacteria and Streptococcus oralis by surface
21
treatment. The studies are difficult to compare, as the surface
treatments were not equivalent in the 2 studies. Another group
looked at biofilm formation on titanium with different surface
treatments. They found that the composition and proportion of
initial colonizers were influenced by the periodontal status more
than by the surface characteristics. 22 While the model of titanium
disks in a splint does not replicate an implant inserted into bone
and surrounded by epithelium, these studies shed light on the
complexity that includes not only titanium surface and oral micro-
biome but also the periodontal status of the patient.
Biofilm formation has also been assessed on ceramic sur-
faces in comparison with titanium and found to be similar in ini-
tial formation both in vitro and in vivo. Al-­A hmad et al. assessed
biofilm formation in vivo on machined titanium, modified tita-
nium, modified zirconia, machined alumina-­toughened zirconia,
sandblasted alumina-­toughened zirconia, and machined zirconia.
They determined that after 3 and 5 days there were no signifi-
cant differences in biofilm composition on the implant surfaces. 23
Subsequent evaluation of initial biofilm formation on titanium
and ceramic surfaces with low surface roughness similarly found
no significant differences in initial adhesion or biofilm thickness
between the titanium and ceramic surfaces. 24 Periodontal patho-
gens in culture were found to have similar adherence on polished
tetragonal zirconia polycrystal disks vs. polished titanium disks. 25
These findings do not indicate superiority of ceramic or titanium
in the inhibition of bacterial adherence. While the majority of im-
plants are titanium, peri-­implantitis has been reported with zirco-
nia implants. 26
Initial bacterial colonization of dental implants happens
quickly in the oral cavity for both dentate and fully edentulous
patients. 27,28 Fürst et al. assessed this in periodontally healthy
patients up to 12 weeks postimplant placement. Biofilm samples
were collected from 14 subjects and DNA checkerboard analysis
was utilized to report on 40 known bacterial species, and was
then compared with bacteria at adjacent tooth sites. All subjects
had low initial plaque scores. Biofilm formation occurred within
29
30 minutes of implant placement in the oral cavity. Between
30 minutes and 1 week, only Veillonella parvula had higher bac-
terial loads at implant sites compared with adjacent teeth. At
12 weeks the species remained similar but the bacterial load was
higher at tooth sites compared with implant sites. Thus, while
preexisting species may colonize an implant rapidly, a distinction
in microbial load is apparent between the tooth and peri-­implant
niche.
4 | M AT U R E PE R I - ­I M PL A NT B I O FI LM
Agerbaek et al. compared patterns of 40 bacterial strains using DNA-­
DNA hybridization in subjects with dental implants and compared
species found at tooth and implant sites including probing depth as a
covariate. They found similar microbial findings at tooth and implant
sites, but the percentage of positive sites for Aggregatibacter ac-
tinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia,
and Treponema denticola was lower at implant sites with probing
depth ≥ 5 mm vs. tooth sites ≥ 5 mm, and tooth sites with prob-
ing depth ≥ 4 mm had a 3.1-­fold higher bacterial load than implant
sites.30 The difference in findings may indicate that sites with deeper
probings around implants may be related to implant diameter and
crown contour or depth of placement (around implants without plat-
form switching), and may not be associated with peri-­implant disease
in the absence of bone loss and bleeding.
It is well established that periodontal disease is a risk factor
for peri-­implantitis.3,31-33 Quirynen et al. examined biofilm in pa-
tients with a diagnosis of periodontal disease: 42 partially edentu-
lous patients with gingivitis or mild to moderate periodontitis were
examined, and biofilm samples were collected and analyzed using
DNA-­DNA hybridization, culture, or PCR techniques from 1 week
postabutment insertion to 18 months. 27 At 7 days, the species
were nearly identical among peri-­implant sites and tooth sites. A
complex microbiota was found at implant sites within 2 weeks, and
the similarity continued between tooth and implant sites through
18 months. Because the analysis did not utilize open-­ended micro-
bial analysis, the similarity between tooth and implant sites only ap-
plies to the specific species studied, and a broader survey may better
describe any differences. Although this study suggests transmission
of bacteria from periodontally involved teeth to implants, it cannot
be concluded that those species cause peri-­implant disease because
the selective assessment of a limited number of species is biased
towards positive associations which are false.
