J Clin Periodontol 2015; 42: 960–966 doi: 10.1111/jcpe.12457

Bone reconstruction after
surgical treatment ofexperimental peri-implantitis
defects at a sandblasted/acidetched hydroxyapatite-coatedimplant: an experimental study
in the dog

Hee Namgoong1, Myung duck Kim2,
Young Ku1, In-Chul Rhyu1, Yong Moo
Lee1, Yang Jo Seol1, Hee jin Gu2,
€3
Cristiano Susin3, Ulf ME Wikesjo
1and Ki-Tae Koo
1

Department of Periodontology and Dental
Research Institute, School of Dentistry, Seoul
National University, Seoul, Korea; 2Implant
R&D Center, Osstem Implant Inc., Busan,
Korea; 3Laboratory for Applied Periodontal &Craniofacial Regeneration (LAPCR), Georgia
Regents University, College of Dental
Medicine, Augusta, GA, USA

Namgoong H, Kim Md, Ku Y, Rhyu I-C, Lee YM, Seol YJ, Gu Hj, Susin C,
Wikesj€o UME, Koo K-T. Bone reconstruction after surgical treatment ofexperimental peri-implantitis defects at a sandblasted/acid-etched hydroxyapatitecoated implant: an experimental study in the dog. J Clin Periodontol 2015;
42:960–966. doi:10.1111/jcpe.12457.

Abstract
Objectives: The objective of this study was to evaluate bone formation/osseointegration following surgical treatment of experimental peri-implantitis at dental
implants with different surface characteristics exposed to ligature-induced breakdown conditions.
Methods: Ten turned (control), 10 sandblasted/acid-etched (SA), and 10 SA/hydroxyapatite nanocoated (HA) implants were installed into the edentulated posterior mandible in five Beagle dogs and allowed to osseointegrate for 12 weeks.
Ligature-induced breakdown defects were then induced over 23 weeks using stainless steel wire ligatures. The ligatures were removed and soft tissues were allowed
to heal for 3 weeks. Next, exposed implant surfaces were decontaminated followed by guided bone regeneration using a collagen membrane and submerged
wound healing. The animals were euthanized for histometric analysis at 12 weeks
post-surgery.
Results: The radiographic analysis showed vertical bone loss following ligatureinduced breakdown without statistically significant differences among implanttechnologies. The histometric analysis showed significantly enhanced bone formation (height) at SA and SA/HA compared with turned implants (p = 0.028) following reconstructive surgery. Bone formation area was greater at SA/HA
compared with turned implants, however the difference did not reach statisticalsignificance.

Key words: acid-etched surface; animal
study; dental implants; guided boneregeneration; hydroxyapatite; ligature-induced
breakdown
Accepted for publication 4 September 2015

Conflict of interest and source of funding statement
The authors declare no conflict of interest related to this study. The study was supported by a grant from Osstem Implant
Inc., Busan, Korea.

960© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Bone reconstruction after surgical treatment of peri-implantitis defects

961

Conclusions: While ligature-induced defect progression does not appear implantsurface dependent in this animal model, bone formation at the decontaminatedimplant surfaces appears more favourable at SA and SA/HA over turned
implants following reconstructive surgery.

Factors recognized to influence dental implant osseointegration include
implant macro-structure and surface
characteristics. Moderately roughand rough surfaces appear to provide enhanced osseointegration compared with smooth or minimallyrough surfaces (Lang & Jepsen2009). Rough surface implants areproduced modifying the implant surface by means of anodizing, plasma
spraying, acid etching, sandblasting,or combinations thereof. In perspective, sandblasted/acid-etched (SA)surfaces demonstrate significantly
enhanced osseointegration comparedwith turned surfaces (Grassi et al.
2006).
Sandblasting
apparently
achieves preferred roughness formechanical fixation, additional acidetching smoothing sharp surface
peaks to add a high-frequency component to the surface of potential
significance for protein adhesion(Wennerberg & Albrektsson 2009).
Comparing SA with turned andacid-etched implants using a porcine
model,
significantly
increased
removal torque appeared required
for SA implants following a 10-weekhealing interval (Szmukler-Moncler
et al. 2004).
Surface characteristics includinghydrophilicity, chemical bonding,and nanostructures have been developed with the intent to enhance/accelerateosseointegration(Wennerberg & Albrektsson 2010).
A hydrophilic SA surface submergedin NaCl showed increased bone-implant contact compared with ahydrophobic SA surface (Buser et al.
2004).
Calcium-phosphate-coatedimplants demonstrate higher disruption resistance and increased boneimplant contact compared with noncoated implants in a rat femur model(Mendes et al. 2007). Few studies
have investigated the significance ofdental implant surface nanostructures for osseointegration (Meirelles
et al. 2007). Nanostructures attained
through hydroxyapatite (HA) coating have been shown to enhancebone formation (Meirelles et al.
2008a, b, c). HA-coated SA titanium
dental implant surfaces show significantly enhanced mesenchymal stem
cell adherence, increased alkaline
phosphatase activity, osteocalcin
content, and osteopontin mRNA
expression compared with control
SA surfaces in vitro (Wang et al.
2008).
Although favourable outcomes
have been noted in preclinical andclinical settings for micro- andnanostructured implant technologies,
their susceptibility to biofilm-induced
inflammatory processes has caused
concern and their potential to support bone formation/re-osseointegration following regenerative treatment
remains uncertain (Berglundh et al.
2007, Albouy et al. 2011). The objective of this study was to evaluatebone formation and osseointegration
following surgical treatment ofexperimental peri-implantitis at dental implants with different surface
characteristics exposed to peri-implantitis conditions.
Material and Methods
Animals