5 | B I O FI LM A S S O C I ATE D W ITH PE R I -­
I M PL A NT H E A LTH VS . D I S E A S E
Healthy implants have been characterized as being colonized pre-
dominately by gram-­positive rods and cocci in a manner similar to
healthy teeth. 29 In contrast to the biofilm found at healthy implants,
the microbiome at sites of peri-­implant disease has generally been
described as similar to that associated with chronic periodontitis,
with severe peri-­implantitis characterized as a polymicrobial anaero-
bic infection with increased numbers of aerobic gram-­negative ba-
cilli.34 Not all cases of peri-­implantitis fit this pattern, however. The
peri-­implantitis microbiome may occasionally be linked to a different
microbiome including peptostreptococci or staphylococci, or biofilm
associated with implanted medical devices.35
Persson and Renvert used DNA-­DNA checkerboard to analyze
the presence of 78 bacterial species in the biofilm of 166 implants
with peri-­implantitis and 47 healthy implants. Of the 78 species, 19
DAUBERT and WEINSTEIN
were found at higher counts at implants with peri-­implantitis com-
pared with the healthy implants. In their study, a cluster of bacteria
including P. gingivalis, Staphylococcus aureus, S. anaerobius, S. inter-
medius, S. mitis, T. forsythia, and T. socranskii were found to be asso-
ciated with peri-­implantitis.36 In contrast to chronic periodontitis,
this cluster of bacteria continues to elucidate the differences in the
disease entities.
A further attempt to characterize the biofilm in periodontal and
peri-­implant health and disease provides some additional insight.
Zhuang et al. assessed 22 subjects with a healthy and diseased im-
plant, and a site with healthy gingiva and periodontitis, in order to
quantify 6 pathogens. While the detection frequencies were higher
at diseased tooth and implant sites vs. healthy sites within the same
subject, the putative pathogens were found at all sites regard-
less of health status. In this patient group, P. gingivalis, along with
Fusobacterium nucleatum, were not associated with peri-­implantitis.37
Another difference in the peri-­implant niche besides the titanium
surface is the implant-­abutment connection. Canullo et al. compared
the microbiologic findings of 10 green, orange, and red complex
species in samples collected from the peri-­implant sulcus inside the
implant connection, and from the sulcus of the adjacent teeth of pa-
tients with healthy implants in periodontal health to implants with
peri-­implantitis. All 10 species were found in the peri-­implant sulcus
of both groups. Orange complex species were the most prevalent in
both groups, but were lower in the healthy group. The only signifi-
cant differences in prevalence between the groups were observed
for Tanerella denticola and Eikenella corrodens, which were lower in
the healthy group. The most significant differences between groups
were found inside the peri-­implant connection, where P. gingivalis,
T. forsythia, P. intermedia, Campylobacter rectus and E. corrodens had
significantly lower prevalence in the healthy group.38 While the re-
sults may be limited by the microbiological techniques utilized and
the lack of periodontal diagnosis for the peri-­implantitis group, they
highlight the complexity of the peri-­implant niche.
6 | B I O FI LM FI N D I N G S I N TH E FU LLY
E D E NT U LO U S PATI E NT
Edentulous patients lack teeth to retain periodontal pathogens.
However, edentulous patients do not have a lower risk of developing
peri-­implantitis. This can be explained by data suggesting that peri-
odontal pathogens can reside in the buccal cheek cells of edentulous
patients.39,40 In a case report, a subject with aggressive periodontitis
who underwent full mouth extractions prior to implant placement
had an almost identical spectrum of pathogens 6-­8 months after
41
implant placement, and subsequently developed peri-­implantitis.
A review of biofilm findings at implants in edentulous patients may
provide further clues regarding the distinct dental implant submu-
cosal niche.
Early colonization of dental implants in edentulous patients was
assessed by culture technique 2-­10 weeks after implant placement
and compared with biofilm present before insertion. Gram-­positive
|
      31
cocci and rods dominated the supragingival plaque on the implants,
and the subgingival plaque was dominated by Haemophilus species
and V. parvula. In addition, the resulting data identified a group of
bacteria that was specifically related to the implants and was not
found in the edentulous patients, and which included Actinomyces
odontolyticus, Peptostreptococcus micros, Haemophilus tigena, and
Leptrotrichis buccalis. Periodontal pathogens were not identified
prior to implant placement, but were found at 10 weeks postplace-
ment, suggesting that they were dependent on the niche created in
the peri-­implant sulcus.42
In contrast, a later group used culture method and enzyme elec-
trophoresis to evaluate the biofilm from 91 implants in 20 eden-
tulous subjects with a past history of periodontitis. They found
the biofilm of these subjects to be associated with that found in a
healthy periodontium or gingivitis, and that A. actinomycetemcomi-
tans and P. gingivalis were not detected. Sulcus depth at the implants
did affect the biofilm as P. intermedia was only detected in subjects
with a probing depth of ≥ 5 mm.43
More recently, molecular methods were used to assess the
presence of P. gingivalis, T. forsythia, and S. aureus in 26 edentulous
patients. A quantitative reverse transcription-­PCR assay for the 3
species was below the detection limit prior to placement and also at
6 months postplacement.44 Although limited in the scope of bacte-
rial findings, this is additional evidence that the peri-­implant sulcus
may be a unique niche.
7 | O PE N - ­E N D E D S EQ U E N C I N G
M I C RO B I A L C H A R AC TE R IZ ATI O N
Culture and molecular methods have specific bacterial targets,
which provide valuable information regarding known pathogens but
limit data of unknown and unculturable species. Considering that
more than 500 distinct oral taxa may be inhabiting oral surfaces, the
selective assessment of a small number of these is biased towards
positive associations which may be false. Existing studies utilizing
targeted bacterial identification studies should always be cautiously
interpreted. Species identified are essentially ‘cherry-­picked’ and
can only be considered as markers of microbiome transitions. On
the other hand, metagenomics gives a much broader picture of the
peri-­implant biofilm. Specifically, 16S rRNA technology allows for
an open-­ended exploration of the microbial composition of dental
implants. Biofilm findings at healthy and diseased sites have been
re-­evaluated and the findings follow below.
The first report of implant biofilm using 16S sRNA technology was
published in 2010.45 Subsequent studies have reported additional
information providing a wealth of data pertaining to the differences
between healthy and diseased implants and teeth.13,46-53 It remains
difficult to compare studies as there is a lack of consensus regarding
case selection and definitions, including definitions of periodonti-
tis and peri-­implantitis. In some cases the periodontal status of the
patient, which is regarded as a risk factor for peri-­implantitis, is not
reported. There is additional variability in the clinical parameters of
 |
32       DAUBERT and WEINSTEIN
the patients and of the implants and teeth sampled, including inclu-
sion or exclusion of smokers in some, or exclusion of patients with
periodontal disease in others. In addition, sampling methods vary,
which may affect the outcomes. In a short period of time, the pace
of innovation has led to the discontinuation of the first generation
sequencing instrument (introduced in 2005), and the advent of new
instruments that may provide 10-­fold more reads. Finally, the pipe-
lines used for analysis of the data have made advances, also making
it difficult to compare studies.
Koyanagi et al. collected submucosal biofilm samples from 3 sub-
jects with a healthy implant, an implant with peri-­implantitis, and a
periodontally diseased tooth, and compared the microbial profiles.
They concluded that the peri-­implant biofilm was more complex than
either a periodontally healthy tooth or periodontitis. They reported
a low prevalence of common periodontal pathogens in the peri-­
implant biofilm. The phyla Chloroflexi, Tenericutes, and Synegistetes,
and several species were only detected at implant sites.45 This study
provides additional insight but is limited by the small sample size, and
thus it is difficult to draw any conclusions.
In 2012, Kumar et al. utilized 16S pyrosequencing to assess the
subgingival biofilm of 40 subjects with periodontitis, peri-­implantitis,
or periodontal and peri-­implant health. Specific bacteria were found
to be associated with each group. Several species were found to be
unique to the peri-­implant niche. The authors concluded that the
peri-­implant microbial community is significantly different from the
periodontal microbial community and is less complex than periodon-
titis, and that there may be a different mechanism for the pathogen-
esis of peri-­implantitis.46 This contradiction in microbial complexity
may be a result of a larger sample, but may also be confounded by
the fact that the current periodontal status of the implant patients
was not included in the analysis.
Koyanagi et al. expanded on their existing data and included an
additional 3 subjects, in whom they assessed the differences be-
tween peri-­implantitis biofilm and periodontal microbiome in sub-
jects with periodontitis. The peri-­implant composition was more
complex when compared with the periodontal sites. The preva-
lence of periodontal pathogenic bacteria was not high at implant
47
sites.
In 2013, Dabdoub et al. reported on a much larger group of 81
patients in a study evaluating the microbiome of implants and adja-
cent teeth. They assessed 4 separate groups: healthy teeth/healthy
implants, diseased teeth/healthy implants, healthy teeth/diseased
implants, and both diseased. The percentage of shared species was
evaluated using deep sequencing to determine the degree of similar-
ity between the pairs; 523 species were identified and the resulting
analysis led to the delineation of 2 distinct ecosystems at teeth and
implants, bringing into question the earlier hypothesis that teeth are
a microbial reservoir for implants.13
Using 16S rDNA sequences and anaerobic culture technique,
Tamura et al. evaluated submucosal bacterial specimens from 30
patients and distinguished 20 genera at healthy implant sites and
31 genera at sites of peri-­implantitis.48 The peri-­implantitis sites
had a 10-­
fold higher number of colony-­
forming units than the
healthy implant sites. The authors concluded that the conventional
periodontal pathogens were not the only species active in peri-­
implantitis and that asaccharolytic anaerobic gram-­positive rods may
play an important role. They did not report the periodontal status of
the patients in each of the groups.
Another group assessed the periodontal and peri-­implant mi-
crobiome in 7 patients with both generalized periodontitis and peri-­
implantitis, and found no distinction in the biofilm between the teeth
and implants in the same subjects. They found the most abundant
genera on implants were Rothia, Streptoccaceae, and Porphyromonas.