Five adult male Beagle dogs,
approximate weight 10 kg, acquired
from licensed breeder (OrientBio,
Seoul, Korea), were used. The study
protocol was approved by the Animal Research Committee, Seoul
National University (approval number: SNU-100629-3). All experiments
were performed in accordance with
Institute of Laboratory Animal
Resources, Seoul National University guidelines. ARRIVE guidelines(Kilkenny et al. 2011) were consulted
in reporting this research. The study
outline is shown in Fig. 1. The
experiments were performed March
12, 2010 through September 2, 2011.
The animals were individuallyhoused in W900 9 D800 9 H800
indoor runs, ambient temperature
23  2°C,
relative
humidity© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

50  10%, air-condition 12–18 airchanges/h, light/dark cycle 12/12,
and they were fed a standard pellet
dog-food diet (HappyRang, Seoulfeed Company, Seoul, Korea)
throughout the study and had ad libitum access to water.
Dental implants

Custom ø3.0 9 8.5 mm implants(Osstem, Busan, Korea) manufactured to fit the narrow edentulated
alveolar ridge were used. For theexperimentalgroup,
10
SA(Ra = 2.5 lm) and 10 SA/HAcoated (Ra = 2.5 lm) implants wereused. The HA surface was processed
through thermal acid etching and
HA growth of less than 20 nm(mean 10 nm) thickness. The type ofinterface was a single interface disjointed surface with less than 10 lm
thickness. Single crystalline HA covered almost 50% of the implant surface. For the control group, 10
turned implants (Ra = 0.2 lm) wereused.
Surgical protocol

The animals were anaesthetizedusing xylazine (15 mg/kg IV) andtiletamine/zolazepam (10 mg/kg IV).
All mandibular premolars and firstmolars were extracted and the edentulated alveolar ridges were allowed
to heal for 12 weeks. Next, dental
implant installation was performed.
Turned, SA/HA and SA implants
were randomized to contra-lateraljaw quadrants in subsequent animals
using the 3 9 3 Latin Square
Design. The implants were installed
1 mm subcrestally. Plaque control
using a toothbrush was performed
twice weekly for 12 weeks following
implant installation. Healing abutments were then connected and healing allowed to progress for another2 weeks. Next, stainless steel wire
ligatures were applied at the implantneck to induce peri-implant boneloss (Fig. 2). Plaque control was not962

Namgoong et al.

Fig. 1. Study outline: Placement (Lig+) and removal (Lig ) of ligatures 23 weeks later. Administration of calcein 2 weeks following
guided bone regeneration surgery. Animals were sacrificed and biopsies collected at 12 weeks following surgery.

resorbable collagen membrane (CytoplastÒ, Sybron Implant Solutions,
Orange, CA, USA) was applied overthe implants to provide for guided
bone regeneration and the wounds
closed for primary intention healing.
Graft materials were not used.
Post-surgery procedures

The animals received daily enrofloxacin 10 mg/kg for infection control
and meloxicam 0.04 mg/kg for pain
control for 7 days. They also
received daily a 0.05% chlorhexidine
mouth rinse to support oral hygiene
for 7 days. Calcein fluorescent label(Sigma-Aldrich, St. Louis, MO,
USA; 30 mg/kg IM) was administered at 2 weeks following surgicalintervention (Nkenke et al. 2002).
Intra-oral radiographs were obtained
at 4, 8, and at 12 weeks post-surgery
when the animals were euthanizedand block biopsies harvested for histological analysis.