The lack of distinction in the biofilm between teeth and diseased
implants within the same patient suggests that other factors in ad-
dition to biofilm composition may account for the distinct pathology
between peri-­implantitis and periodontitis.49
Periodontal disease is a risk factor for peri-­implantitis; however,
healthy patients may also develop peri-­implant disease. Da Silva et al.
evaluated microbial diversity at 20 implants with peri-­implantitis
compared with healthy implants, excluding patients with periodonti-
tis, and those who reported smoking. They reported marked differ-
ences in the composition of subgingival biofilm between the healthy
implants and implants with peri-­implantitis, and also reported more
orange complex periodontal pathogens present at sites of peri-­
implantitis compared with implant health.50
In 2015, Zheng et al. utilized 16S rRNA analysis to assess 24 pa-
tients, 10 with healthy implants, 8 with mucositis, and 6 with im-
plants with peri-­implantitis. They did not report on the periodontal
diagnosis of the patients, but were the only group to report on mu-
cositis findings using 16S sRNA analysis. They concluded that the
microbial communities of peri-­implant mucositis were intermediate
in nature between those of healthy implants and implants with peri-­
implantitis, and that periodontal pathogens play a role in shifting
from health to disease at implant sites.51
More recently, peri-­
implantitis sites were compared with
pooled samples from healthy teeth in patients with a history of
periodontal disease. All patients were nonsmokers and lacked reg-
ular maintenance. They found distinctions in the biofilm at teeth
and diseased implants within subjects. More diversity was found
at the healthy tooth sites compared with the peri-­implantitis sites,
and while principal component analysis showed some distinction
between the groups, there remained overlap. 52 Another group as-
sessed the microbiome at 1 implant in 82 patients and compared
peri-­implantitis sites with healthy implants, finding distinctions
between health and disease at all taxonomic levels. 53
Culture and molecular methods allow the researcher to look
for specific pathogens, which requires a species-­specific hypothe-
sis. The benefit of using open-­ended sequencing is that all species
are detected, allowing a true evaluation of the biofilm and a much
broader picture that is not dependent on a targeted approach. In
order to best utilize open-­ended data related to peri-­implant health
and disease, it would be useful to have a consensus of case defi-
nitions, an understanding of confounding factors, and a minimum
sample size. A recent systematic review of the microbial profile as-
sociated with dental implants confirms that the lack of homogeneity
DAUBERT and WEINSTEIN
of the reviewed studies did not allow for any direct comparison. 54
Thus, while the microbial profile has been mapped for periodonti-
tis, it has not been accomplished for peri-­implantitis. 55
It would be of interest to re-­evaluate early colonization compared
with mature biofilm along with probing depth as a co-­factor in implant
biofilm utilizing deep sequencing. The search will continue to identify
parameters that affect the peri-­implant microbiome and implant health.
8 | I NTE R AC TI O N B E T W E E N B I O FI LM
A N D TITA N I U M
The presence of titanium in the oral cavity may be involved in the initia-
tion and progression of peri-­implant disease.54 In a review of epidemiol-
ogy of peri-­implant disease, titanium corrosion was suggested to have
2
relevance for later peri-­implant bone loss. Dental implants have a surface
coating of titanium dioxide that is responsible for the biocompatibility of
titanium implants.56 This surface coating can be weakened or disrupted,
56
leading to titanium corrosion. It has been shown that oral bacterial taxa
are capable of affecting titanium electro-­conductive properties, and can
lead to spontaneous generation of electricity and corrosion of titanium
15
implants. Streptococcus mutans has been shown to increase the corro-
sion current57 and to induce titanium corrosion.14 A recent case control
study by Safioti et al. with peri-­implantitis and healthy controls found an
8-­fold increase in titanium corrosion products in the plaque around im-
17
plants with peri-­implantitis compared with healthy ones. In addition,
when assessing the potential effects of titanium products on the peri-im-
plant microbiome using 16S rRNA analysis, titanium dissolution products
have been shown to act as a modifier of the peri-implant microbiome
structure.58 These data support the utilization of treatment methods
that prevent disruption of the titanium oxide surface.
9 | TR E ATM E NT U S E D FO R I M PL A NT
B I O FI LM R E D U C TI O N
Biofilm reduction is a hallmark of periodontal treatment. The com-
mon finding of biofilm in both periodontitis and peri-­
implantitis
has erroneously led to the direct transfer of periodontitis proto-
cols to form the basis for treating peri-­implant mucositis and peri-­
implantitis. The removal of bacteria alone may not be sufficient for
peri-­implantitis treatment59 and common antimicrobial agents may
compromise the viability of the titanium surface.60 The remainder
of this paper will review the evidence for treatment used to control
implant biofilm at all stages of implant treatment: preoperatively, in-
traoperatively, postoperatively, and during long-­term maintenance.
10  | PR EO PE R ATI V E B I O FI LM R E D U C TI O N
The main preoperative biofilm reduction approaches that have been
studied are the administration of antibiotics and the use of chlorhex-
idine rinses. While there may be other preoperative interventions,
|
      33
such as scaling and root planing and oral hygiene instruction, which
may help reduce biofilm levels, they have not been studied in regard
to their effects on implant success rates.
A Cochrane review of antibiotic usage with implant placement
showed a slight benefit to success rates when a 1-­time dose of antibiot-
ics was administered 1 hour prior to implant placement.61 There was no
significant benefit with postoperative antibiotics. A more recent sys-
tematic review by Chrcanovic et al. found that prophylactic antibiotics
do reduce implant failures, but that 50 patients must be given prophy-
lactic antibiotics to prevent 1 failure.62 The most common preoperative
antibiotic studied was Amoxicillin in a 2 g dosage.
Preoperative chlorhexidine has been evaluated for its effects
on implant failure rate and infection-­r elated complications. It has
been shown to reduce salivary bacterial levels 5 minutes after ad-
ministration. 63 A classic study by Löe and Schiott demonstrated
that twice daily use of 0.2% chlorhexidine effectively prevented
plaque formation in dental students. 64 It does not appear to mat-
ter whether the chlorhexidine contains alcohol or not. 65 A surgical
study evaluated the amount of bacteria in bone harvested during
implant surgery when 0.1% chlorhexidine was utilized as an im-
mediate presurgical rinse compared with sterile water. Bone from
the chlorhexidine group contained significantly fewer organisms
present vs. the control group. 66 A large retrospective study of
2,641 implants demonstrated that chlorhexidine use periopera-
tively reduced infectious complications from 8.7% to 4.1%, and
that implants which experienced an infectious complication had
a 6-­f old higher failure rate (12% vs. 2%).67 The reduction in oral
bacterial counts from chlorhexidine rinses pre-­and postopera-
tively appears to reduce the rate of implant failure and complica-
tions although exact protocols vary widely from study to study.
11 | TH E RO LE A N D TR E ATM E NT O F
B I O FI LM I N PE R I - ­I M PL A NT M U COS ITI S
Peri-­implant mucositis appears to be reversible with nonsurgical me-
chanical debridement and proper oral hygiene.68 (Figure 1). However,
once bone loss takes place, and an implant has peri-­implantitis, non-
surgical therapy no longer has significant benefit.69 The evidence
supports a strong and causal link between excessive plaque and
peri-­implant mucositis.70 Experimental studies in dogs and humans
have shown that as plaque increases, gingival inflammation at im-
plants increases simultaneously. Ericsson et al. allowed nonplatform
switched implants in beagle dogs to accumulate plaque for 90 days.
Histology revealed an inflammatory cell infiltrate around the im-
plants that was similar to that around teeth with gingivitis, but which
extended more apically (towards alveolar bone) than that found in
gingivitis.71 Abrahamson showed similar results after 5 months with-
out plaque control although the zone of inflammatory infiltrate was
larger after this period of time. In addition, Abrahamson reported on
a zone of inflammatory infiltrate at the implant-­abutment junction
which, it was speculated, was a result of bacterial contamination at
this interface.72 Zitzmann et al. evaluated implants in humans that
 |
34       DAUBERT and WEINSTEIN
F I G U R E   1   Poor oral hygiene associated with peri-­implant
mucositis
were permitted to accumulate plaque for 3 weeks.73 The authors
found a direct correlation between the plaque index and gingival
index around implants, suggesting that inflammation increases with
escalations in plaque levels. Soft tissue biopsies performed before
and after the plaque accumulation phase showed an increase in in-
flammatory infiltrates throughout the tissues adjacent to the plaque-­
covered implants. Romanos et al. demonstrated a greater tendency
towards periodontal pathogen accumulation at implants with a butt-­
joint connection than at Morse taper connection implants.74
Because it is believed that peri-­
implant mucositis precedes
peri-­implantitis,75 efforts to reduce peri-­
implant mucositis have
the potential to reduce peri-­implantitis. Decisions about the proper
interval, approach, and instrumentation used for peri-­implant mu-
cositis prevention have recently been discussed in clinical practice
guidelines for practitioners.76 Findings from the associated system-
atic review suggest that a dentifrice containing triclosan may be
beneficial. The authors found no difference between manual and
electric toothbrushes. They recommended that professional clean-
ings of implant prostheses be completed every 6 months at mini-
mum due to the rebound of bacterial levels, and they suggested the
use of glycine powder abrasion at each visit rather than plastic cu-
rettes.77 Proper use of air polishing is important to minimize the risk
of air emphysema, of which 9 cases were reported between 1997
and 2001, each of which concluded uneventfully.78 It has been es-
timated that the risk of an air-­emphysema following glycine powder
79
air polishing is approximately 1 in 666,666.
These regular maintenance visits form the mainstay of treat-
ment to prevent the transition from peri-­implant mucositis to peri-­
implantitis. In a 5-­year retrospective study, Costa et al. found that
individuals diagnosed with peri-­
implant mucositis who returned
for yearly maintenance visits had a significantly lower rate of peri-­
implantitis (18.0%) compared with those who did not have regular
periodontal maintenance (43.9%).80 Regular maintenance has been
shown to be effective in maintaining implants in subjects with ag-
gressive periodontal disease. A cohort of 5 periodontally healthy
patients and 5 patients with aggressive periodontal disease were fol-
lowed for 10 years after implant placement in a prospective study to
F I G U R E   2   Maintenance therapy after implant placement
reduced the failure rate by 80% (P < 0.001) 82
determine the effect of periodontal disease on microbiological and
periodontal outcomes of the implant treatment.81 The nonretainable
teeth were extracted and the patients had maintenance visits every
3 months for 10 years. Clinical and radiographic examinations were
performed during the 10 years along with microbial examinations
with dark-­field microscopy. While the probing depth on teeth was
greater and the gingival index higher in the aggressive periodontitis
group vs. the healthy group, the plaque index and probing depth on
implants were comparable. They concluded that patients with ag-
gressive periodontitis can be treated successfully with implants but
the attachment loss may be greater over time. Additionally, lack of
regular maintenance has been recently associated with an increase
in implant failure (Figure 2).82
There has been some controversy regarding the best method
for reducing biofilm on an exposed implant surface. Because of con-
cerns about damage to the implant surface, curettes made of many
softer materials have been developed, and air powder polishing has
received considerable attention with various powders developed to
disrupt the biofilm from an implant surface. In addition, multiple top-
ical antimicrobials have been proposed for reducing biofilm on an
implant surface. Yet each modality is not without its negative side
effects.60,83,84
For instance, plastic curettes have been shown to leave behind
plastic debris on implant surfaces in approximately 10%-­
20% of
cases, which can be difficult to remove.83 Steel curettes and ultra-
sonic tips can leave behind surface alterations on implants, which
may encourage further bacterial colonization of previously smooth
surfaces.84 Also, recent in vitro evidence from Kotsakis et al. sug-
gests that the topical antimicrobials can affect implant surfaces by
leaving behind residues that are cytotoxic.60 In this study, chlor-
hexidine, NaOCl-­ethylene diamine tetraacetic acid, and citric acid
were compared with sterile saline. The test groups showed better
reduction of bacteria compared with the saline, but they altered the
implant surface in ways that negatively affected nearby osteoblasts,
with chlorhexidine having the most cytotoxic effect.
As for mechanical debridement efficacy, a number of studies
have found air polishing to be more effective than curettes, ultra-
sonics, and lasers for subgingival implant surface debridement, and
DAUBERT and WEINSTEIN
to cause less damage to the implant surface. 84-86 Polishing with
glycine powder is thought to be less damaging to implant surfaces
than sodium bicarbonate. 87 A study of 6 months duration compared
glycine powder polishing with manual scaling using a plastic curette
and chlorhexidine for the treatment of peri-­implant mucositis. 88
The authors found that glycine powder polishing was more effec-
tive at reducing plaque levels and probing depths, and was equally
as effective as manual scaling at reducing bleeding. Schwarz et al.
evaluated air polishing in a systematic review and concluded that
the evidence did not support its superiority for treatment of peri-­
implant mucositis, but that signs of inflammation were significantly
reduced in the nonsurgical treatment of peri-­implantitis. 89
Other treatment approaches that have been proposed for reduc-
ing peri-­implant mucositis include administration of systemic and
local antibiotics, laser therapy, photodynamic therapy, and meticu-
lous oral hygiene. The evidence for systemic antibiotics to reverse
peri-­implant mucositis is scant. A review of the subject found no
significant benefit to either locally or systemically delivered antimi-
90
crobials. Muthukuru et al. evaluated local antibiotics, specifically
minocycline, chlorhexidine, and doxycycline, and found them to
be effective at reducing bleeding on probing (BOP) at 6 months in
patients with peri-­implant mucositis. With repeated application, re-
sults could be maintained for 12 months.91
Meticulous oral hygiene has been shown to reduce plaque at
implants and thereby reduce peri-­implant mucositis. In a small, pro-
spective study, Salvi et al. recreated the classic experimental gingivi-
tis study around dental implants. After 3 weeks without oral hygiene
the gingival index around implants increased by more than the gingi-
val index around teeth. Reinstitution of oral hygiene, which reduced
the plaque index to 0 in the group, led to resolution of the inflamma-
tion at both implants and teeth.68
12 | TH E RO LE A N D TR E ATM E NT O F
B I O FI LM I N PE R I - ­I M PL A NTITI S
Once an implant has peri-­implantitis, treatment efforts focused on
biofilm remain an important standard part of therapy. Peri-­implantitis
defects may progress rapidly and in a more aggressive manner than
that observed in a periodontitis. An example is shown demonstrat-
ing such rapid progression in a nonsmoking patient with no prior
health concerns who had a history of periodontal disease (Figure 3).