(A)

Histological processing

(B)

(C)

Fig. 2. Ligature-induced peri-implantitis (A), peri-implantitis defects following flap
surgery and debridement (B), and following application of a collagen membrane for
guided bone regeneration (C).

pursued during this period. Intraoral radiographs were obtained at
weeks 5, 8, 12, 18, and 23 to monitor bone level changes. The wire
ligatures were removed at week 23
and healing abutments replaced withcover screws. Next, the implant sites
were accessed elevating buccal andlingual mucoperiosteal flaps following a 3-week healing interval. Plastic
curettes (Hu-Friedy, Chicago, IL,
USA) were used to remove the granulation tissue. The implant surfaces
were cleaned using a cotton pellet alternately soaked in 0.12% chlorhexidine and saline. In following, a

The tissue blocks were fixed in 10%
neutral buffered formalin for 6 days,
dehydrated, and then embedded
in methacrylate-based resin. The
specimens were sectioned in buccallingual plane, processed to approximately 40–50 lm thickness, andstained using haematoxylin andeosin. One sample per implant closest to the mid-section was analysed
and the unit of analysis was theanimal.
Radiographic analysis

One calibrated experienced masked
examiner (HNG) performed theradiographic analysis using animage-analysis software (Tomoro
Scope Eye 3.5 Image Analyzer,
Techsan Digital Imaging, Seoul,
Korea) and standardized images© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Bone reconstruction after surgical treatment of peri-implantitis defects

Fig. 3. Schematic representation of thehistometric analysis.

IL, USA). Summary statistics ispresented as group means  SD
(N = 5). Differences between groups
were analysed using analysis ofvariance (ANOVA) and post hoccomparisons using the least significant difference (LSD) test. The significance level was set at p < 0.05.
Primary outcome parameter wasbone reconstruction height (N = 5),
while bone reconstruction area andbone-implant contact served as secondary outcome parameters. Intraexaminer reliability was determinedusing the intra-class correlation
coefficient. The intra-class correlation coefficient was 0.976 with a
95% confidence interval of 0.948–
0.989.
Results

obtained using a dental radiographic
unit(ADX4000AT,
Dexcowin,Seoul, Korea). Bone levels from theimplant shoulder to the most coronal extent of bone along the mesial
and distal surface of the implant
were recorded.
Histometric analysis

The same calibrated experienced
masked examiner (HNG) performed
the histometric evaluation twice
using a light microscope and theimage-analysis software (Tomoro
Scope Eye 3.5 Image Analyzer,
Techsan Digital Imaging). The following parameters were evaluatedfor the buccal and lingual surfacesof each implant (Fig. 3):

Radiographic analysis

Peri-implant bone levels gradually
decreased over the sequence ofexperimental peri-implantitis until
ligature removal week 23 (Fig. 4).
Average bone levels at week 26
comprised 2.4  1.0 mm for turned,
2.7  0.6 mm for SA/HA, and2.3  1.0 mm for SA implants without significant differences among
surface technologies (p = 0.773).
Twelve weeks following guided
bone regeneration surgery bonelevels averaged 2.2  0.8 mm forturned, 2.3  0.7 mm for SA/
HA, and 2.0  0.8 mm for SA
implants without significant differences among surface technologies

963(p = 0.700); bone level changes
averaging
0.1  0.4,
0.4  0.7,
and
0.3  0.6 mm,
respectively(Table 1).
Histometric analysis

Mean crestal bone level from theimplant shoulder to the most apicalaspect of the ligature-induced defectamounted to 2.7  1.2 mm forturned, 3.5  1.2 mm for SA/HA,
and 3.2  1.4 mm for SA implants
without significant differences among
implant technologies (p = 0.823).
Bone fill (N = 5) from the fundus of
the defect to the most coronalbone-implant contact of the induced ligature-induced defect comprised 0.1  0.2 mm for turned,
0.5  0.6 mm for SA/HA, and
0.5  0.7 mm for SA implants; SA/
HA and SA implants showing
enhanced bone formation comparedwith turned implants (p = 0.025),
however, without significant differences between SA/HA and SA
implants. Bone reconstruction area
averaged 0.2  0.2 mm2 for turned
compared with 0.5  0.6 mm2 for
SA/HA implants and 0.3  0.4 mm2for SA implants without significant
differences between implant technologies (Fig. 5). Bone-implant contact
withinregenerated
bonecomprised 40.3% for turned compared with 60.9% for SA/HA
implants, and 49.8% for SA
implants without a significant difference differences between implanttechnologies (Table 2).