The ­patient had 3 implants placed in the right and left mandibular
posterior sextants and over a period of 5 years lost significant bone.
Surgical and nonsurgical intervention did not stop the progression
and the disease progression ultimately resulted in explantation of all
6 implants (Figure 3).
Renvert et al. reviewed nonsurgical treatment options for
peri-­implantitis in 2008. They included mechanical debridement
with and without local and systemic antibiotics, and laser ther-
apy. The authors concluded that mechanical therapy alone was
not effective in treating peri-­implantitis. Mechanical therapy plus
local or systemic antibiotics helped to reduce bleeding on probing
|
      35
and probing depths, but was unable to effectively treat peri-­
implantitis. Lasers were shown to provide no more benefit than
mechanical therapy. 69
Laser therapy and photodynamic therapy were further evaluated
in a systematic review for their effects on peri-­implantitis. The re-
sults suggest that laser treatment may be effective in the short term
(6 months) at reducing signs of peri-­implant mucositis such as bleeding
on probing, but that neither laser therapy nor photodynamic ther-
apy was effective at increasing clinical attachment level (CAL) peri-­
implantitis.92 A prospective study performed on zirconium implants
compared mechanical therapy and chlorhexidine with laser therapy
using the erbium-­doped yttrium aluminium garnet laser. The authors
found 52.9% resolution of peri-­implant mucositis in the mechanical
therapy group compared with 29.4% resolution in the erbium-­doped
yttrium aluminium garnet laser group.93 In contrast, the carbon di-
oxide laser was used in conjunction with bone grafting in deep peri-­
implant defects and showed significant bone fill and improvement of
the clinical parameters.94
Surgical treatment for peri-­implantitis consists of regenerative
therapy, resective therapy, or a combination of both. The goal of
resective therapy is to reduce pocketing to allow for more effec-
tive cleaning of the implant and abutment surfaces by the patient
and professionals. Alternatively, regenerative procedures intend to
achieve reosseointegration of the implant surface, often with the
support of graft materials and biologics. Both treatment modalities
include efforts to eliminate biofilm on the implant surface and im-
plant components, utilizing many of the aforementioned debride-
ment instruments and surface treatments.
Direct surgical access to the implant surface allows for some
additional surface decontamination techniques which were not
possible without surgical access. These include more aggressive me-
chanical debridement of the implant surface using titanium or nylon
brushes, removal of the implant surface via implantoplasty (which is
thought to leave behind a less plaque-­retentive surface should it re-
main exposed), and surface treatment with various chemotherapeu-
tic agents. Valderrama and Wilson performed a review of the various
surface treatments that can be combined with surgical access. They
included implantoplasty, air powder abrasion, ultrasonic scaling with
a metal tip, metal curettes, nonmetal curette scalers, citric acid,
chlorhexidine, ethylene diamine tetraacetic acid, hydrogen perox-
ide, saline, tetracycline, erbium-­
doped yttrium aluminium garnet
and carbon dioxide lasers, and photodynamic therapy. The authors
suggest that implantoplasty, air powder abrasion, and cleaning with
metal curettes and metal-­tipped ultrasonics may provide benefits,
while the evidence for the other interventions is weak.95 Ntrouka
et al. performed a systematic review of multiple chemotherapeutic
agents on biofilm removal. Although the authors cautiously con-
clude that citric acid appears to be the most efficacious, multiple
cited studies showed water or saline to be equally as efficacious.96
A comprehensive review of the surgical techniques for treating
peri-­implantitis is beyond the scope of this article. A recent system-
atic review of the topic found an average improvement of 2-­3 mm
(30%-­50%) of the initial probing depth.97 Similarly, other authors
 |
36       DAUBERT and WEINSTEIN

A1 A2
F I G U R E   3   Progression and
appearance of peri-­implantitis over
5 years. (A) 1 year postprosthetic
insertion; (B), 2 year postprosthetic
insertion; (C) 3 year postinsertion after
surgical treatment on left side; (D) 4 year
postinsertion; (E) 5 year postinsertion

B1 B2

C1 C2

D1 D2

E1 E2

have reported about 50% success in treating peri-­implantitis. There 13 | B I O FI LM A N D I M PL A NT FA I LU R E

are some biofilm-­based theories as to why peri-­implantitis treatment
is not more successful, including an inability to remove the biofilm
from moderately rough surfaces, and the rapid reformation of im-
plant biofilm which may take place prior to surgical healing. In addi-
tion, there is evidence that certain implant surfaces, once affected
by peri-­implantitis, have lower treatment success rates than others.98
There has been no conclusive link between implant failure and the
quantity of biofilm present at the time of implant placement. This
may be because of the difficulty in assessing biofilm volume quanti-
tatively. While periodontal indices such as the plaque index do exist,
they are not routinely reported in long-­term retrospective studies
DAUBERT and WEINSTEIN
from which failure data emerges. Instead, most studies utilize pa-
tient periodontal diagnosis and, as previously mentioned, there is
strong evidence of a link between periodontitis severity and implant
failure.3,99,100 It remains to be seen whether certain components of
the periodontitis-­associated flora explain the increased risk of im-
plant failure, or whether host factors account for the linkage.
14  | B I O FI LM A S A N I N FLU E N C E O N
TR E ATM E NT D EC I S I O N S
Given the challenges of treating peri-­
i mplantitis and the in-
creased risk of implant failures in patients who develop biofilm-­
related complications around implants, it seems prudent to
educate patients on the importance of biofilm reduction prior to
implant therapy. Compliance with regular maintenance visits is
an important prerequisite to successful long-­term implant out-
comes. A trackable plaque index such as the Plaque Assessment
Scoring System score101 that can be used in the office may also
help with decisions about when to proceed with elective implant
therapy, and provide patients with a ‘target’ for their oral hygiene
efforts. Reduction of biofilm perioperatively with chlorhexidine
has the potential to reduce the risk of infection and implant fail-
ure. Postoperatively, regular examination for signs of peri-­i mplant
mucositis, and increased maintenance efforts in patients who
show signs of peri-­implant mucositis, can potentially reduce their
risk of peri-­implant mucositis. The maintenance interval must be
tailored to the patient, although the evidence points to main-
tenance at least every 6 months, and the use of subgingival air
powder polishing along with local antimicrobials at each mainte-
nance visit to prevent the transition from peri-­implant mucositis
to peri-­implantitis. Because no differences have been found be-
tween various local antimicrobials, practitioners should consider
features such as safety, cost, and ease of use, in deciding which
of these to use.
15  | FU T U R E D I R EC TI O N S
Previous research has been limited by targeted microbial ap-
proaches. Recent advancements have enabled us to detect the pres-
ence of previously undetected species.
Thus, targeted approaches should only be used when justified
and not as a substitute for open-­ended microbiome analyses. In
addition, clinically relevant in vitro models are required. Previous
studies utilized single strains cultured on titanium substrates to test
various antimicrobials. Newer studies showed that such models were
not clinically relevant because antimicrobials (e.g. chlorhexidine)
having good antimicrobial efficacy against single-­species immature
biofilms were not effective against clinically relevant polymicrobial
biofilms.95 Advancement in the retention media for microcosm bio-
films has enabled the adequate replication of plaque samples from
|
      37
human peri-­implant plaque in bacterial cultures,102 and, as such, in
vitro models should use polymicrobial species.
16  | CO N C LU S I O N S
Biofilm at dental implants is not as similar to teeth as once thought,
both in health and disease. Edentulous patients develop a biofilm
that includes species not found prior to implant placement includ-
ing unique species and species that are associated with periodontal
pockets. The biofilm on implants from partially edentulous patients
also differ from teeth in species and microbial load. The peri-­implant
sulcus is a distinct niche that has less diversity than the periodontal
biofilm. This distinction is because of material properties that are
distinct from natural teeth.
The implant biofilm may be directly influenced by titanium or ti-
tanium corrosive particles, as well as the implant-­abutment connec-
tion, implant surface, and host biofilm. In addition, the host response
to titanium must be considered. It is imperative, going forward, to
treat dental implants in a manner distinct from periodontal therapies
in order to effectively remove the biofilm and simultaneously pre-
serve the titanium surface integrity.
Biofilm reduction during all phases of implant treatment, from
implant placement to maintenance, to treatment of peri-­
implant
disease, is an integral part of implant therapy. Existing therapies for
implant treatment, from placement to maintenance, to treatment of
peri-­implant disease, have been grounded on bacterial removal, du-
plicating treatment of natural teeth. While bacterial removal is the
cornerstone of implant maintenance, there are distinctions between
periodontitis and peri-­implantitis, which justify distinct treatment
approaches. Unlike traditional periodontal therapy in which root
surfaces are debrided using a myriad of chemical and mechanical
means, titanium surface disruption (modification of the titanium
surface by scratching, melting, or otherwise decreasing the biocom-
patibility of implant surfaces) must be carefully considered before
initiating treatment.
AC K N OW L E D G M E N T S
The authors wish to express appreciation to Richard Darveau, PhD,
and Georgios Kotsakis, DDS, MS, Seattle, WA, for editorial review
and guidance.
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How to cite this article: Daubert DM, Weinstein BF. Biofilm
as a risk factor in implant treatment. Periodontol 2000.
2019;81:29–40. https://doi.org/10.1111/prd.12280