• Peri-implant defect depth: dis•••

tance from the most apical aspectof the induced peri-implant
defect to the implant shoulder;
Bone reconstruction height: distance from the most apical aspectof the induced peri-implant
defect to the most coronal newbone-implant contact;
Bone reconstruction area: area of
newly formed bone within the
induced peri-implant defect; andBone-implant contact: fraction
bone-implantcontact
withinreconstructed bone.

(A)

(B)

(C)
Statistical analysis

Statistical analysis was performed
using SPSS v.18 (SPSS, Chicago,

Fig. 4. Representative radiographs showing crestal bone levels at weeks 5, 8, 12, 18,
23, and 26 of peri-implantitis defect induction, and at 4, 8, and 12 weeks following
guided bone regeneration for turned (A), SA/HA (B), and SA (C) implants.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

964

Namgoong et al.

Table 1. Radiographic analysis (means  SD in mm; 95% CI, n = 5)

TurnedSA/HA
SA
p-value

Week 5

Week 8

Week 12

Week 18

Week 23

Treatment (Week 26)

Week 4

Week 83Week 120.7  0.5
0.8  0.5
0.7  0.5
0.956

1.6  0.8
1.8  0.4
1.6  0.7
0.796

1.9  0.9
2.1  0.5
1.8  0.7
0.772

2.5  0.9
2.5  0.5
2.4  0.7
0.939

2.4  0.9
2.6  0.5
2.3  0.9
0.773

2.4  1.0
2.7  0.6
2.3  1.0
0.746

2.2  0.8
2.4  0.6
2.2  0.8
0.812

2.1  0.8
2.3  0.6
2.0  0.8
0.697

2.2  0.8
2.3  0.7
2.0  0.8
0.700

g

a

a

b

h

d

j

f

l

b

(A)

i

c

c
d

(B)

k

e
f
e

(C)

Fig. 5. Representative photomicrographs showing overviews (912.5) of turned (A), SA/HA (B), and SA (C) surface implants andmagnification (inserts; 940) of crestal bone levels (haematoxylin & eosin and calcein fluorescent marker).

Discussion

The objective of this study was toevaluateboneformationandosseointegration following surgicaltreatment of experimental peri-implantitis at dental implant surface
technologies – turned, SA/HA, andSA – exposed to ligature-induced

breakdown
conditions
over
23 weeks. The SA and SA/HA surfaces did not prove to be excessively
susceptible to provoked ligature-induced breakdown compared with theturned control as judged from similar depth peri-implant bone defects
for the three surface technologies.
The implants were then subject tosurface decontamination and guided
bone regeneration surgery. Reconstructive surgery resulted in statistically significant increased verticalbone reconstruction at SA/HA andSA surfaces versus that at the control. Only numerical differences infavour of the SA/HA surface relative
to bone reconstruction area and© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Bone reconstruction after surgical treatment of peri-implantitis defects
Table 2. Histometric analysis (means  SD in mm; 95% CI, n = 5)
Peri-implantitis
defect depth

Bone reconstruction
height (mm)Bone reconstruction
area (mm2)Bone-implantcontact (%)

2.7  1.2
3.5  1.2

0.1  0.2*†
0.5  0.6*

0.2  0.2
0.5  0.6

40.3  44
60.9  39

3.2  1.4
0.823

0.5  0.7†
0.025

0.3  0.4
0.420

49.8  39
0.284

TurnedSA/
HA
SA
p-value*p = 0.014.
†
p = 0.021.

osseointegration were observed. In
all, the results suggest that the SA
and SA/HA nanostructured implantsurface technologies may not present
as a significant obstacle to boneformation following exposure toexperimental peri-implantitis conditions.
Resolution of peri-implantitis
defects has been shown influenced
by implant surface characteristics inanimal models. Albouy et al. (2011)
showed improved bone levels following surgical treatment including
mechanical cleaning at turned, titanium plasma-sprayed, and SA
implants, while mucosal swelling/redness and bone loss characterizedhealing at titanium implants with ananodized surface. Parlar et al. (2009)
reported that resolution of peri-implantitis defects at turned, SA, andtitanium plasma-sprayed implants
varied with the surface decontamination
approach,comparatively
favourable bone formation being
observed at SA over that at titanium
plasma-sprayed and turned implants,
differences between implant surface
technologies also observed in thepreset study. However, studies inclinical settings have not been able
to confirm preferred implant surface
characteristics or decontamination
protocols in the management ofadvanced peri-implantitis lesions,only limited effects have beenreported irrespective of approach(Schwarz et al. 2011, 2012, 2013).
Also, the local use of chlorhexidine
has been reported to have minor
influence on surgical resolution of
peri-implantitis(Carcuac
et al.
2015). Clearly, preclinical/clinicalstudies, today limited to surface
technologies or decontamination
protocols, also need to consider
addition of osteoconductive/osteoinductive technologies to approachclinical significance.

The adjunctive use of bone grafting, bone biomaterials, or growth
factors was not considered in thepresent study. Only meticulous
debridement adjunctive to a decontamination
protocolusingachlorhexidine and saline-based protocol (Schou et al. 2003) followed byprovisions for guided bone regeneration was used to focus on possible/
relevant contributions of the decontaminated implant surface to resolution of the adjoining peri-implantitis
defect. SA implants showed a tendency to support greater bone formation than turned implants, while
SA/HA implants showed greaterbone reconstruction than SA andturned implants although observed
differences did not reach statisticalsignificance for the SA/HA and HA
implants. One point of discussion is
the limited reconstruction of alveolarbone averaging 0.5 mm at the SA/
HA and SA implants. Comparable
vertical bone gain (0.7 mm) has beenreported in previous work althoughfollowing minor differences in experimental protocol (Persson et al.
1999). However, immediate comparisons between studies may not bemeaningful due to differences indesign, animal model, implant technologies, time allowed between periimplantitis initiation, reconstruction
and study termination, and analysis.
One should also consider the limited
regenerative potential of alveolarbone shown following guided boneregeneration in a supra-alveolar
defect model (Caplanis et al. 1997,
Wikesj€o et al. 2004). Further, inintra-bony peri-implant defects, theregenerative potential is related tothe depth of the intra-bony defect,
shallow defects such as herein only
allowing limited vertical bone gain.
In perspective, mean peri-implantvertical bone gain in complex
chronic peri-implantitis defects in© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

965

nonhuman primates receiving a
BMP-2 construct amounted to clinically relevant 2.6 mm or 77% of thepartially intra-bony defect compared
to 0.8 mm or 24% for the surgery
control, BMP-2 induced bone providing robust evidence of re-osseointegration,bone-implantcontact
approximating 40% (Hanisch et al.
1997a, b).
In contrast to previous work
evaluating re-osseointegration at various implant surface technologies
following guided bone regeneration
using a canine platform (Wetzel
et al. 1999), re-osseointegration,although limited, was observed in
the present study. The SA/HA surface yielded greater, although notstatistically significant, re-osseointegration compared with SA andturned surfaces. These observations
are in harmony with previous workwhere rough surfaces irrespective ofthedecontamination
protocolshowed enhanced re-osseointegrationcompared to turned controls (Persson et al. 2004). This observation
intriguing in itself in the sense that
biofilm formation is facilitated atrough surfaces (Teughels et al. 2006)
and biofilm decontamination apparently more challenging (Dennison
et al. 1994). However, the absolutedifference between the surface technologies in the present study was too
small to permit a definitive statement. Also, it should be noted thatthe turned implants used in the present
study
were
considerablysmoother than commercially available turned implants. Clearly a systematic study is needed to exploit
the effects of existing and novel
implant surface decontamination
protocols to support much needed
re-osseointegration in clinical settings.
In conclusion, while ligature-induced breakdown does not appear
implant surface dependent in thisanimal model, bone formation andosseointegration at the decontaminated implants appears more favourable at SA and SA/HA surfaced
over turned implants surfaces following surgical treatment.
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this study was to evaluate bone formation and osseointegration at dental implants with different surface
characteristics exposed to experimental peri-implantitis conditions.
Principle findings: The histometricanalysis
showedsignificantly
enhanced bone formation at decontaminatedsandblasted/acid-etched(SA) and SA/hydroxyapatite (HA)nanostructured
implants
overturned implants subject to ligatureinduced
breakdown
following
guided bone regeneration surgery.
Practical implications: SA and SA/
HA nanostructured implant surface
technologies do not appear to provide a significant obstacle to alveolar
reconstruction following exposure
to ligature-induced breakdown.

Address:
Ki-Tae Koo
Department of Periodontology and Dental
Research Institute
School of Dentistry
Seoul National University
28 Yongon-Dong, Chongno-Ku
Seoul 110-749
Korea
E-mail: periokoo@snu.ac.kr© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd