University of Southern California Dissertations and Theses

Regenerative therapy for repair of peri-implantitis: Part I, Radiographic data on case series; Part II, Histologic report and clinical re-entry: case report

(USC Thesis Other)

Regenerative therapy for repair of peri-implantitis: Part I, Radiographic data on case series; Part II, Histologic report and clinical re-entry: case report

PDF

Download

Open document

Flip pages

Download a page range

Download transcript

Copy asset link

Request this asset

Transcript (if available)

Content 1

Regenerative Therapy For
Repair of Peri-implantitis;

Part I- Radiographic Data on Case Series
Part II- Histologic Report and Clinical Re-entry- Case Report

Navid Sharifzadeh

Committee members:
Dr. Homa Zadeh
Dr. Casey Chen
Dr. Michael Paine

Home Department:
Advanced Periodontology
Oral and Craniofacial Biology

University of Southern California

2
Index.
1- Student data- Page 3
2- Committee members’ data- Page 4
3- Part I: Radiographic Data on Case Series
Page 5
4- Abstract- Page 6
5- Introduction- Page 7
6- Aim- Page 13
7- Material and methods- Page 14
8- Results- Page 20
9- Discussion- Page 26
10- Conclusion- Page 32
11- Bibliography- Page 33
12- Part II: Histologic Report and Clinical Re-
entry- case report- Page 39
13- Introduction- Page 40
14- Aim- Page 42
15- Material and methods- Page 43
16- Report- Page 44
17- Discussion- Page 48
18- Conclusion- Page 52
19- Bibliography- Page 53

3

1-Student Data

1-a: Navid
2-a: Sharifzadeh Boshehri
3-a: Doctor of Dental Surgery, Azad
University, School of Dentistry,
Tehran, Iran
4-a: nsharifz@usc.edu
naavidd@gmail.com
5-a: 1111 Wilshire Blvd. Apt #314
Los Angeles, CA 90017

4

2-Committee Members’ Data:

A-Dr. Homa Zadeh
2.A.1 ‐Homa
2.A.2 ‐Zadeh
2.A.3 ‐zadeh@usc.edu
2.A.4 ‐Rank: Associate Professor
2.A.5 ‐Appointment Type: Tenure track
2.A.6-Department: Periodontology

B-Dr. Casey Chen
2.B.1-Casey
2.B.2 ‐Chen
2.B.3 ‐ ccchen@usc.edu
2.B.4 ‐Rank: Professor
2.B.5 ‐Appointment Type: Tenure track
2.B.6 ‐Department: Periodontology

C-Dr. Michael Paine
2.C.1-Michael
2.C.2 ‐Paine
2.C.3-paine@usc.edu
2.C.4 ‐Rank: Professor
2.C.5 ‐Appointment Type: Tenure track
2.C.6 ‐Department: Oral and craniofacial biology

5

3- Part I:

Radiographic
Data On Case
Series

6

4-Abstract

Background. Along with increased number of implants utilized in clinical practice, there has been a rise in the
prevalence of biological complications, including peri-implantitis. Therefore, the availability of efficacious
therapy for peri-implantitis is an important area of investigation. Though many therapies have been proposed
for peri-implantitis, there is paucity of data documenting their efficacy and effectiveness.

Material & Methods. The present case series provides a protocol, which will include mechanical + chemical
implant surface decontamination, as well as regeneration. The protocol entailed removal of the prosthesis,
whenever possible in order to allow the implants to remain submerged under flap during healing.
Mucoperiosteal flap was elevated to gain access to exposed implant surfaces for thorough biofilm removal.
Macroscopically visible mineralized biofilm was removed by titanium brush followed by air powder abrasion,
using sodium bicarbonate powder. Exposed implants were carefully treated with hydrofluoric acid gel for 30
seconds, followed by careful evacuation and copious irrigation with sterile saline and thorough wiping with
gauze soaked in saline. Autogenous bone shavings were harvested within the same surgical area and used to
cover all implant surfaces. Anorganic bovine bone minerals (ABBM; Bio-Oss large particle size) was layered on
top to fill defects up to the level of implant platform and covered with collagen membrane (Bio-Gide). Flaps
were released to approximate the margins in order to achieve primary coverage to submerge the implants
during the healing period. After 3 months, the implants were exposed and the prosthesis was reconnected.

Results. 30 implants were treated in 22 patients, which exhibited mean linear marginal bone loss of
5.85+1.91mm (range 2.28-10.38 mm). Quantitative analysis of the radiographs demonstrated marginal bone
level gain ranging between 0.38 to 7.46 mm (mean of 3.01+1.75 mm) and the mean % defect fill 57.03+22.79%
(range14.85-100%).
Since some of the implants were cement-retained, it was not possible to remove all of those restorations (N=8).
Compared with those cases where the restorations were removed and implants had submerged healing
(N=22), which had 3.55+ 1.61 mm bone gain, non-submerged cases had 1.31+0.88 mm bone gain.
The implant type appeared to influence the degree of bone fill achieved, where 40.40+ 16.26 % and 68.12+
22.37% bone fill was achieved with Anodized surface (N=12) and Tio blast Fluoride modified (N=18) implants,
respectively.
In one case, two implants were reconstructed in this manner and during the second stage surgery, it was
discovered that the implants had been fractured. The implants were removed and histologic evaluation was
performed. Histologic exam demonstrated significant evidence of new bone regeneration in area that had
previously been affected by peri-implantitis.

Conclusions. The protocol for the treatment of peri-implantitis includes:
-Combination of mechanical and chemical implant surface decontamination (titanium brush, air powder
abrasion and acid etching)
-Regenerative therapy: combination of autogenous bone shavings directly on the surface of implants, layered
with anorganic bovine bone minerals and collagen membrane
-Removal of prosthesis to allow primary coverage of regenerated site for minimum of 3 months
The present pilot retrospective data demonstrated efficacy of this protocol. A prospective randomized
controlled clinical trial will be required to investigate the efficacy of the proposed protocol.

Keywords: Peri-implantitis, Peri-implant bone loss, regeneration, implants surface decontamination,
Biofilm

7

5-Introduction

Background. Along with the increased number of implants utilized in clinical practices, there
has been a rise in the incidence of biological complications, which mainly refers to peri-
implant infection or peri-implant disease. Peri ‐implant infections or peri ‐implant diseases
are defined as either (1) peri ‐implant mucositis, where there are clinical signs of
inflammation (bleeding on gentle probing, 0.25 N) of the peri ‐implant mucosa without loss
of supporting bone, or (2) peri ‐implantitis, where there is concomitant loss of supporting
bone. In the case of peri ‐implantitis, probing depths ≥5mm and suppuration are frequently
present(Lang et al., 2011a). There are different measures regarding the specific amount of
bone loss for considering a case as peri-implantitis. Roos-Jansaker(Roos-Jansaker et al., 2011)
considered progressive loss of ≥ 3 threads (1.8 mm) following the first year of healing, in
combination with bleeding and/or pus on probing. In another study, Schwartz(Schwarz et al.,
2009b) defined the presence of an intra-bony defect with a probing depth (PD) of ≥6 mm
and an intra-bony component of ≥3mm as peri-implantitis.
According to recent reviews, peri-implant disease has a prevalence of 20% in patients with
implants.(Atieh et al., 2013; Derks and Tomasi, 2015; Klinge et al., 2012; Mombelli et al., 2012)
Similar to teeth, Oral implants represent hard, non-shedding surfaces in a fluid system and
thus subject to biofilm formation(Mombelli et al., 1988).

The biofilm with its diverse community
of interacting organisms, glycocalyx matrix, and complex structure becomes stable over
time, providing a protective environment from host defenses and antimicrobial
agents(Kolenbrander et al., 2006; Marsh, 2005; Socransky and Haffajee, 2005).
A clear relationship has been established between the formation of microbial biofilms on an
implant surface and an inflammatory response in the host tissues(Lang et al., 2011b).

Therefore, the etiological factors of peri-implant infections are similar to those involved in
periodontal diseases and accordingly the goals of peri-implantitis treatment must be the
resolution of peri-implant soft tissue inflammation and stabilization of the bony attachment
(e.g., the level of osseointegration)(Mettraux et al., 2015).

This will only achieved by access
to the affected implant surface for debridement and decontamination(Froum et al., 2012).

To date, there are no standardized, generally accepted and evidence-based treatment
protocols for the treatment of peri-implant infections(Renvert et al., 2012).

Various protocols,
including mechanical debridement, the use of antiseptics and local or systemic antibiotics,
as well as access and regenerative surgery, have been proposed for the treatment of peri-
implantitis(Esposito et al., 2012).

For the surgical protocols, the primary objective of treatment is to gain access to the
affected implant surface for debridement and decontamination(Lindhe et al., 2008).

Implant surface decontamination. Various implant surface preparation methods have been
used in the surgical treatment of peri-implantitis around titanium implants in animals(Ericsson
et al., 1996; Grunder et al., 1993; Jovanovic et al., 1993; Persson et al., 1999; Persson et al.,
2001a; Persson et al., 1996, 2001b; Schou et al., 2003a; Schou et al., 2003c; Schou et al.,
2003d; Singh et al., 1993). Air-powder abrasive unit, citric acid, delmopinol, chlorhexidine
irrigation, carbon dioxide (CO
2
) laser, rotating brush with pumice, or gauze/cotton pellets
8
soaked in saline and/or chlorhexidine has been used alone or in various combinations.
Histologic investigation did not reveal different treatment outcome after the use of cotton
pellets soaked in saline or rotating brush with pumice(Persson et al., 1999). Moreover, no
difference was found after using air-powder abrasive unit and/or CO
2
laser(Deppe et al.,
2001). Owing to follow the simplest method, utilizing a gauze soaked alternately in
chlorhexidine and saline considered as a preferred implant surface preparation method in
the surgical treatment of peri-implantitis(Schou et al., 2003b).
Decontamination of implant surfaces poses different challenges compared with natural root
surfaces. The concept of the classical periodontal treatment integrates the debridement of
the root surface by means of mechanical instruments, surgical access, if required, and
optimal self- performed plaque control and regular supportive periodontal therapy (SPT).
There is much evidence in periodontal literature to demonstrate that complete calculus
removal is not possible through non-surgical(Buchanan and Robertson, 1987; Waerhaug,
1978) and surgical(Buchanan and Robertson, 1987) methods. Whereas teeth have some
anatomic locations such as furcation and grooves that may be inaccessible to mechanical
instrumentation(Research and Therapy Committee of the American Academy of, 2001),
titanium implants are more geometrically shaped and possibly more accessible. Many of the
instruments used for implant instrumentation have been designed for root surfaces and do
not offer ready application for instrumenting implant threads. Moreover, when micro-
threaded implants are involved in peri-implantitis and covered by bacterial accumulation,
issues regarding meticulous debridement of contaminated implant surfaces have arisen
because the tip widths of conventional instruments, such as curettes and scalers, are much
wider than the narrow inter thread spaces between micro threads of the implants(Park et al.,
2015).

On the other hand, since dental implants are composed of metal, it is possible to use
more abrasive mechanical instruments such as titanium brushes, air powder abrasives and
strong chemical(Froum et al., 2012, 2015).

The surface treatment of implants can involve mechanically removing biofilms and/or
applying antiseptics/ antibiotics. Various mechanical debridement methods, using
mechanical and ultrasonic scalers, curettes, lasers and air-powder abrasion, have been
applied and tested in animals with or without chemical agents, such as chlorhexidine, citric
acid, hydrogen peroxide, and saline(Persson et al., 1999; Persson et al., 2004; Schou et al.,
2003b; Schwarz et al., 2006b; Shibli et al., 2006). However, no single surface decontamination
method has been identified as being superior(Claffey et al., 2008).

Here, recent studies on different implant surface modifications and decontaminations will be
reviewed.

Implantoplasty. A recent study (Ramel et al., 2015) indicated that in addition to soft tissue
excision and osteotomy in an attempt to create favorable bony architecture, implantoplasty
may be indicated usually consisting of removing the implant threads and smoothening
rough implant surfaces with rotary instruments. The purpose of implantoplasty is firstly to polish
the implant surface, thereby removing the entire outmost infected layer of titanium and
creating a new sterile surface structure and secondly to render the affected implant surface
less plaque-retentive by reducing the surface roughness. They concluded that considering
final surface roughness and treatment duration, the use of rotary diamond burs in
decreasing roughness, followed by an Arkansas stone appears to be an optimal treatment
option.
Several clinical studies have proposed that implant detoxification using implantoplasty was
9
effective in arresting disease and regenerating lost bone in practice because a positive
correlation between inflammation and plaque formation around the exposed rough
surfaces of screw-type implants was reported(Romeo et al., 2007; Schwarz et al., 2012;
Subramani et al., 2009; Suh et al., 2003). However, histological analyses of implantoplasty
have commonly described a slight-to-moderate deposition of titanium particles in the sub
epithelial connective tissue adjacent to defects, associated with localized chronic
inflammatory cell infiltrate(Schwarz et al., 2011b).

Laser. Successful clinical treatment outcomes of peri-implantitis were reported after CO2
laser(Deppe et al., 2001; Romanos et al., 2006; Romanos and Nentwig, 2008; Schwarz et al.,
2011b) and diode laser decontamination(Bach et al., 2000). Implant surfaces with calculus
deposits could also be decontaminated with an erbium laser exhibiting ideal absorption
properties in hydroxyapatite and water(Schwarz et al., 2006a; Schwarz et al., 2003; Sculean
et al., 2005).
Recently, Mettraux(Mettraux et al., 2015) showed that non-surgical mechanical debridement
of the implant surface and of the soft tissue wall in conjunction with diode laser application 3
times within 2 weeks resulted in significant clinical improvements after 2 years. These results
were obtained without adjunctive delivery of antiseptics or systemic antibiotics. However; in
this study they did not have any control samples to perform only the mechanical therapy in
order to present the pure effect of laser therapy.
Also, even though the outcome of nonsurgical therapy may be improved by adjunctive
measures (e.g. local antibiotics, air abrasive devices, laser application), moderate to
advanced peri-implantitis lesions commonly require a surgical intervention(Heitz-Mayfield
and Mombelli, 2014; Klinge et al., 2012).

In a recent review by Aoki et al. (Aoki et al., 2015), the capability of various laser types
including diode lasers are in killing bacteria through photo-thermal effects presented.

Photodynamic therapy (PDT). A recent randomized control trial by Sculean(Sculean et al.,
2015) have proposed that in patients with chronic periodontitis, the combination of SRP and
PDT may result in substantially higher short-term clinical improvements evidenced by PD and
BOP reductions compared with SRP alone. However, there is limited evidence from only one
study indicates that PDT may represent a possible alternative to local antibiotics in patients
with incipient peri-implantitis. Therefore, because of limitations in time and costs, the use of
PDT appears to be more suitable in the maintenance phase of therapy. The present study
did not use PDT as a part of the treatment protocol.

Air-powder abrasive systems. They are among the most effective decontamination methods
for implants investigated in previous animal studies(Schou et al., 2004), which can access the
narrow inter- thread spaces; however, side effects, such as alteration of implant surfaces,
mucosal pain, sub mucosal emphysema, and marginal bone loss, have been reported after
repeated clinical use(Bergendal et al., 1990; Kreisler et al., 2005; Schwarz et al., 2009a).

Oral irrigators. Among the home care devices used for daily oral hygiene, dental water jets
(known as oral irrigators)have been reported to be effective in eliminating biofilm from tooth
surfaces(Cobb et al., 1988; Drisko et al., 1987; Gorur et al., 2009; Kreisler et al., 2005; Schwarz
10
et al., 2009a).

In peri-implant disease, the use of a dental water jet with 0.06% chlorhexidine for 3 months
improved certain clinical parameters, such as the plaque index, bleeding index, and
calculus index, in patients with peri-implant mucositis(Felo et al., 1997).

Additionally, a dental
water jet was applied for nonsurgical peri-implantitis treatment with an adjunctive
chlorhexidine gel in a prospective randomized clinical trial, and significant reductions in
probing pocket depths and bleeding on probing were reported(Levin et al., 2015).

In a recent animal study by Park et al.(Park et al., 2015) an effective decontamination
method for implants with micro threads for regenerative peri-implantitis treatment evaluated.
They used dental water jet and dental floss as the decontamination protocol and the validity
of this method evaluated by SEM and histologic examination.

They concluded that decontamination using a dental water jet and dental floss was
effective in the mechanical debridement of micro threaded implant surfaces contaminated
by peri-implantitis. Decontamination using this method was achieved without any changes
in implant surface morphology. In addition, the decontaminated implant surface was able
to achieve re-osseointegration, comparable with the findings of previous studies. The simple
decontamination method introduced in this study could easily be performed at home and in
clinics. It could also be helpful for both maintenance care and regenerative therapy in
patients suffering from peri-implantitis.

Chemicals. Chemical treatments typically employed for debridement of contaminated
surfaces include citric acid, tetracycline, saline, chlorhexidine, hydrogen peroxide,
tetracycline, and doxycycline(de Waal et al., 2015; Finnegan et al., 2010; Gosau et al., 2010;
Valderrama et al., 2014). These chemicals may be applied with various mechanical means
to facilitate biofilm removal.
However, in one of the latest studies regarding this subject, Wheelis(Wheelis et al., 2016)
evaluate the effect of chemicals from another perspective. The study specified that while
the focus of many detoxification studies is the removal of bacterial biofilms, there has been
little emphasis placed on the changes in morphological surface properties that can occur
when an implant is subjected to these treatments. The goal of this study was to do a
qualitative analysis of the effects of decontamination treatments on the morphology of the
titanium oxide layer by using titanium disks exposed to citric acid, 15% hydrogen peroxide,
chlorhexidine gluconate, tetracycline, doxycycline, sodium fluoride, peroxyacetic acid, and
treatment with carbon dioxide laser. The treatments consisted of both immersions of samples
in solution and rubbing with cotton swabs soaked in solution for 1, 2, and 5 min. Cotton
swabs used were analyzed with energy dispersive spectroscopy (EDS). This observation
showed that surface damage of dental alloys might be potentially induced after
detoxification and maintenance treatments with acidic solutions. The results showed that
there is potential damage induced by the use of the treatments investigated in this study.

Experimental peri-implantitis models. Peri-implantitis shares some common features with
periodontitis(Mombelli et al., 1995). The bacterial composition of the biofilm that develops in
pockets around implants is mostly gram-negative and the microbiota is similar to that
associated with periodontitis(Leonhardt et al., 1999). However, more recent studies
demonstrated that, even though bacteria initiate periodontitis and peri-implantitis, there are
significant differences in bacterial composition between the two diseases(Dabdoub et al.,
11
2013). The understanding of peri-implantitis could be facilitated by the development of a
simple, easily reproducible and inexpensive animal model that parallels the clinical
scenario(Pirih et al., 2015). The experimental peri-implantitis model was developed in both
dogs and monkeys and is used to evaluate the pathogenesis and treatment of peri-
implantitis(Ericsson et al., 1996; Lang et al., 1994; Lindhe et al., 1992; Martinez et al., 2014).

The methodology to induce peri-implantitis is dependent on the purpose of the scientific
research(de Molon et al., 2013). Ligature-induced peri-implantitis is one of the most
commonly employed animals models of peri-implantitis. In this model, ligatures placed
around the implant facilitate biofilm accumulation, leading to peri-implant mucosal
inflammation and bone loss(Duarte et al., 2010). Ligature-induced peri-implantitis rodent
models have provided opportunity to examine the events associated with disease initiation
in animal systems with very well-studied genetic and immunologic background (Becker et
al., 2013). In these models, live or dead bacteria or lipopolysaccharide (LPS) are introduced
by inoculation or injections. An innovative model has been developed where titanium
implants inoculated with specific pathogenic bacterial biofilm are cultivated on implants or
their components prior to installation into animals, thus allowing investigation of the role of
specific microorganism in the pathogenesis of peri-implantitis (Freire et al., 2011).
The ligature induced peri-implantitis model has provided valuable information with regard to
the pathophysiology of the disease and some of the therapeutic options(Huang et al., 2015;
Nguyen Vo et al., 2016; Pirih et al., 2015). Specifically, ligature induced peri-implantitis in
canine or non-human primate models has been used extensively to investigate therapeutic
approaches for implant surface decontamination and regenerative therapy. These studies
have provided important insights about treatment of peri-implantitis. On the other hand,
ligature induced peri-implantitis model has some differences with human clinical peri-
implantitis, including: 1) acute nature of the experimentally induced peri-implantitis, 2) lack
of large-scale tenacious mineralized biofilm formation, which is the characteristic of many
clinical cases. Notwithstanding these differences, it is not surprising that differences among
various surface treatment modalities have not been demonstrated in past studies. On the
other hand, in the real, non-experimental clinical environment, most of the diseased implant
surfaces have been contaminated not only with biofilm but also with calculus. (Fig 1.)
Therefore, there is an urge for a solid decontamination protocol prior to any therapeutic
modalities.

Fig 1. Evidence of calcified biofilm on the implant surfaces with severe bone loss.
It is of great interest for the dental community to find ways to treat peri-implantitis and to
12
regenerate the bone that was lost due to the infection. The ultimate goal is re-
osseointegration on the exposed implant surfaces. Several attempts have been made to
determine a treatment protocol that could successfully achieve this. These attempts
included conservative, resective and regenerative treatment in conjunction with various
methods of additional surface decontamination(Renvert et al., 2009).

Regenerative procedures, using bone grafts or bone substitutes, sometimes in combination
with membranes, aimed at reconstructing peri- implant osseous defects have shown
variable results.(Aghazadeh et al., 2012; Khoury and Buchmann, 2001; Roos-Jansaker et al.,
2011; Roos-Jansaker et al., 2014; Roos-Jansaker et al., 2007a; Schwarz et al., 2010; Wiltfang et
al., 2012).However, there is only limited evidence available in the literature to compare the
clinical effectiveness of reconstructive and non-reconstructive procedures(Khoshkam et al.,
2013).

13
6-Aim

The aims of the present study were:
• To evaluate the in vitro effects of different surface decontamination methods on
implant surface topography.
• To examine retrospective data on the marginal bone level changes following peri-
implantitis therapy consisting of implant surface decontamination and guided bone
regeneration.
• To determine the role of various risk factors, such as patient-, implant- or protocol-
associated features, on the outcome of peri-implantitis therapy.
• To assess outcome of peri-implantitis therapy by direct re-entry and histology.

14
7-Material and Methods

1-Implant decontamination. (In-vitro)

In order to evaluate the efficacy of different implant surface treatment modalities, 5 pristine
Astra-tech dental implants (DENTSPLY Co., Germany) with TiO-blasted Fluoride modified
surface were. The micro-threaded portion of the implants was treated according to one the
following methods:
1- Saline-soaked gauze; a gauze soaked with normal saline was used to wipe the micro-
threads of implants for one minute.
2- Air-powder abrasion; The micro-thread part of the implant was subjected for 30
seconds to overlapping passes with the nozzle of an air-abrasive device (Prophy Jet,
Dentsply, USA) using sodium bicarbonate media (27 μm), followed by thorough rinsing
with normal saline for 30 seconds.
3- Acid etch: a micro-applicator was used to apply HF acid (9.6% Hydrofluoric acid gel,
Premier Porcelain Etchant, Plymouth Meeting, PA) to implant surface with overlapping
strokes for 30 seconds, followed by copious irrigation with normal saline.
4- Titanium brush: The micro-threads of implants were debrided with Titanium brush
(Straumann® tiBrush
TM
, Straumann, Switzerland) connected to an oscillating hand-
piece (NSK Dental) run at 600 RPM for one minute in conjunction with copious saline
irrigation.
5- Combination treatment: all four treatment modalities listed above were employed, in
following sequence: 1) titanium brush, 2) air-powder abrasion, 3) HF etch and 4) wiping
with gauze-soaked saline.
All the implants surfaces evaluated under the scanning electron microscope (SEM) at the
Center for Electron Microscopy and Microanalysis (CEMMA) in the Departments of Materials
Science and Biology at the University of Southern California, Los Angeles, California, USA. The
objective of this was to evaluate the quality and quantity of modification in the implant
surfaces in each protocol.
Treated implants were imaged under SEM at 30X, 300X and 3000X magnification. The
samples were examined for topographic surface alteration.

2-Clinical Case series
Patient selection. In this case series, 21 patients (8 males, 13 females; Age range, 39 to 83)
with 30 implants, which were diagnosed with peri-implantitis, were treated in a private
periodontal practice. These patients were followed for a minimum of 6 months and up to 5
years. Two different types of implants were treated in this study. Astra Tech implants (Dentsply
Sirona AB, Molndal, Sweden) with Osseospeed surface (n=18), were grit blasted with Titanium
oxide followed by etching with hydrofluoric acid. Nobel replace select implants (Nobel
Biocare, Yorba Linda, CA, USA with TiUnite® Anodized surface (n=12) were also treated.
None of the peri-implantitis–affected implants demonstrated mobility. The implants were
examined for probing depth (PD), bleeding on probing (BOP), and radiographic evidence of
bone loss. All measurements were made using a UNC-15 periodontal probe that measured
up to 15 mm (Hu-Friedy, USA) around six aspects of the implant. Implants reported on had to
15
demonstrate BOP, PDs ≥ 5 mm, and peri-implant marginal bone loss ≥ 4 mm, as measured
from the implant platform to the coronal-most bone-to-implant contact. Bone loss was
determined by radiographic evidence. However, when the bone loss had been affected
the facial and/or lingual side and it was not possible to determine it radiographically, bone
sounding under the local anesthesia used as the determinant of bone loss. The inclusion and
exclusion criteria to be considered for the retrospective analysis as well as outcome
measures are shown on Table 1. This was performed at the time of surgery and at post
restoration recalls visits. Periapical radiographs were taken prior to and immediately following
restoration and at 3 and 6-month intervals at the patients’ recall visits.

Table1. Inclusion and exclusion criteria along with outcome measures
Inclusion Criteria Exclusion Criteria
Bleeding On Probing Implant mobility/Fracture
Probing depth > 5 Inaccurate Prosthesis driven
Positioning
Radiographic bone loss > 4 mm Incompetency to OHI

Prior to the surgical phase, all patient went through an initial phase of therapy with full mouth
disinfection. According to the CIST (Cumulative Interceptive Supportive Therapy)
protocol(Lang et al., 2000), mechanical debridement, antiseptic and antimicrobial
treatment has been done for all infected implants.
Prior to surgery, attempt was made to remove the prosthesis in order to submerge the
implant under the flap during healing. The basis of this came from the classic article
regarding the concept of guided tissue regeneration around teeth, which showed that there
is greater percent positive regeneration of the attachment apparatus and all component
tissues occurred in submerged intra-bony defects(Bowers et al., 1989a, b, c). However, in
some cases (n=7) where cement-retained restorations were used, it was not possible to
remove the prostheses.

Surgical protocol.

A full mucoperiosteal flap elevated. With regard to coronally positioning of the final flap as
well as obtaining a tension free flap closure, periosteal releasing incisions performed.

All the osseous defects thoroughly debrided with hand and ultrasonic instruments. The
apparent plaque and calculus on the surface of the implants removed with hand
instruments.
The implant surfaces decontaminated performed using the following protocol:
1. Titanium brush (Straumann Ti Brush
TM
, Straumann, Switzerland or R Brush
TM
Neobiotech,
Korea) utilization for a minute with copious amount of irrigation with normal saline.
2. Application of air-abrasive unit (Hu-Friedy, USA) for 30 seconds, then irrigation with
normal saline.
3. Application of Hydrofluoric acid for 30 seconds along with thorough irrigation with
normal saline after.
Autogenous particulate bone graft harvested either from the site of the surgery or from the
16
external oblique ridge on the ascending ramus. The autogenous particulated bone grafts
placed over the exposed threads of the implants in the intra-bony defect compartments.
Anorganic bovine bone mineral (Bio-Oss, Geistlich pharma, Switzerland) placed over the
autogenous graft in the supra-bony compartments. A resorbable collagen membrane (Bio-
guide, Geistlich pharma, Switzerland) utilized to cover the graft materials. (Fig.2)
In some cases due to the thin biotype of the mucosa around the diseased implants, a sub-
epithelial connective tissue graft harvested from either palate or tuberosity placed over the
grafted site.
The flap coronally advanced and sutured with polytetrafluoroethylene (PTFE). All patient had
a loading dose of 2 grams of Amoxicillin 1 hour prior to the procedure and continue as
500mgr every 8 hours for 10 days after. In cases of allergy patients took 600mgr of
Clindamycin 1 hour before and continue by 150mgr every 6 hours for 10 days. Chlorhexidine
0.12 % mouth given to the patient just before the procedure and it was continued as 2 to 3
times per day for 2 weeks. Sutures removed 2 weeks after the surgery. All patients put on a
recall basis every 6-8 weeks up to 6 months. After 6 months, a new radiograph taken and the
site of the surgery probed to evaluate the level of the attachment. Due to the importance of
a professional maintenance
56
, all patient put on exacting 2 to 3 months maintenance and
monitoring appointments.
Magnification in the form of dental loupes or microscope were used during surgical
procedures in order to better visualize biofilm deposits on implants and ensure their complete
removal. The use of dental microscope played a critical role in detection of small pieces of
calculus in between the micro-threads of the dental implants.

Fig 2.
17

Fig2. Representative clinical case of peri-implantitis treated. Pre-operative clinical view following
removal of prosthesis with severe inflammation and suppuration (A, B). Intra-operative view of the
implants following flap reflection showing severe peri-implant bone loss of approximately 5-9mm (C).
Round titanium brush was applied circumferentially around implants (D). Air-powder abrasion with
sodium bicarbonate was used to blast the surface of the implants (E). HF gel was applied for 30
seconds followed by evacuation, irrigation and thorough wiping with gauze soaked in saline (F).
Autogenous bone chips were harvested (G) and placed directly over implant surfaces (H).
Anorganic bovine bone mineral was layered on top of the autogenous bone and covered with
native collagen bilayer membrane (I).

Fig 3.

Fig 3. The flap was approximated to achieve primary coverage in order to submerge the implants
under mucosa (A). By 2 weeks (B), one of the implants became exposed and by 6 months, all three
implants became exposed (C).

Radiographic measurements. The following radiographic outcomes were measured using
Adobe Photoshop software: pre-operative linear marginal bone loss, post-operative linear
marginal bone loss, linear radiographic bone gain, and percentage radiographic bone fill.

Fig 4.: Pre operative (A), immediately post-operative (B)
6-month post operative(C)

Linear bone gains measurements. For the linear bone gain measurements, the part of the
implants with a known measure has been chosen. For instance, the coronal micro threaded
area of the Astra implants was 5mm and the collar height of the Nobel replace select
implants was 1.5 mm. The measurements then calibrated using these known measurements
18
with Adobe Photoshop Software. (Fig. 5-A) The linear initial bone defect measured from the
platform of the implants to most coronal part of the radiographic bone to implant contact.
(Fig. 5-B) The same measurement has done after the surgery as the postoperative linear
bone defect. (Fig. 5-C) The subtraction of these two measurements represented the linear
radiographic bone gain.

Fig 5. Linear bone fill measurement using Adobe Photoshop software. Calibration of the
measurements from pixel to millimeter using the know measurement on an Astra implant(A), Linear
measurement of the initial bone defect(B), Linear measurement of the post operative bone
defect(C).

Percentages of bone fill measurements. For the percentage bone fill measurements three
layers of radiographic image fabricated in Adobe Photoshop software. The first layer was the
initial pre-operative radiograph. The second layer was the surface of initial bone defect,
which detected, outlined and measured using Adobe Photoshop software (Fig 6-A). Then
the post-operative radiograph superimposed on the pre-operative radiograph as the third
layer (Fig 6-B). Then by removing the first layer, there were two layers: First, an outline of the
initial bone defect superimposed on the post-operative radiograph. The residual defect then
detected, outlined and measured within the outline of the initial defect on the post-
operative radiograph using Adobe Photoshop software (Fig 6-C). Then by subtracting the
surface area of the residual bone defect from the initial one, the surface area of the
radiographic bone fill detected and then the percentage calculated.

19

Fig 6. Percentage bone fill measurement using Adobe Photoshop software. Surface area
measurement of the initial defect and outlining the initial defect(A), Super imposing the pre and
post operative radiographs(B), Surface area measurement of the postoperative defect within the
outline of the initial defect(C).

Statistical analysis.
Descriptive statistics were run on the variables of interest. Continuous measures were
summarized using means and standard deviations whereas categorical variables were
summarized using counts and percentages. The distributions of the data were assessed using
the Shapiro-Wilk test, and the variables were not found to deviate significantly from a normal
distribution. Linear mixed models were then run to assess the statistical differences between
the radiographic linear and percentage bone fill difference between Tioblasted Fluoride
modified surface and anodized surface as well as the difference between two different
healing modalities (submerged versus non submerged). The models accounted for the
correlated nature of the data as some patients provided more than one measure. All
analyses were run using SAS version 9.3 (SAS Institute, Cary, NC, USA).

20
8-Results

Scanning Electron Microscope reports:

1-Saline soaked gauze: As expected, there were no alterations found on implant surfaces
(Fig. 7). Therefore, this method was used as control in order to compare with other methods.

Fig 7. Wiping implant surfaces with gauze soaked in normal saline. 100 micron- x30
magnification (A), 10 micron- x300 magnification (B), 1 micron- x3000 magnification (C). It has
been clearly shown that there were no alterations to implant surface.

2-Titanium brush: Application of titanium brush to implant surfaces lead to very significant
changes to surface topography (Fig.8). There were regions that were completely un-altered,
while the micro texture was obliterated in other areas. This treatment created an irregular
surface that may be potentially susceptible to future biofilm accumulation.

Fig 8. Implant surface after application of titanium brush.100 micron- x30 magnification(A), 10 micron-
x300 magnification at peaks(B), 1 micron- x3000 magnification at valley(C), 1 micron- x3000
magnification at peak(D) and 1 micron- x3000 magnification at valley(E). It has been clearly shown
the implant surface alteration by using the titanium brush, which is more profound at the peaks of the
threads.

21

3-Air-powder abrasion with sodium bicarbonate media: Fig 9. shows the effect of air-powder
abrasion device by creating clear pits on the surface of the implant.

Fig 9. Implant surface after application of air abrasive device. 100 micron- x30
magnification(A), 10 micron- x300 magnification at peaks(B), 1 micron- x3000 magnification at
valley(C), 1 micron- x3000 magnification at peak(D) and 1 micron- x3000 magnification at valley(E).
The air abrasive device created pits at the surface of the implant.

4-Hydrofluoric acid gel: HF treatment of titanium surface created a very uniform topography
with numerous pits that were not present with other surface treatments. The original surface
of implants used for this study(Osseospeed) was grit blasted with titanium oxide and etch
with HF. (Fig.10)

Fig 10. Implant surface after application of HF acid. 100 micron- x30 magnification(A), 10 micron- x300
magnification at peaks(B), 1 micron- x3000 magnification at valley(C), 1 micron- x3000 magnification
at peak(D) and 1 micron- x3000 magnification at valley(E). HF acid created an increased surface
area.

5-Combination: The combination of mechanical (TiBrush, air powder abrasion) plus chemical
(HF) lead to the creation of a very uniform surface topography that was similar to that of HF
alone. (Fig.11)

22

Fig11. Implant surface after application of the combination therapy. 100 micron- x30
magnification(A), 10 micron- x300 magnification at peaks(B), 1 micron- x3000 magnification at
valley(C), 1 micron- x3000 magnification at peak(D) and 1 micron- x3000 magnification at valley(E).
This protocol created more uniform pits along with an increased surface area without the presence
of signs of implant surface abrasion

The SEM images were analyzed quantitatively to identify submicron pits, measure their
diameter and number. Results demonstrated that titanium brush surface was devoid of any
pits. Air powder abrasion created 6 pits per µm that were approximately 0.48(µm) in
diameter. HF gel created 5 pits per µm that were approximately 0.23(µm) in diameter.
Combination therapy generated the smallest pits 0.23(µm) with highest density per area
(9/µm). Saline-treated and untreated (not shown) implants had 2 pits per µm that were
approximately 0.65(µm) in diameter. (Table 2.)
Table 2. Surface submicron topography achieved by mechanical and chemical treatment.

Mean Pit Diameter
(µm)
Number
pits/µm
2
Saline 0.65 2
Ti Brush 0 0
Air-Power
abrasion
0.48 6
HF 0.61 5
Combo 0.23
9

Radiographic Results.

A total number of 30 implants from two different surface (TiO-blasted Fluoride modified
(n=18) and Anodized (n=12)) have been evaluated in 21 patients; 8 males, 13 females, Age
range, 39 to 83, mean 61.47+13.70). All the implants diagnosed with peri-implantitis and were
treated and followed for a minimum of 6 months and up to 5 years. The clinical
23
characteristics of study patients comprise demographic data, implant surfaces, healing
mode, pre-operative marginal bone level and post operative linear bone radiographic bone
gain and percentage of bone fill have been demonstrated in table 3. From the 30 implants,
two of them have been removed due to detection of implant fracture at the time of
prosthesis delivery (93.3% Survival rate). A histologic evaluation of the regenerative therapy
has been done for one of the implants, which will be discussed in the second part of this
paper. Implants exhibited mean linear marginal bone loss of 5.85+1.91mm (range 2.28-10.38
mm). Quantitative analysis of the radiographs demonstrated marginal bone level gain
ranging between 0.38 to 7.46 mm (mean of 3.02+1.75 mm) and the mean % defect fill of
57.03+22.79% (range14.85-100%).
Table3. Clinical characteristics of study patients. Demographic data, radiographic pre-op and post-
op marginal bone level (MBL) and percentage defect fill are shown.
Implant
cases:
Patient #-
site number
Patient Bio data
(Age-sex)

Smoker(S)
vs
Non
Smoker(NS)

Implant site
number Implant surface
Healing mode
(Submerged/
Non submerged)
Pre-op MBL(mm)
Post-op MBL
(mm)
Linear
Radiographic
bone gain(mm)
% defect
FILL
1
68- Male

NS
4
TiO-blasted
Fluoride-modified
Non Submerged
4.34 2.36 1.97 68.76
2
62-Female

NS
14
TiO-blasted
Fluoride-modified
Submerged
6.32 3.53 2.78 56.13
3
61-Female

S
31
Anodized Submerged
5.92 4.65 1.27 38.24
4
82-Female

NS
6
TiO-blasted
Fluoride-modified
Non Submerged
5.79 3.10 2.69 58.78
5-1
79-Male

NS
18
TiO-blasted
Fluoride-modified
Submerged
2.65 1.60 1.05 58.81
5-2
79-Male

NS
19
TiO-blasted
Fluoride-modified
Submerged
5.16 2.44 2.72 79.11
6-1
57-Male

NS
30
TiO-blasted
Fluoride-modified
Submerged
5.91 2.15 3.76 55.61
6-2
57-Male

NS
31
TiO-blasted
Fluoride-modified
Submerged
7.12 3.19 3.93 52.57
7-1
71-Female

NS
19
TiO-blasted
Fluoride-modified
Submerged
4.79 0 4.79 100
7-2
71-Female

NS
20
TiO-blasted
Fluoride-modified
Submerged
7.46 0 7.46 100
8
63-Female

NS
6
TiO-blasted Submerged
5.42 2.61 2.81 54.58
24
Fluoride-modified
9
59-Male

NS
30
Anodized Submerged
6.72 3.69 3.03 33.53
10
50-Male

NS
13
TiO-blasted
Fluoride-modified
Submerged
10.38 4.72 5.66 62.57
11-1
65-Female

NS
30
Anodized Non Submerged
5.88 4.87 1.01 52.56
11-2
65-Female

NS
31
Anodized Non Submerged
5.57 3.63 1.93 57.24
12
69-Female

NS 5
TiO-blasted
Fluoride-modified
Submerged
5.83 2.58 3.25 66.08
13
83-Male

NS
30
Anodized Submerged
8.05 5.00 3.05 56.20
14-1
41-Female

NS
7
TiO-blasted
Fluoride-modified
Submerged
4.67 1.81 2.86 42.97
14-2
41-Female

NS
9
TiO-blasted
Fluoride-modified
Submerged
7.93 4.25 3.67 69.36
14-3
41-Female

NS
11
TiO-blasted
Fluoride-modified
Submerged
5.39 2.02 3.37 61.68
15
60-Female

S
14
Anodized Submerged
5.10 2.24 2.86 42.12
16
70-Female

NS
9
Anodized Non Submerged
3.63 2.84 0.80 30.79
17
66-Male

S
14
Anodized Non Submerged
3.30 2.92 0.38 19.93
18
77-Female

NS
30
Anodized Non Submerged
3.68 3.25 0.43 14.85
19-1
53-Male

S
9
TiO-blasted
Fluoride-modified
Submerged
5.47 0 5.47 100
19-2
53-Male

S
10
TiO-blasted
Fluoride-modified
Submerged
5.86 0 5.86 100
20
74-Female

NS
15
TiO-blasted
Fluoride-modified
Submerged
2.28 1.51 0.77 39.21
21-1
39-Male

NS
7
Anodized Submerged
6.38 4.47 1.91 22.07
21-2
39-Male

NS
8
Anodized Submerged
9.63 5.31 4.32 56.68
21-3
39-Male

NS
9
Anodized Submerged
9.12 4.40 4.72 60.64
The Linear radiographic bone gain shown in Table 4 for TiO-blasted Fluoride-modified
implants (3.6+ 1.72 mm) showed marginally significant difference (p=0.06) compared with
implants with anodized surface (2.17+1.48 mm). Moreover, there was a significant difference
25
(p=0.01) in the percentage of radiographic defect fill between two implant systems where
the implants with fluoride modified surfaces demonstrated higher percentage defect fill of
68.12%+ 19.75, while the anodized implants exhibited 40.40%+ 16.27 defect fill.

Table4. Comparison of the linear radiographic bone gain and percentage defect fill between implants
with different surfaces. The results showed a marginally significant difference in favor of the TiO-blasted
implant surface. * P=0.06, **P=0.01

Implant
surface
Radiographic
Linear bone gain
(Mean mm+SD)
Radiographic
Linear bone
gain
(median mm)
Linear bone
gain:
Lower/upper
Quartile
%
Radiographic
bone fill
(Mean
mm+SD)
%
Radiographic
bone fill
(median
mm)
%
defect fill:
Lower/upper
Quartile
Anodized *2.17+1.48 1.92 0.91/3.10 **40.40+16.27 40.18 54.58/69.36
TiO-blasted
fluoride
modified
3.60+1.72 3.31 2.72/4.79 68.12+19.75 62.13 19.93/38.09

The percentage radiographic bone gains for the two modes of healing, i.e. submerged
versus non-submerged was compared (Table 5). A significant difference (p=0.03) was
observed between the two protocols, with higher linear bone gain in submerged (3.55+ 1.59
mm), compared with non submerged (1.26+ 0.94 mm) implants. Also, the submerged
implants yielded 63.65+20.56 % of defect fill, whereas the non-submerged exhibited only
29.71+8.97%; with the difference between the two modes was highly significant (p=0.0005).

Table 5. Comparison of the linear radiographic bone gain and percentage defect fill between
submerged versus non-submerged healing. The results showed a significant difference in favor of the
submerged healing protocol. * P=0.03, **p<0.001

Healing Radiographic
Linear bone
gain (Mean
mm+SD)
Radiographic
Linear bone
gain
(median
mm)
Linear bone
gain:
Lower/upper
Quartile
% Radiographic
bone fill
(Mean mm+SD)
%
Radiographic
bone fill
(median
mm)
%
defect fill:
Lower/upper
Quartile
Submerged
*3.55+1.59
3.25 2.72/4.72
**63.65+20.56 58.81 54.58/69.36
Non
submerged
1.26+0.94 1.01* 0.43/1.93
29.71+8.97 32.52 19.93/38.09
26

9-Discussion

The present retrospective analysis provided radiographic and clinical data on a specific
protocol for the treatment of peri-implantitis. This protocol entails a comprehensive
mechanical and chemical implant surface decontamination in conjunction with
regenerative surgical technique.

Importance of implant surface decontamination. In periodontal literature, studies have
demonstrated that despite absence of complete calculus removal, periodontal parameters
improve. (Badersten et al., 1981; Renvert et al., 1981)
The same concept has not been investigated in dental implant therapy to determine
whether complete removal of mineralized biofilm is a pre-requisite of peri-implant
regeneration. To that end, the present retrospective data demonstrating a very thorough
mechanical and chemical implant surface decontamination may serve as proof-of-concept
evidence in this area. Some of the previous studies have indicated that the clinical
outcomes obtained after combined surgical resective/ regenerative therapy of advanced
peri-implantitis were not influenced by the method of surface debridement and
decontamination(Schwarz et al., 2012; Schwarz et al., 2011a; Wang et al., 2013). However,
these studies have not investigated extend of mineralized biofilm removal and have not
demonstrated regeneration in the presence or absence of mineralized biofilm. It will be
important that future animal and clinical trials address this question of whether complete
mineralized biofilm removal is required for the efficacy of peri-implant bone regeneration.

Another recent study demonstrated the lack of importance of implant surface
decontamination (Schwarz et al., 2015). However, in the same study, in evaluating the cause
of the disease recurrence for two of the case, authors pointed out that it is impossible to
estimate whether these cases has been re-infected or there has been an incomplete
decontamination of the implant surface during the first attempt. This statement is in contrast
with their fact of lack of importance of the implant surface decontamination.
Furthermore, the use of surgical microscope or other forms of magnification is imperative to
ensure thorough mineralized biofilm removal.
Examination of the surface topography following HF or combination therapy demonstrated
the presence of numerous submicron pits. The importance of surface topography in
achieving osseointegration has been amply demonstrated (Renvert et al., 2009).
Notwithstanding, surface texture may also serve as a risk for microbial colonization . (Albouy
et al., 2008)

Long-term follow-up of the patients treated in this study has demonstrated the efficacy of
this protocol. Nonetheless, the fact that residual defect remained in most of the sites
suggests that these patients need strict follow-up maintenance. In particular, the fact that
they have all developed severe peri-implantitis in the first place suggests that they have a
number of risk factors, including: 1) disease susceptibility, 2) lack of adequate oral hygiene
27
and or non-compliance with recommended maintenance care.
As with any therapeutic protocol, it is also important to consider potential risks. In this study air
abrasive system with sodium bicarbonate particles was used as a part of the implant surface
decontamination protocol. In order to avoid the risk of air embolism with the air power
abrasive system, surgeon needs to isolate the area by packing gauze surrounding the
implant and also to direct the stream in such manner as to avoid penetration under the flap.
In the present study, hydrofluoric acid used as a part of the decontamination protocol. The
intraoral application of HF and showed promising results in order to create a smooth unified
implant surface.

Hydrofluoric acid (HF) is an inorganic acid that is used widely in the chemical industries,
electronics manufacturing, glass etching, smelting, cleaning, and other industrial fields. As a
result, a number of chemical burns have been reported as a result of accidental exposure to
HF in these settings. The toxicity of any chemical is directly proportional to its chemical form,
concentration, as well as duration and route of exposure. Certainly, there have been reports
of exposure of relatively small body surfaces to HF with resultant morbidity. However, either
the concentration of HF has been far greater or the surface area of exposure has been
larger or the duration of exposure has always longer than in our clinical cases. The clinical
application for the treatment of peri-implantitis has included placement of approximately
100 microliters 9.6% hydrofluoric gel to implant surfaces for 30 seconds. The material is then
carefully evacuated from the site and then removed by copious irrigation with saline along
with thorough wiping with saline-soaked gauze.
HF is widely used in dentistry. Although most of the applications of HF are extra-oral, it is used
on restorations to repair porcelain. The recommendation is to use rubber dam. However,
rubber dam usage by clinicians is infrequent. Orthodontists use HF intra-orally to bond
orthodontic brackets to porcelain restorations. Rubber dam use by orthodontists has not
been documented in the literature. An informal survey of more than a dozen orthodontists in
private and academic settings from US and other countries revealed orthodontists admit to
either never or rarely using a rubber dam when applying HF intra-orally. Although none of the
other applications of HF have entailed contact with mucosa or bone, there is always
potential for accidental ingestion. To date, there are no reports of adverse reactions to
intraoral applications of HF. Since no incidence on hazardous effects of HF has been
reported in the dental literature, a literature review by Ozcan led to the conclusion that risks
of in vivo and ex vivo use of HF considering the concentrations used in dentistry appears to
be unwarranted(Ozcan et al., 2012).
The rationale for application of HF is two-folds. Firstly, peri-implantitis lesions are often
accompanied by formation of tenacious mineralized biofilm on titanium surfaces and
between the threads. These are very difficult to remove by mechanical means alone. Our
preliminary in vitro studies using titanium brush demonstrated very irregular surface created
by titanium brush and some residual calculus deposits remained. Therefore, additional
treatment may be required to remove residual calculus inaccessible to titanium brush. HF
has been able to generate the uniform surface topography necessary.
Second rationale for application of HF is based on previous data that a number of acids and
chelating agents have been demonstrated to induce bone demineralization and improve
osteogenesis. In a series of animal experiments, it has been shown that demineralization of
autologous bone block graft, as well as the recipient bed improves osteogenesis(de
28
Rezende et al., 2015; Rezende et al., 2014). In these studies, 50% citric acid at pH 1.0 was
used.

There are recent human studies that have used the combination protocols but in a different
approaches. Froum et al (Froum et al., 2012, 2015; Schwarz et al., 2015) used air abrasive
device, saline and chlorhexidine irrigation and minocycline(50mgr/ml).

Parma-Benfenati et al (Parma-Benfenati et al., 2015)utilized plastic ultrasonic tips, titanium
curettes and brushes followed by air abrasive system, photodynamic therapy and
tetracycline application.
Matarasso et al(Matarasso et al., 2014) use different approaches for supra versus intra bony
compartments. An implantoplasty with rotary burs applied for the supra bony area, and for
the intra bony part, air abrasive device with normal saline irrigation administered.
As it is evident, there has not been solid evidence of any advantages or dominances of any
of the above protocols. However, the suggested surface decontamination protocol in this
study is more thorough in comparison to others and provided the in-vitro evidences showing
more uniform surface with capability of biofilm removal.

Regenerative approaches. The same controversy has been presented among the recent
human studies in relation to the type of regenerative materials. In this study, autogenous
bone particulates have been placed in the proximity of the implant exposed threads in the
intra-bony defects and then over contoured with anorganic bovine bone mineral ( Bio-Oss,
Geistlich Pharma, Switzerland)in the supra-bony areas. A resorbable collagen membrane
(Bio-Guide, Geistlich Pharma, Switzerland) covered the graft material. In cases with limited
keratinized mucosa, a sub epithelialized connective tissue graft harvested from either palate
or tuberosity and grafted to the facial flap.

Froum et al(Froum et al., 2012, 2015) used enamel matrix derivative ( Emdogain, Straumann)
or platelet-derived growth factor (PDGF)(Gem 21, Osteohealth) immediately after surface
decontamination.
The defects were then filled by either anorganic bovine bone mineral
(Bio-Oss, Geistlich) or mineralized bone allograft (Puros, Zimmer), which had been hydrated
with platelet-derived growth factor (Gem 21, Osteohealth) at least 5 minutes prior to graft
placement. In cases where limited (< 2 mm) height of keratinized tissue was present, a sub-
epithelial connective tissue graft (SCTG) was harvested from the palate and used as a
barrier to contain the biologic material.

Parma-Benfenati et al(Parma-Benfenati et al., 2015) used a composite graft, hydrated
mineralized freeze-dried human allograft (MinerOss, cancellous and cortical bone,
BioHorizons), combined with autogenous bone chips harvested from the same site using a
bone scraper, was positioned to completely cover the exposed buccal threads and fill the
contiguous mesial and distal bone defects. Hydrated acellular dermal matrix (AlloDerm GBR,
BioHorizons) was properly trimmed to completely cover and stabilize the grafting materials.

In Matarasso et al(Matarasso et al., 2014) study, the intrabony defect was filled with
29
deproteinized bovine bone mineral (DBBM, Geistlich Bio-Oss

0.25–1 mm, Geistlich
Biomaterials, Wolhusen, Switzerland), and a resorbable membrane (Geistlich BioGide,
Geistlich Biomaterials, Wolhusen, Switzerland) was adapted around the implant neck.
In a recent study, Jepsen et al(Jepsen et al., 2016) compare reconstruction of peri-implant
osseous defects with open flap debridement (OFD) plus porous titanium granules (PTGs)
compared with OFD alone. After 12 months, the test group (OFD plus PTG) showed a mean
radiographic defect fill (mesial/distal) of 3.6/3.6 mm compared with 1.1/1.0 in the control
group (OFD). Differences were statistically significant in favor of the test group (P < 0.0001).

Radiographic bone fill. This study showed that the linear radiographic bone gain for TiO-
blasted Fluoride-modified implants (3.6+ 1.72 mm) showed marginally significant difference
(p=0.06) compared with implants with anodized surface (2.17+1.48 mm). Also, there was a
significant difference (p=0.01) in the percentage of radiographic defect fill between two
implant systems where the implants with fluoride modified surfaces demonstrated higher
percentage defect fill of 68.12%+ 19.75, while the anodized implants exhibited 40.40%+ 16.27
defect fill.
The percentage radiographic bone gains for the two modes of healing, i.e. submerged
versus non-submerged was compared in this study. A significant difference (p=0.03) was
observed between the two protocols, with higher linear bone gain in submerged (3.55+ 1.59
mm), compared with non-submerged (1.26+ 0.94 mm) implants. Also, the submerged
implants yielded 63.65+20.56 % of defect fill, whereas the non-submerged exhibited only
29.71+8.97%; with the difference between the two modes was highly significant (p=0.0005).
Mean bone level changes are reflected in a study by Froum (Froum et al., 2015), where the
mean preoperative bone level was 3.80 mm (with a range of 3.01 to 9.56 mm) and the
average bone gain was 1.77 mm (with a range of 0.4 to 9.0 mm) however they did not
evaluate the percentage of bone fill surface and only evaluated the linear bone gain.
Parma Benfenatti (Parma-Benfenati et al., 2015) with an intraoperative measurements
reported a mean bone fill value of 91.3%, ranging from 50% to 100%. The initial defect depths
varied from 3mm to 8mm, with a mean pretreatment defect depth of 5.44 mm. The mean
post-treatment defect depth was 0.44 mm, with a mean bone gain of 4.88 mm.
Matarasso(Matarasso et al., 2014) showed the mean bone level at baseline was 8.0+3.7
mm. After 12 months, this was reduced to 5.2+3.0 mm (P < 0.001). When they considered the
intrabony defect depth, the mean value recorded was 3.5+3.5 and 0.50+1.1 mm at baseline
and at the 12- month follow-up, with a 93.3+13.0% of intrabony defect fill. The difference was
statistically significant (P < 0.001).

Jepsen (Jepsen et al., 2016) compared open flap debridement with the use of Porous
Titanium Granules (PTG) and found significantly higher reductions in vertical defect depth
and gains in marginal bone level favoring the PTG reconstructed group (P < 0.0001). After 12
months, the mean gain of marginal bone level for the test group was 3.61/3.56 mm
(mesial/distal) compared with 1.05/1.04 mm (mesial/distal) in the OFD group. This
corresponded to a mean defect fill for the PTG-treated sites of 79.00%/74.22% (mesial/distal)
compared with 23.11%/21.89% (mesial/distal). No differences in changes in defect width and
horizontal bone level were observed.

Submerged versus non-submerged surgical approach. This study also evaluated the
importance of prosthesis removal and submerging the implants during the healing period.
30
The prosthesis removal can have two potential effects: 1) to facilitate implant surface
decontamination, 2) providing a contained area protected from the oral microorganisms.
This study distinctly presented that the success rate of the surgical approach was significantly
higher in cases where the implants and the grafted areas were completely covered with the
mucosa in comparison to the cases where due to the presence of the prosthesis, the
complete flap closure had not been possible. This result is in agreement with human study of
Bowers et al(Bowers et al., 1989a, b, c) on teeth. In that study data from 9 patients with 25
submerged and 22 non-submerged defects were submitted for statistical analysis. Results
indicate that a new attachment apparatus did not form in any of the 22 non-submerged
teeth; a new attachment apparatus did form in a submerged environment (0.75 mm);
significantly more new attachment apparatus (P less than 0.05), new cementum (P less than
0.01), new connective tissue (P less than 0.05), and new bone (P less than 0.02) formed in
submerged defects; new cementum was cellular in nature and formed equally well on old
cementum and dentin. Greater percent positive regeneration of the attachment apparatus
and all component tissues occurred in submerged defects and no extensive root resorption,
ankylosis, or pulp death was observed on submerged or non-submerged roots.

In a recent study, Benfenati(Parma-Benfenati et al., 2015) demonstrated that different
implant surfaces, defect depths, and defect widths are not discriminating factors for clinical
success if the clinician selects a submerged environment and no exposure of the barrier
membrane occurs. They also mentioned that in contrast to previous studies(Matarasso et al.,
2014; Schwarz et al., 2015; Schwarz et al., 2010) based on their reentry procedure findings,
the use of regenerative procedures with a submerged approach yielded encouraging
positive clinical results even when a supra-crestal peri-implant defect was present. Our study
is in agreement with Benfenati study indicating that regenerative procedures can be done
for supra-crestal peri-implantitis defects.

Implant type. This study also revealed that the Tio blast Fluoride modified implants had a
greater bone gain. There may be two reasons for this observation: 1) inherent reduce ability
to regenerate bone around anodized implant surfaces, as supported by previous study in an
experimental canine model(Albouy et al., 2008). 2) A higher percentage of anodized
implants (41%) had non-submerged healing, compared with 100% of the TiO blasted Fluoride
modified implants.

As with any study, the present investigation has a number of limitations, which include:
1) Limited number of patients and implants have been treated using this protocol
2) The analysis is retrospective in nature and there were no control group(s)
3) The radiographic analysis of defect fill and bone gain was conducted on intraoral
radiographs that are two-dimensional and may not represent the actual degree of
bone fill.
4) The bone graft material used was ABBM, which is radiopaque. Therefore, radiographic
bone fill may not be indicative of gain of supporting bone. Histologic analysis will be
the optimal form to definitively determine the degree of attachment gain.
Nevertheless, a close correlation between radiographic and histologic bone level
values has been observed (Schwarz et al., 2011b).
5) Probing depths of all patients have not been available.

31
A general observation is that most of the patients who developed peri-implantitis had poor
oral hygiene and irregular compliance with maintenance care. One concern with the
outcome of the present approach is that this therapeutic protocol failed to achieve 100%
repair of defects, leaving residual defects. The fact that a rough surface was created may
have been helpful to achieve bone repair. On the other hand, the rough surface in areas
with incomplete bone repair may predispose to increased biofilm accumulation and pose a
risk for relapse. This may be especially problematic in patients with inadequate compliance
with maintenance. Therefore, careful case selection may be required to provide therapy to
those patients who are most likely to adhere to strict maintenance care. Accordingly, in
select cases, where complete defect fill was not achieved, implantoplasty has been
performed in order to eliminate supra-crestal rough surfaces.

A number of unanswered questions remain for the treatment of peri-implantitis. These
questions require further experiments in animal models and more importantly, randomized
control trials to properly investigate the safety and long-term efficacy of this protocol.

32
10-Conclusion

The peri-implantitis therapeutic protocol utilized in the present study entails:

• Combination of mechanical and chemical implant surface decontamination
(titanium brush, air powder abrasion and acid etching)
• Regenerative therapy: combination of autogenous bone shavings directly on the
surface of implants, layered with anorganic bovine bone minerals and collagen
membrane
• Removal of prosthesis to allow primary coverage of regenerated site for minimum of 3
months.

The present pilot retrospective data demonstrated efficacy of this protocol. A prospective
randomized controlled clinical trial will be required to investigate the efficacy of the
proposed protocol.

33
11-Bibliography

Aghazadeh, A., Rutger Persson, G., and Renvert, S. (2012). A single-centre randomized controlled clinical
trial on the adjunct treatment of intra-bony defects with autogenous bone or a xenograft: results after 12
months. J Clin Periodontol 39, 666-673.
Albouy, J.P., Abrahamsson, I., Persson, L.G., and Berglundh, T. (2008). Spontaneous progression of peri-
implantitis at different types of implants. An experimental study in dogs. I: clinical and radiographic
observations. Clin Oral Implants Res 19, 997-1002.
Aoki, A., Mizutani, K., Schwarz, F., Sculean, A., Yukna, R.A., Takasaki, A.A., Romanos, G.E., Taniguchi, Y.,
Sasaki, K.M., Zeredo, J.L., et al. (2015). Periodontal and peri-implant wound healing following laser
therapy. Periodontol 2000 68, 217-269.
Atieh, M.A., Alsabeeha, N.H., Faggion, C.M., Jr., and Duncan, W.J. (2013). The frequency of peri-implant
diseases: a systematic review and meta-analysis. J Periodontol 84, 1586-1598.
Bach, G., Neckel, C., Mall, C., and Krekeler, G. (2000). Conventional versus laser-assisted therapy of
periimplantitis: a five-year comparative study. Implant Dent 9, 247-251.
Badersten, A., Nilveus, R., and Egelberg, J. (1981). Effect of nonsurgical periodontal therapy. I. Moderately
advanced periodontitis. Journal of clinical periodontology 8, 57-72.
Becker, S.T., Foge, M., Beck-Broichsitter, B.E., Gavrilova, O., Bolte, H., Rosenstiel, P., and Wiltfang, J. (2013).
Induction of periimplantitis in dental implants. J Craniofac Surg 24, e15-18.
Bergendal, T., Forsgren, L., Kvint, S., and Lowstedt, E. (1990). The effect of an airbrasive instrument on
soft and hard tissues around osseointegrated implants. A case report. Swed Dent J 14, 219-223.
Bowers, G.M., Chadroff, B., Carnevale, R., Mellonig, J., Corio, R., Emerson, J., Stevens, M., and Romberg, E.
(1989a). Histologic evaluation of new attachment apparatus formation in humans. Part I. J Periodontol
60, 664-674.
Bowers, G.M., Chadroff, B., Carnevale, R., Mellonig, J., Corio, R., Emerson, J., Stevens, M., and Romberg, E.
(1989b). Histologic evaluation of new attachment apparatus formation in humans. Part II. J Periodontol
60, 675-682.
Bowers, G.M., Chadroff, B., Carnevale, R., Mellonig, J., Corio, R., Emerson, J., Stevens, M., and Romberg, E.
(1989c). Histologic evaluation of new attachment apparatus formation in humans. Part III. J Periodontol
60, 683-693.
Buchanan, S.A., and Robertson, P.B. (1987). Calculus removal by scaling/root planing with and without
surgical access. J Periodontol 58, 159-163.
Claffey, N., Clarke, E., Polyzois, I., and Renvert, S. (2008). Surgical treatment of peri-implantitis. J Clin
Periodontol 35, 316-332.
Cobb, C.M., Rodgers, R.L., and Killoy, W.J. (1988). Ultrastructural examination of human periodontal
pockets following the use of an oral irrigation device in vivo. J Periodontol 59, 155-163.
Dabdoub, S.M., Tsigarida, A.A., and Kumar, P.S. (2013). Patient-specific analysis of periodontal and peri-
implant microbiomes. J Dent Res 92, 168S-175S.
de Molon, R.S., de Avila, E.D., and Cirelli, J.A. (2013). Host responses induced by different animal models of
periodontal disease: a literature review. J Investig Clin Dent 4, 211-218.
de Rezende, M.L., Coesta, P.T., de Oliveira, R.C., Salmeron, S., Sant'Ana, A.C., Damante, C.A., Greghi, S.L., and
Consolaro, A. (2015). Bone demineralization with citric acid enhances adhesion and spreading of
preosteoblasts. J Periodontol 86, 146-154.
de Waal, Y.C., Raghoebar, G.M., Meijer, H.J., Winkel, E.G., and van Winkelhoff, A.J. (2015). Implant
decontamination with 2% chlorhexidine during surgical peri-implantitis treatment: a randomized,
double-blind, controlled trial. Clin Oral Implants Res 26, 1015-1023.
34
Deppe, H., Horch, H.H., Henke, J., and Donath, K. (2001). Peri-implant care of ailing implants with the
carbon dioxide laser. Int J Oral Maxillofac Implants 16, 659-667.
Derks, J., and Tomasi, C. (2015). Peri-implant health and disease. A systematic review of current
epidemiology. J Clin Periodontol 42 Suppl 16, S158-171.
Drisko, C.L., White, C.L., Killoy, W.J., and Mayberry, W.E. (1987). Comparison of dark-field microscopy and
a flagella stain for monitoring the effect of a Water Pik on bacterial motility. J Periodontol 58, 381-386.
Duarte, P.M., Tezolin, K.R., Figueiredo, L.C., Feres, M., and Bastos, M.F. (2010). Microbial profile of ligature-
induced periodontitis in rats. Arch Oral Biol 55, 142-147.
Ericsson, I., Persson, L.G., Berglundh, T., Edlund, T., and Lindhe, J. (1996). The effect of antimicrobial
therapy on periimplantitis lesions. An experimental study in the dog. Clin Oral Implants Res 7, 320-328.
Esposito, M., Grusovin, M.G., and Worthington, H.V. (2012). Interventions for replacing missing teeth:
treatment of peri-implantitis. Cochrane Database Syst Rev 1, CD004970.
Felo, A., Shibly, O., Ciancio, S.G., Lauciello, F.R., and Ho, A. (1997). Effects of subgingival chlorhexidine
irrigation on peri-implant maintenance. Am J Dent 10, 107-110.
Finnegan, M., Linley, E., Denyer, S.P., McDonnell, G., Simons, C., and Maillard, J.Y. (2010). Mode of action of
hydrogen peroxide and other oxidizing agents: differences between liquid and gas forms. J Antimicrob
Chemother 65, 2108-2115.
Freire, M.O., Sedghizadeh, P.P., Schaudinn, C., Gorur, A., Downey, J.S., Choi, J.H., Chen, W., Kook, J.K., Chen,
C., Goodman, S.D., et al. (2011). Development of an animal model for Aggregatibacter
actinomycetemcomitans biofilm-mediated oral osteolytic infection: a preliminary study. J Periodontol 82,
778-789.
Froum, S.J., Froum, S.H., and Rosen, P.S. (2012). Successful management of peri-implantitis with a
regenerative approach: a consecutive series of 51 treated implants with 3- to 7.5-year follow-up. Int J
Periodontics Restorative Dent 32, 11-20.
Froum, S.J., Froum, S.H., and Rosen, P.S. (2015). A Regenerative Approach to the Successful Treatment of
Peri-implantitis: A Consecutive Series of 170 Implants in 100 Patients with 2- to 10-Year Follow-up. Int J
Periodontics Restorative Dent 35, 857-863.
Gorur, A., Lyle, D.M., Schaudinn, C., and Costerton, J.W. (2009). Biofilm removal with a dental water jet.
Compend Contin Educ Dent 30 Spec No 1, 1-6.
Gosau, M., Hahnel, S., Schwarz, F., Gerlach, T., Reichert, T.E., and Burgers, R. (2010). Effect of six different
peri-implantitis disinfection methods on in vivo human oral biofilm. Clin Oral Implants Res 21, 866-872.
Grunder, U., Hurzeler, M.B., Schupbach, P., and Strub, J.R. (1993). Treatment of ligature-induced peri-
implantitis using guided tissue regeneration: a clinical and histologic study in the beagle dog. Int J Oral
Maxillofac Implants 8, 282-293.
Heitz-Mayfield, L.J., and Mombelli, A. (2014). The therapy of peri-implantitis: a systematic review. Int J
Oral Maxillofac Implants 29 Suppl, 325-345.
Huang, B., Piao, M., Zhang, L., Wang, X., Xu, L., Zhu, W., and Meng, H. (2015). Ligature-induced peri-implant
infection in crestal and subcrestal implants: a clinical and radiographic study in dogs. PeerJ 3, e1139.
Jepsen, K., Jepsen, S., Laine, M.L., Anssari Moin, D., Pilloni, A., Zeza, B., Sanz, M., Ortiz-Vigon, A., Roos-
Jansaker, A.M., and Renvert, S. (2016). Reconstruction of Peri-implant Osseous Defects: A Multicenter
Randomized Trial. J Dent Res 95, 58-66.
Jovanovic, S.A., Kenney, E.B., Carranza, F.A., Jr., and Donath, K. (1993). The regenerative potential of
plaque-induced peri-implant bone defects treated by a submerged membrane technique: an experimental
study. Int J Oral Maxillofac Implants 8, 13-18.
Khoshkam, V., Chan, H.L., Lin, G.H., MacEachern, M.P., Monje, A., Suarez, F., Giannobile, W.V., and Wang,
H.L. (2013). Reconstructive procedures for treating peri-implantitis: a systematic review. J Dent Res 92,
131S-138S.
Khoury, F., and Buchmann, R. (2001). Surgical therapy of peri-implant disease: a 3-year follow-up study
of cases treated with 3 different techniques of bone regeneration. J Periodontol 72, 1498-1508.
35
Klinge, B., Meyle, J., and Working, G. (2012). Peri-implant tissue destruction. The Third EAO Consensus
Conference 2012. Clin Oral Implants Res 23 Suppl 6, 108-110.
Kolenbrander, P.E., Palmer, R.J., Jr., Rickard, A.H., Jakubovics, N.S., Chalmers, N.I., and Diaz, P.I. (2006).
Bacterial interactions and successions during plaque development. Periodontol 2000 42, 47-79.
Kreisler, M., Kohnen, W., Christoffers, A.B., Gotz, H., Jansen, B., Duschner, H., and d'Hoedt, B. (2005). In
vitro evaluation of the biocompatibility of contaminated implant surfaces treated with an Er : YAG laser
and an air powder system. Clin Oral Implants Res 16, 36-43.
Lang, N.P., Berglundh, T., and Working Group 4 of Seventh European Workshop on, P. (2011a).
Periimplant diseases: where are we now?--Consensus of the Seventh European Workshop on
Periodontology. J Clin Periodontol 38 Suppl 11, 178-181.
Lang, N.P., Bosshardt, D.D., and Lulic, M. (2011b). Do mucositis lesions around implants differ from
gingivitis lesions around teeth? J Clin Periodontol 38 Suppl 11, 182-187.
Lang, N.P., Wetzel, A.C., Stich, H., and Caffesse, R.G. (1994). Histologic probe penetration in healthy and
inflamed peri-implant tissues. Clin Oral Implants Res 5, 191-201.
Lang, N.P., Wilson, T.G., and Corbet, E.F. (2000). Biological complications with dental implants: their
prevention, diagnosis and treatment. Clin Oral Implants Res 11 Suppl 1, 146-155.
Leonhardt, A., Renvert, S., and Dahlen, G. (1999). Microbial findings at failing implants. Clin Oral Implants
Res 10, 339-345.
Levin, L., Frankenthal, S., Joseph, L., Rozitsky, D., Levi, G., and Machtei, E.E. (2015). Water jet with adjunct
chlorhexidine gel for nonsurgical treatment of peri-implantitis. Quintessence Int 46, 133-137.
Lindhe, J., Berglundh, T., Ericsson, I., Liljenberg, B., and Marinello, C. (1992). Experimental breakdown of
peri-implant and periodontal tissues. A study in the beagle dog. Clin Oral Implants Res 3, 9-16.
Lindhe, J., Meyle, J., and Group, D.o.E.W.o.P. (2008). Peri-implant diseases: Consensus Report of the Sixth
European Workshop on Periodontology. J Clin Periodontol 35, 282-285.
Marsh, P.D. (2005). Dental plaque: biological significance of a biofilm and community life-style. J Clin
Periodontol 32 Suppl 6, 7-15.
Martinez, A., Guitian, F., Lopez-Piriz, R., Bartolome, J.F., Cabal, B., Esteban-Tejeda, L., Torrecillas, R., and
Moya, J.S. (2014). Bone loss at implant with titanium abutments coated by soda lime glass containing
silver nanoparticles: a histological study in the dog. PLoS One 9, e86926.
Matarasso, S., Iorio Siciliano, V., Aglietta, M., Andreuccetti, G., and Salvi, G.E. (2014). Clinical and
radiographic outcomes of a combined resective and regenerative approach in the treatment of peri-
implantitis: a prospective case series. Clin Oral Implants Res 25, 761-767.
Mettraux, G.R., Sculean, A., Burgin, W.B., and Salvi, G.E. (2015). Two-year clinical outcomes following non-
surgical mechanical therapy of peri-implantitis with adjunctive diode laser application. Clin Oral Implants
Res.
Mombelli, A., Buser, D., and Lang, N.P. (1988). Colonization of osseointegrated titanium implants in
edentulous patients. Early results. Oral Microbiol Immunol 3, 113-120.
Mombelli, A., Marxer, M., Gaberthuel, T., Grunder, U., and Lang, N.P. (1995). The microbiota of
osseointegrated implants in patients with a history of periodontal disease. J Clin Periodontol 22, 124-130.
Mombelli, A., Muller, N., and Cionca, N. (2012). The epidemiology of peri-implantitis. Clin Oral Implants
Res 23 Suppl 6, 67-76.
Nguyen Vo, T.N., Hao, J., Chou, J., Oshima, M., Aoki, K., Kuroda, S., Kaboosaya, B., and Kasugai, S. (2016).
Ligature induced peri-implantitis: tissue destruction and inflammatory progression in a murine model.
Clin Oral Implants Res.
Ozcan, M., Allahbeickaraghi, A., and Dundar, M. (2012). Possible hazardous effects of hydrofluoric acid
and recommendations for treatment approach: a review. Clin Oral Investig 16, 15-23.
Park, S.Y., Kim, K.H., Shin, S.Y., Koo, K.T., Lee, Y.M., Chung, C.P., and Seol, Y.J. (2015). Decontamination
methods using a dental water jet and dental floss for microthreaded implant fixtures in regenerative
periimplantitis treatment. Implant Dent 24, 307-316.
36
Parma-Benfenati, S., Roncati, M., Galletti, P., and Tinti, C. (2015). Peri-implantitis Treatment with a
Regenerative Approach: Clinical Outcomes on Reentry. Int J Periodontics Restorative Dent 35, 625-636.
Persson, L.G., Araujo, M.G., Berglundh, T., Grondahl, K., and Lindhe, J. (1999). Resolution of peri-
implantitis following treatment. An experimental study in the dog. Clin Oral Implants Res 10, 195-203.
Persson, L.G., Berglundh, T., Lindhe, J., and Sennerby, L. (2001a). Re-osseointegration after treatment of
peri-implantitis at different implant surfaces. An experimental study in the dog. Clin Oral Implants Res 12,
595-603.
Persson, L.G., Ericsson, I., Berglundh, T., and Lindhe, J. (1996). Guided bone regeneration in the treatment
of periimplantitis. Clin Oral Implants Res 7, 366-372.
Persson, L.G., Ericsson, I., Berglundh, T., and Lindhe, J. (2001b). Osseintegration following treatment of
peri-implantitis and replacement of implant components. An experimental study in the dog. J Clin
Periodontol 28, 258-263.
Persson, L.G., Mouhyi, J., Berglundh, T., Sennerby, L., and Lindhe, J. (2004). Carbon dioxide laser and
hydrogen peroxide conditioning in the treatment of periimplantitis: an experimental study in the dog.
Clin Implant Dent Relat Res 6, 230-238.
Pirih, F.Q., Hiyari, S., Barroso, A.D., Jorge, A.C., Perussolo, J., Atti, E., Tetradis, S., and Camargo, P.M. (2015).
Ligature-induced peri-implantitis in mice. J Periodontal Res 50, 519-524.
Ramel, C.F., Lussi, A., Ozcan, M., Jung, R.E., Hammerle, C.H., and Thoma, D.S. (2015). Surface roughness of
dental implants and treatment time using six different implantoplasty procedures. Clin Oral Implants Res.
Renvert, S., Badersten, A., Nilveus, R., and Egelberg, J. (1981). Healing after treatment of periodontal
intraosseous defects. I. Comparative study of clinical methods. Journal of clinical periodontology 8, 387-
399.
Renvert, S., Polyzois, I., and Claffey, N. (2012). Surgical therapy for the control of peri-implantitis. Clin
Oral Implants Res 23 Suppl 6, 84-94.
Renvert, S., Polyzois, I., and Maguire, R. (2009). Re-osseointegration on previously contaminated surfaces:
a systematic review. Clin Oral Implants Res 20 Suppl 4, 216-227.
Research, S., and Therapy Committee of the American Academy of, P. (2001). Treatment of plaque-
induced gingivitis, chronic periodontitis, and other clinical conditions. J Periodontol 72, 1790-1800.
Rezende, M.L., Consolaro, A., Sant'Ana, A.C., Damante, C.A., Greghi, S.L., and Passanezi, E. (2014).
Demineralization of the contacting surfaces in autologous onlay bone grafts improves bone formation
and bone consolidation. J Periodontol 85, e121-129.
Romanos, G., Crespi, R., Barone, A., and Covani, U. (2006). Osteoblast attachment on titanium disks after
laser irradiation. Int J Oral Maxillofac Implants 21, 232-236.
Romanos, G.E., and Nentwig, G.H. (2008). Regenerative therapy of deep peri-implant infrabony defects
after CO2 laser implant surface decontamination. Int J Periodontics Restorative Dent 28, 245-255.
Romeo, E., Lops, D., Chiapasco, M., Ghisolfi, M., and Vogel, G. (2007). Therapy of peri-implantitis with
resective surgery. A 3-year clinical trial on rough screw-shaped oral implants. Part II: radiographic
outcome. Clin Oral Implants Res 18, 179-187.
Roos-Jansaker, A.M., Lindahl, C., Persson, G.R., and Renvert, S. (2011). Long-term stability of surgical bone
regenerative procedures of peri-implantitis lesions in a prospective case-control study over 3 years. J Clin
Periodontol 38, 590-597.
Roos-Jansaker, A.M., Persson, G.R., Lindahl, C., and Renvert, S. (2014). Surgical treatment of peri-
implantitis using a bone substitute with or without a resorbable membrane: a 5-year follow-up. J Clin
Periodontol 41, 1108-1114.
Roos-Jansaker, A.M., Renvert, H., Lindahl, C., and Renvert, S. (2007a). Submerged healing following
surgical treatment of peri-implantitis: a case series. J Clin Periodontol 34, 723-727.
Roos-Jansaker, A.M., Renvert, H., Lindahl, C., and Renvert, S. (2007b). Surgical treatment of peri-
implantitis using a bone substitute with or without a resorbable membrane: a prospective cohort study. J
Clin Periodontol 34, 625-632.
37
Schou, S., Berglundh, T., and Lang, N.P. (2004). Surgical treatment of peri-implantitis. Int J Oral Maxillofac
Implants 19 Suppl, 140-149.
Schou, S., Holmstrup, P., Jorgensen, T., Skovgaard, L.T., Stoltze, K., Hjorting-Hansen, E., and Wenzel, A.
(2003a). Anorganic porous bovine-derived bone mineral (Bio-Oss) and ePTFE membrane in the
treatment of peri-implantitis in cynomolgus monkeys. Clin Oral Implants Res 14, 535-547.
Schou, S., Holmstrup, P., Jorgensen, T., Skovgaard, L.T., Stoltze, K., Hjorting-Hansen, E., and Wenzel, A.
(2003b). Implant surface preparation in the surgical treatment of experimental peri-implantitis with
autogenous bone graft and ePTFE membrane in cynomolgus monkeys. Clin Oral Implants Res 14, 412-
422.
Schou, S., Holmstrup, P., Jorgensen, T., Stoltze, K., Hjorting-Hansen, E., and Wenzel, A. (2003c).
Autogenous bone graft and ePTFE membrane in the treatment of peri-implantitis. I. Clinical and
radiographic observations in cynomolgus monkeys. Clin Oral Implants Res 14, 391-403.
Schou, S., Holmstrup, P., Skovgaard, L.T., Stoltze, K., Hjorting-Hansen, E., and Gundersen, H.J. (2003d).
Autogenous bone graft and ePTFE membrane in the treatment of peri-implantitis. II. Stereologic and
histologic observations in cynomolgus monkeys. Clin Oral Implants Res 14, 404-411.
Schwarz, F., Bieling, K., Bonsmann, M., Latz, T., and Becker, J. (2006a). Nonsurgical treatment of moderate
and advanced periimplantitis lesions: a controlled clinical study. Clin Oral Investig 10, 279-288.
Schwarz, F., Ferrari, D., Popovski, K., Hartig, B., and Becker, J. (2009a). Influence of different air-abrasive
powders on cell viability at biologically contaminated titanium dental implants surfaces. J Biomed Mater
Res B Appl Biomater 88, 83-91.
Schwarz, F., John, G., and Becker, J. (2015). Reentry After Combined Surgical Resective and Regenerative
Therapy of Advanced Peri-implantitis: A Retrospective Analysis of Five Cases. Int J Periodontics
Restorative Dent 35, 647-653.
Schwarz, F., John, G., Mainusch, S., Sahm, N., and Becker, J. (2012). Combined surgical therapy of peri-
implantitis evaluating two methods of surface debridement and decontamination. A two-year clinical
follow up report. J Clin Periodontol 39, 789-797.
Schwarz, F., Nuesry, E., Bieling, K., Herten, M., and Becker, J. (2006b). Influence of an erbium, chromium-
doped yttrium, scandium, gallium, and garnet (Er,Cr:YSGG) laser on the reestablishment of the
biocompatibility of contaminated titanium implant surfaces. J Periodontol 77, 1820-1827.
Schwarz, F., Rothamel, D., and Becker, J. (2003). [Influence of an Er:YAG laser on the surface structure of
titanium implants]. Schweiz Monatsschr Zahnmed 113, 660-671.
Schwarz, F., Sahm, N., Bieling, K., and Becker, J. (2009b). Surgical regenerative treatment of peri-
implantitis lesions using a nanocrystalline hydroxyapatite or a natural bone mineral in combination with
a collagen membrane: a four-year clinical follow-up report. J Clin Periodontol 36, 807-814.
Schwarz, F., Sahm, N., Iglhaut, G., and Becker, J. (2011a). Impact of the method of surface debridement and
decontamination on the clinical outcome following combined surgical therapy of peri-implantitis: a
randomized controlled clinical study. J Clin Periodontol 38, 276-284.
Schwarz, F., Sahm, N., Mihatovic, I., Golubovic, V., and Becker, J. (2011b). Surgical therapy of advanced
ligature-induced peri-implantitis defects: cone-beam computed tomographic and histological analysis. J
Clin Periodontol 38, 939-949.
Schwarz, F., Sahm, N., Schwarz, K., and Becker, J. (2010). Impact of defect configuration on the clinical
outcome following surgical regenerative therapy of peri-implantitis. J Clin Periodontol 37, 449-455.
Sculean, A., Aoki, A., Romanos, G., Schwarz, F., Miron, R.J., and Cosgarea, R. (2015). Is Photodynamic
Therapy an Effective Treatment for Periodontal and Peri-Implant Infections? Dent Clin North Am 59, 831-
858.
Sculean, A., Schwarz, F., and Becker, J. (2005). Anti-infective therapy with an Er:YAG laser: influence on
peri-implant healing. Expert Rev Med Devices 2, 267-276.
38
Shibli, J.A., Martins, M.C., Ribeiro, F.S., Garcia, V.G., Nociti, F.H., Jr., and Marcantonio, E., Jr. (2006). Lethal
photosensitization and guided bone regeneration in treatment of peri-implantitis: an experimental study
in dogs. Clin Oral Implants Res 17, 273-281.
Singh, G., O'Neal, R.B., Brennan, W.A., Strong, S.L., Horner, J.A., and Van Dyke, T.E. (1993). Surgical
treatment of induced peri-implantitis in the micro pig: clinical and histological analysis. J Periodontol 64,
984-989.
Socransky, S.S., and Haffajee, A.D. (2005). Periodontal microbial ecology. Periodontol 2000 38, 135-187.
Subramani, K., Jung, R.E., Molenberg, A., and Hammerle, C.H. (2009). Biofilm on dental implants: a review
of the literature. Int J Oral Maxillofac Implants 24, 616-626.
Suh, J.J., Simon, Z., Jeon, Y.S., Choi, B.G., and Kim, C.K. (2003). The use of implantoplasty and guided bone
regeneration in the treatment of peri-implantitis: two case reports. Implant Dent 12, 277-282.
Valderrama, P., Blansett, J.A., Gonzalez, M.G., Cantu, M.G., and Wilson, T.G. (2014). Detoxification of
Implant Surfaces Affected by Peri-Implant Disease: An Overview of Non-surgical Methods. Open Dent J 8,
77-84.
Waerhaug, J. (1978). Healing of the dento-epithelial junction following subgingival plaque control. II: As
observed on extracted teeth. J Periodontol 49, 119-134.
Wang, D., Kunzel, A., Golubovic, V., Mihatovic, I., John, G., Chen, Z., Becker, J., and Schwarz, F. (2013).
Accuracy of peri-implant bone thickness and validity of assessing bone augmentation material using cone
beam computed tomography. Clin Oral Investig 17, 1601-1609.
Wheelis, S.E., Gindri, I.M., Valderrama, P., Wilson, T.G., Jr., Huang, J., and Rodrigues, D.C. (2016). Effects of
decontamination solutions on the surface of titanium: investigation of surface morphology, composition,
and roughness. Clin Oral Implants Res 27, 329-340.
Wiltfang, J., Zernial, O., Behrens, E., Schlegel, A., Warnke, P.H., and Becker, S.T. (2012). Regenerative
treatment of peri-implantitis bone defects with a combination of autologous bone and a demineralized
xenogenic bone graft: a series of 36 defects. Clin Implant Dent Relat Res 14, 421-427.

39
12-Part II:

Histologic
report and
clinical re-
entry-Case
report

40
13-Introduction

Background. Peri-implantitis leads to inflammation and bone loss in peri-implant tissues,
characterized by bleeding on probing (BoP) and/or suppuration (Pus), clinical and
radiographic loss of supporting bone with or without concomitant deepening of per-implant
pockets(Lang et al., 2011). Peri-implantitis lesions are considerably larger and present with
more aggressive features than lesions in periodontitis around teeth(Carcuac and Berglundh,
2014).

Previous reports on the prevalence of peri-implantitis are associated with several
inadequacies. Tomasi and Derks(Tomasi and Derks, 2012) reported in a review that many
studies provided only implant- based data without considering the number of affected
patients. In addition, analyses were performed on so-called convenience samples of limited
size, and such patient groups may not be representative of the target population(Sanz et al.,
2012). Derks and Tomasi(Derks and Tomasi, 2015) reported in a systematic review a weighted
mean prevalence of peri-implantitis of 22% (95% confidence interval, 14% to 30%) with a
positive relationship between prevalence and time in function of the implants.
In a recent analysis(Derks et al., 2016) the effectiveness of implant therapy in Swedish
population analyzed. In that study, the prevalence of peri-implantitis was assessed and risk
indicators were identified by multilevel regression analysis. Forty-five percent of all patients
presented with peri-implantitis (bleeding on probing/suppuration and bone loss >0.5 mm).
Moderate/ severe peri-implantitis (bleeding on probing/suppuration and bone loss >2 mm)
was diagnosed in 14.5%. Patients with periodontitis and with ≥4 implants, as well as implants
of certain brands and prosthetic therapy delivered by general practitioners, exhibited higher
odds ratios for moderate/severe peri-implantitis. Similarly, higher odds ratios were identified
for implants installed in the mandible and with crown restoration margins positioned ≤1.5 mm
from the crestal bone at baseline. It is suggested that peri-implantitis is a common condition
and that several patient- and implant-related factors influence the risk for moderate/severe
peri-implantitis.
Treatment of peri-implantitis can be inconvenient and uncomfortable for the patient and is
demanding in terms of resources and economy. Thus, as the global number of individuals
that undergo implant therapy increases, so will the prevalence of peri-implantitis, leading to
a growing public health problem in dentistry.(Derks et al., 2016)

The management of peri-implant diseases has become a major issue in implant dentistry.
Although non- surgical mechanical debridement may be effective in controlling mucositis
lesions, this intervention alone seems to have limited efficacy at peri-implantitis sites(Klinge et
al., 2012; Schwarz et al., 2015a).

Even though the outcome of nonsurgical therapy may be
improved by adjunctive measures (e.g., local antibiotics, air abrasive devices, laser
application), moderate to advanced peri-implantitis lesions commonly require a surgical
intervention(Heitz-Mayfield and Mombelli, 2014; Klinge et al., 2012).

Basically, a surgical
protocol should involve the elevation of a mucoperiosteal flap, a complete removal of all
granulation tissue from the defect area, and decontamination of the exposed implant
surface areas(Heitz-Mayfield et al., 2012). This basic procedure may be combined with either
resective (e.g., pocket elimination, bone re- contouring) or augmentative (e.g., bone
substitutes or autografts with or without a supporting barrier membrane) approaches(Claffey
et al., 2008; Heitz-Mayfield and Mombelli, 2014). The clinical outcome of the latter approach
41
seemed to be influenced by several confounding factors, including defect
configuration(Schwarz et al., 2010), type of bone filler(Aghazadeh et al., 2012; Schwarz et al.,
2009),

and characteristics of the implant surface(Roccuzzo et al., 2011).

As it was described in part I of this paper, the main goal of the treatment was to get access
to the implant surface and implement a thorough implant surface decontamination. The
proposed protocol for this purpose was to use titanium brush, air-abrasive device and
Hydrofluoric acid along with copious amount of irrigation. The regenerative phase started
with autogenous bone grafting along the exposed threads of the implants in the intra-bony
defects, then adding the xenograft material in the supra-bony areas and covered the whole
graft with a collagen membrane.

42
14-Aim

The part I of this study presented the radiographic bone gain of the peri-implantitis defects
treated with this protocol. The aim of the second part is to depict two essential criteria of the
regenerative therapy. First, for the first time in human, this study provided the histologic report
of an implant retrieved after regenerative attempt for treating peri-implantitis and
documented the characteristics of re-osseointegration on a previously contaminated dental
implant. Second, the clinical result of the regenerative therapy evaluated through re-entry
direct visualization.

43
15-Material and Methods

Two patients (males, 50 and 74 years old) had the history of restoring the partial edentulous
area in the posterior mandible. After restoring the edentulous areas, both patients faced
postoperative complications, which diagnosed as peri-implantitis 3 years later. In both
cases, implant surface decontamination as well as regenerative surgery has done based on
the protocols described in the part I of this paper. Healings were uneventful for both cases.
In case one, at tenth month, the implant fixture diagnosed with fracture with a hopeless
prognosis. The implant removed and a histology done to evaluate the type of regeneration.
In case two, after 18 months, the implant had a screw fractured and patient returned back
for a check up. At the time of re-evaluation, due to the bone loss on tooth #20, it has been
decided to extract #20 and replace it with a dental implant. During the surgical phase, a re-
entry has been done to clinically evaluate the magnitude of the bone gain on the
circumferential component of the defect around implant #19.

44

16- Reports

Case 1- Histologic report. In August 2008, two Astra Tech Osseospeed dental implants
(mandibular first molar: 4.0 x13mm and second molar: 4.0 x 11mm) had been placed to
restore the partial edentulous sites of mandibular first and second molars for a 50-year-old
male (Fig1-A). He had history of type 2 diabetes mellitus with moderate glycemic control
(A1c=7.5) and high body mass index. Dental history was significant for generalized severe
chronic periodontitis and heavy bruxism In March 2011, patient presented with mucosal
inflammation, bleeding on probing and deep probing depths of 6-9mm around those
implants. Periapical radiograph showed peri- implant bone loss around both implants (Fig1-
B). After the initial therapy, the screw-retained prosthesis was removed, a mucoperisteal flap
was reflected, implants were decontaminated with titanium brush, air-powder abrasion, HF,
which was evacuated after 30 seconds, followed by copious irrigation with saline. The bone
loss was reconstructed with a combination of anorganic bovine bone minerals and
recombinant human bone morphogenetic (rhBMP)2. The implants were submerged under
the flap for the healing period (Fig1-C). On a date after surgery, while examining intra-
operative surgical photographs, it was discovered that both implants had cracks at their
platforms. This is likely attributed to patient’s heavy bruxism. The patient was informed about
these findings and was recommended to have the implants removed. After six months, the
implants were removed with trephine (Fig2.) and the sites were grafted in preparation for
new implants. The retrieved implants were processed for histologic examination using ground
sectioning which demonstrated direct bone-to implant contact in regions of implants that
had previously been demonstrated in both radiograph and during surgery to have lost their
bone attachment. Quantitative examination of the bone-to-implant provided evidence for
re-osseointegration to implant surfaces that had been decontaminated and regenerated
according to the protocol of the present study. The gain of new bone height were 4.02mm,
3.49mm, 3.79mm and 3.71mm on mesial and distal aspects of the anterior and posterior
implants, respectively. To calculate the histological level of bone-to-implant contact, the
image of the trephined implant evaluated in Photoshop software and the bone level
measured. For the 10 mm implant, the level of the attachment was at 5.41 mm.

Fig1. A. Implant placement and restoration (2008), B: Post operative visit (2011), C: immediately post surgical treatment
45

Fig 2. Implants retrieved with a trephine bur

Fig 3. Histology of new bone formation and re-osseointegration on previously contaminated dental implant.

Case 2- Re-entry. Three Astra Tech Osseospeed implants were placed in the mandibular left
posterior region for a 74-year-old male, who was otherwise healthy (Fig. 4-A). During a follow-
up visit approximately three years later, radiographic examination revealed severe peri-
implant circumferential bone loss around the mandibular first molar implant (Fig. 4-B). The
therapeutic protocol for the implant entailed prosthesis removal (Fig. 4-C) and reflection of a
mucoperiosteal flap (Fig. 5-A,B). Implant surface decontamination involved application of
titanium brush, air-powder abrasion, HF application (Fig. 5-C) for 30 second followed by
thorough irrigation and wiping with saline-soaked gauze (Fig. 5-D) . A sub-epithelial
connective tissue graft was harvested from palate and sutured to the buccal flap, which
was approximated in order to submerge the two posterior implants under flap (Fig. 5-F). The
intra-osseous defect was grafted with autogenous bone chips (Fig. 5-E) that were placed
directly on implant surface along with anorganic bovine bone minerals layered on top (Fig.
5-G). The particular graft material was covered with native bilayer collagen membrane (Fig.
5-H). Surgical site healed well and the implants remained submerged under mucosa during
the three months healing period. A small incision was made over each implant to be able to
re-connect the abutments and the prostheses. After one year of function, the abutment
screw fractured (Fig. 6-A). When the patient returned mucosa had covered the implant. A
mucoperiosteal flap was made to retrieve the fractured screw fragment. This allowed direct
46
visualization of the implant, demonstrating successful fill of the circumferential component of
the peri-implant bone (Fig. 6-B).

Fig 4. A: Prosthesis delivery (October 2011). B: Peri-implantitis diagnosis (July 2014). C: Prosthesis removal and initial therapy.
D: 3 months post operative-Prosthesis delivery

Fig 5. Step by step parts of the surgical procedure.

47

Fig 6. A: Pre-operative. B: 18 months post operative with clear evidence of newly formed bone in the previously intra-bony
defect.

48

17- Discussion

The present report, demonstrates examination of the outcome of implants with severe peri-
implantitis following surface decontamination, guided bone regeneration and submerged
healing. In one case, the treated implant was visualized by re-entry and direct examination.
In another case, the treated implants were retrieved and examined by histologic
assessment. Although re-osseointegration on previously contaminated implant surfaces has
been demonstrated in animal studies(Alhag et al., 2008; Parlar et al., 2009; Persson et al.,
2001; Schou et al., 2003b; Schwarz et al., 2006; Schwarz et al., 2011a; Shibli et al., 2006), this is
the first human histologic report of its kind. Reentry evidence cannot determine if re-
osseointegration has taken place between the newly formed bone and the treated implant
surface whereas histology provides proof-of-principle evidence of re-osseointegration.
Histologic examination is the most definitive method to determine the nature of
regeneration.
Naturally occurring human peri-implantitis lesions often feature a combined defect
configuration including a supracrestal and an intrabony aspect (Schwarz et al. 2007). The
initial defect morphology is likely an important factor in the degree of defect fill achieved,
where the intrabony aspect are more amenable to bone fill. This may partly explain the
difficulties in obtaining complete defect fill in most of the cases in this case series. On the
other hand, animal defects are generally created at accelerated rate, causing more
vertical defects. Complete defect fill has been more commonly achieve in several animal
studies(Ericsson et al., 1996; Hanisch et al., 1997; Persson et al., 1999; Persson et al., 1996;
Wetzel et al., 1999).

Possible factors influencing “re-osseointegration” may include the surface texture of the
implant, bone defect morphology, membrane/implant exposure, and/or alteration of the
reactive superficial titanium oxide during the decontamination procedure or during
surgery(Nociti et al., 2001).
It is still unclear if submerged healing and/or the application of a membrane may result in
better clinical outcomes in regenerative procedures for treating peri-implantitis. Currently,
there is no available clinical trial comparing the outcomes of submerged versus non-
submerged healing. However, one pre-clinical study has reported more favorable outcome
in submerged healing(Schwarz et al., 2006). The meticulous surface decontamination
method employed in treating these two cases might have accounted for the favorable
outcome. In this study, decontamination of the implant surface was initiated with rotating
titanium brush, which provides easier access to narrow spaces and readily adapted to the
architecture of the implant(John et al., 2014). It is noteworthy that the treatment with the
titanium brush does not significantly change the roughness parameters in moderate rough
surfaces thus not interfering with re-osseointegration(Park et al., 2015)
Some studies have suggested that osseointegration can only be achieved on pristine and
not previously contaminated implant surfaces(Ericsson et al., 1996; Grunder et al., 1993;
Persson et al., 1996, 2001; Wetzel et al., 1999). They demonstrated that (i) significant re-
49
osseointegration failed to occur to implant surfaces exposed to bacterial contamination
following traditional treatment of peri-implantitis lesions (ii) such integration consistently
occurred at sites where a pristine implant component was placed in the bone defect
following surgical debridement. On the other hand, the ability to achieve re-osseointegration
on previously contaminated surfaces can achieved in other studies(Alhag et al., 2008;
Renvert et al., 2009).
Ligature-induced peri-implantitis in dogs has been created and implant surfaces were
decontaminated after open flap using different techniques: (1) swabbing with citric acid for
30 s followed by rinsing with physiological saline, (2) cleansing with a toothbrush and
physiological saline for 1 min, and (3) swabbing with 10% hydrogen peroxide for 1 min
followed by rinsing with physiological saline. In all cases, incomplete defect fill has also been
demonstrated. This may either be due to incomplete surface decontamination or due to
lack of grafting(Alhag et al., 2008).
Regenerative and resective approach to the treatment of peri-implantitis have been
experimentally compared (Schwarz et al., 2011b). Following creation of advanced ligature-
induced peri-implantitis in dogs, the intrabony component was filled with anorganic bovine
bone mineral (ABBM) and the supracrestal component was treated by either the application
of an equine bone block or implantoplasty. The anorganic bovine bone mineral and equine
bone were soak-loaded with recombinant human bone morphogenetic protein (rhBMP-2) or
sterile saline. All sites were covered by a native collagen membrane and left to heal in a
submerged position for 12 weeks. Results demonstrated high rate of implant exposure and
lack of complete defect resolution.
In a paper by Kolonidis et al.(Kolonidis et al., 2003), it was demonstrated that
osseointegration could occur on turned surfaces that were plaque contaminated and
cleaned by three different methods.
In a systematic review, Renvert(Renvert et al., 2009) searched the literature for the existing
evidence of re- osseointegration after treatment of peri-implantitis at contaminated implant
surfaces. He concluded that based on the basis of animal studies, re-osseointegration;
• Is possible to obtain on a previously contaminated implant surface,
• May occur in experimentally induced peri-implantitis defects following therapy,
• Varied considerably within and between studies and is unpredictable,
• May be influenced by the implant surface characteristics,
• Has not be achieved for the entire previously contaminated implant surface by any of
techniques tested.
The importance of surface treatment has been demonstrated in a study where regenerative
therapy was attempted on implants comparing lethal photosensitization to mechanical
debridement of implant surfaces(Shibli et al., 2006). Re-osseointegration of approximately
one third of defects has been observed following lethal photosensitization of implant
surfaces compared to 0-14% of the sites treated by mechanical debridement.
The importance of defect morphology has been demonstrated by a number of studies. Re-
50
osseointegration was achieved on all dental implant surfaces principally at the base of the
angular bony defect(Shibli et al., 2006), in agreement other previous studies(Jovanovic et al.,
1993; Persson et al., 1996; Singh et al., 1993).
The effect of the implant surface on the outcome of re-osseointegration has been
demonstrated in a number of studies(Albouy et al., 2008).
The ability to achieve re-osseointegration on previously contaminated surfaces has also
been demonstrated in non-human primate experimental model. In this study, the different
surface decontamination methods did not lead to different outcomes(Schou et al., 2003a).
On the other hand, combination of autogenous bone and ePTFE membrane leads to the
best regenerative outcome(Schou et al., 2003b).
The type of membrane, namely collagen membrane vs nonabsorbable PTFE membrane
have not been found to have a significant effect on the outcome of peri-implant
regeneration outcome Nociti(Nociti et al., 2001).

Traditionally, clinical parameters including probing depth reduction, clinical attachment
level gain, changes in mucosal levels, and defect fill as ascertained on peri-apical
radiographs have been employed to evaluate the response of peri-implant structures to
reconstructive procedures for the management of peri-implantitis. Given that the majority of
peri-implantitis defects occur circumferentially around the implants(Schwarz et al., 2010) one
limitation of relying on radiographs to assess the amount of defect fill is the inability to
visualize the amount of defect fill in buccal and lingual surfaces. Additionally, in the
evaluation of the regenerative approaches to treat peri-implantitis it is difficult to discern
between newly formed osseous tissue and the radiopaque grafting material. Surgical reentry
allows direct visualization and evaluation of the quality and quantity of circumferentially
newly formed bone compared to conventional radiographs that only demonstrate changes
in interproximal bone levels.

Froum and Rosen(Froum and Rosen, 2014)

showed twelve implants with peri-implantitis
underwent reentry flap surgery in five patients 6 to 96 months post-regenerative surgery. The
reason was to evaluate the necessity for additional treatment or new treatment of adjacent
or other implants in close proximity to the original implant. Clinical measurements of the
original depth of bone lesions ranged from 3 to 12 mm. Bone fill occurred around all implants
and ranged from 2 to 9 mm, representing 40% to 100% of the original defect depth. These
direct bony measurements support radiographic and sounding data in a previous report that
recorded a mean of over 3 mm of bone fill in the defects treated with the specific
regenerative approach used in their study. The results of their clinical series were
encouraging; however, as it was mentioned by them, histologic research was necessary to
determine if re-osseointegration occurred, with direct visual evidence suggesting new bone
formation, and more multicenter studies will be needed to verify the results.

Schwarz(Schwarz et al., 2015b)

retrospectively analyzed five reentry cases reports on the
clinical defect healing after combined surgical resective/regenerative therapy of advanced
peri-implantitis. The second surgery was necessary because of a clinical need for additional
treatment procedures at the respective implant sites after healing periods of 8 months to 6.5
51
years. All patients underwent the same standardized procedure including access flap
surgery, implantoplasty at bucally and supracrestally (> 1 mm) exposed implant parts,
surface decontamination, and augmentation of the intra-bony components using a natural
bone mineral and a native collagen membrane. Clinical defect resolution of the was
evaluated. Mean defect resolution values ± standard deviation were 59.4% ± 47.59%.The
presented surgical procedure was associated with a clinically important DR in advanced
peri-implantitis defects.

In a case series, Benfenati(Parma-Benfenati et al., 2015) presented clinical outcomes on
reentry using regenerative submerged and non submerged approaches in peri-implant
defects; pre- and post treatment assessments of nine implants in six patients. They concluded
that the regenerative procedure was effective in the treatment of moderate to advanced
peri-implantitis lesions without compromising the previous fixed implant-supported prostheses.
Their preliminary results were reasonably encouraging in that all cases showed bone gains.

Additional studies will be required in order to address a number of remaining open questions.
These include: 1) whether complete implant surface decontamination such as that
presented in the present case report is required or if some biofilm remains, re-
osseointegration can still be achieved, 2) what is the long-term effects of leaving defect sites
that have been incompletely regenerated and 3) what are optimal methods of surface
decontamination and peri-implant regeneration. Additional experimental animal studies, as
well as randomized control clinical trials will be required to address these and other
important questions regarding the management of peri-implantitis.

52
18- Conclusion

The present report using re-entry and histologic examination demonstrates evidence for re-
osseointegration achieved around implants previously affected by severe peri-implantitis.
The evidence presented provides support for the safety and efficacy of a therapeutic
protocol involving surface decontamination (titanium brush + air-powder abrasion + HF
etching), regeneration and submerged healing. Randomized control clinical trial is merited
to definitively examine the safety of efficacy of peri-implantitis therapy.

53
19- Bibliography

Aghazadeh, A., Rutger Persson, G., and Renvert, S. (2012). A single-centre randomized controlled clinical
trial on the adjunct treatment of intra-bony defects with autogenous bone or a xenograft: results after 12
months. J Clin Periodontol 39, 666-673.
Albouy, J.P., Abrahamsson, I., Persson, L.G., and Berglundh, T. (2008). Spontaneous progression of peri-
implantitis at different types of implants. An experimental study in dogs. I: clinical and radiographic
observations. Clin Oral Implants Res 19, 997-1002.
Alhag, M., Renvert, S., Polyzois, I., and Claffey, N. (2008). Re-osseointegration on rough implant surfaces
previously coated with bacterial biofilm: an experimental study in the dog. Clin Oral Implants Res 19,
182-187.
Carcuac, O., and Berglundh, T. (2014). Composition of human peri-implantitis and periodontitis lesions. J
Dent Res 93, 1083-1088.
Claffey, N., Clarke, E., Polyzois, I., and Renvert, S. (2008). Surgical treatment of peri-implantitis. J Clin
Periodontol 35, 316-332.
Derks, J., Schaller, D., Hakansson, J., Wennstrom, J.L., Tomasi, C., and Berglundh, T. (2016). Effectiveness of
Implant Therapy Analyzed in a Swedish Population: Prevalence of Peri-implantitis. J Dent Res 95, 43-49.
Derks, J., and Tomasi, C. (2015). Peri-implant health and disease. A systematic review of current
epidemiology. J Clin Periodontol 42 Suppl 16, S158-171.
Ericsson, I., Persson, L.G., Berglundh, T., Edlund, T., and Lindhe, J. (1996). The effect of antimicrobial
therapy on periimplantitis lesions. An experimental study in the dog. Clin Oral Implants Res 7, 320-328.
Froum, S.J., and Rosen, P.S. (2014). Reentry evaluation following treatment of peri-implantitis with a
regenerative approach. Int J Periodontics Restorative Dent 34, 47-59.
Grunder, U., Hurzeler, M.B., Schupbach, P., and Strub, J.R. (1993). Treatment of ligature-induced peri-
implantitis using guided tissue regeneration: a clinical and histologic study in the beagle dog. Int J Oral
Maxillofac Implants 8, 282-293.
Hanisch, O., Tatakis, D.N., Rohrer, M.D., Wohrle, P.S., Wozney, J.M., and Wikesjo, U.M. (1997). Bone
formation and osseointegration stimulated by rhBMP-2 following subantral augmentation procedures in
nonhuman primates. Int J Oral Maxillofac Implants 12, 785-792.
Heitz-Mayfield, L.J., and Mombelli, A. (2014). The therapy of peri-implantitis: a systematic review. Int J
Oral Maxillofac Implants 29 Suppl, 325-345.
Heitz-Mayfield, L.J., Salvi, G.E., Mombelli, A., Faddy, M., Lang, N.P., and Implant Complication Research, G.
(2012). Anti-infective surgical therapy of peri-implantitis. A 12-month prospective clinical study. Clin
Oral Implants Res 23, 205-210.
John, G., Becker, J., and Schwarz, F. (2014). Rotating titanium brush for plaque removal from rough
titanium surfaces--an in vitro study. Clin Oral Implants Res 25, 838-842.
Jovanovic, S.A., Kenney, E.B., Carranza, F.A., Jr., and Donath, K. (1993). The regenerative potential of
plaque-induced peri-implant bone defects treated by a submerged membrane technique: an experimental
study. Int J Oral Maxillofac Implants 8, 13-18.
Klinge, B., Meyle, J., and Working, G. (2012). Peri-implant tissue destruction. The Third EAO Consensus
Conference 2012. Clin Oral Implants Res 23 Suppl 6, 108-110.
Kolonidis, S.G., Renvert, S., Hammerle, C.H., Lang, N.P., Harris, D., and Claffey, N. (2003). Osseointegration
on implant surfaces previously contaminated with plaque. An experimental study in the dog. Clin Oral
Implants Res 14, 373-380.
Lang, N.P., Berglundh, T., and Working Group 4 of Seventh European Workshop on, P. (2011). Periimplant
diseases: where are we now?--Consensus of the Seventh European Workshop on Periodontology. J Clin
Periodontol 38 Suppl 11, 178-181.
54
Nociti, F.H., Jr., Machado, M.A., Stefani, C.M., and Sallum, E.A. (2001). Absorbable versus nonabsorbable
membranes and bone grafts in the treatment of ligature-induced peri-implantitis defects in dogs: a
histometric investigation. Int J Oral Maxillofac Implants 16, 646-652.
Park, J.B., Jeon, Y., and Ko, Y. (2015). Effects of titanium brush on machined and sand-blasted/acid-etched
titanium disc using confocal microscopy and contact profilometry. Clin Oral Implants Res 26, 130-136.
Parlar, A., Bosshardt, D.D., Cetiner, D., Schafroth, D., Unsal, B., Haytac, C., and Lang, N.P. (2009). Effects of
decontamination and implant surface characteristics on re-osseointegration following treatment of peri-
implantitis. Clin Oral Implants Res 20, 391-399.
Parma-Benfenati, S., Roncati, M., Galletti, P., and Tinti, C. (2015). Peri-implantitis Treatment with a
Regenerative Approach: Clinical Outcomes on Reentry. Int J Periodontics Restorative Dent 35, 625-636.
Persson, L.G., Araujo, M.G., Berglundh, T., Grondahl, K., and Lindhe, J. (1999). Resolution of peri-
implantitis following treatment. An experimental study in the dog. Clin Oral Implants Res 10, 195-203.
Persson, L.G., Ericsson, I., Berglundh, T., and Lindhe, J. (1996). Guided bone regeneration in the treatment
of periimplantitis. Clin Oral Implants Res 7, 366-372.
Persson, L.G., Ericsson, I., Berglundh, T., and Lindhe, J. (2001). Osseintegration following treatment of
peri-implantitis and replacement of implant components. An experimental study in the dog. J Clin
Periodontol 28, 258-263.
Renvert, S., Polyzois, I., and Maguire, R. (2009). Re-osseointegration on previously contaminated surfaces:
a systematic review. Clin Oral Implants Res 20 Suppl 4, 216-227.
Roccuzzo, M., Bonino, F., Bonino, L., and Dalmasso, P. (2011). Surgical therapy of peri-implantitis lesions
by means of a bovine-derived xenograft: comparative results of a prospective study on two different
implant surfaces. J Clin Periodontol 38, 738-745.
Sanz, M., Chapple, I.L., and Working Group 4 of the, V.E.W.o.P. (2012). Clinical research on peri-implant
diseases: consensus report of Working Group 4. J Clin Periodontol 39 Suppl 12, 202-206.
Schou, S., Holmstrup, P., Jorgensen, T., Skovgaard, L.T., Stoltze, K., Hjorting-Hansen, E., and Wenzel, A.
(2003a). Implant surface preparation in the surgical treatment of experimental peri-implantitis with
autogenous bone graft and ePTFE membrane in cynomolgus monkeys. Clin Oral Implants Res 14, 412-
422.
Schou, S., Holmstrup, P., Jorgensen, T., Stoltze, K., Hjorting-Hansen, E., and Wenzel, A. (2003b).
Autogenous bone graft and ePTFE membrane in the treatment of peri-implantitis. I. Clinical and
radiographic observations in cynomolgus monkeys. Clin Oral Implants Res 14, 391-403.
Schwarz, F., Becker, K., and Sager, M. (2015a). Efficacy of professionally administered plaque removal
with or without adjunctive measures for the treatment of peri-implant mucositis. A systematic review
and meta-analysis. J Clin Periodontol 42 Suppl 16, S202-213.
Schwarz, F., Jepsen, S., Herten, M., Sager, M., Rothamel, D., and Becker, J. (2006). Influence of different
treatment approaches on non-submerged and submerged healing of ligature induced peri-implantitis
lesions: an experimental study in dogs. J Clin Periodontol 33, 584-595.
Schwarz, F., John, G., and Becker, J. (2015b). Reentry After Combined Surgical Resective and Regenerative
Therapy of Advanced Peri-implantitis: A Retrospective Analysis of Five Cases. Int J Periodontics
Restorative Dent 35, 647-653.
Schwarz, F., Sahm, N., Bieling, K., and Becker, J. (2009). Surgical regenerative treatment of peri-implantitis
lesions using a nanocrystalline hydroxyapatite or a natural bone mineral in combination with a collagen
membrane: a four-year clinical follow-up report. J Clin Periodontol 36, 807-814.
Schwarz, F., Sahm, N., Iglhaut, G., and Becker, J. (2011a). Impact of the method of surface debridement and
decontamination on the clinical outcome following combined surgical therapy of peri-implantitis: a
randomized controlled clinical study. J Clin Periodontol 38, 276-284.
Schwarz, F., Sahm, N., Mihatovic, I., Golubovic, V., and Becker, J. (2011b). Surgical therapy of advanced
ligature-induced peri-implantitis defects: cone-beam computed tomographic and histological analysis. J
Clin Periodontol 38, 939-949.
55
Schwarz, F., Sahm, N., Schwarz, K., and Becker, J. (2010). Impact of defect configuration on the clinical
outcome following surgical regenerative therapy of peri-implantitis. J Clin Periodontol 37, 449-455.
Shibli, J.A., Martins, M.C., Ribeiro, F.S., Garcia, V.G., Nociti, F.H., Jr., and Marcantonio, E., Jr. (2006). Lethal
photosensitization and guided bone regeneration in treatment of peri-implantitis: an experimental study
in dogs. Clin Oral Implants Res 17, 273-281.
Singh, G., O'Neal, R.B., Brennan, W.A., Strong, S.L., Horner, J.A., and Van Dyke, T.E. (1993). Surgical
treatment of induced peri-implantitis in the micro pig: clinical and histological analysis. J Periodontol 64,
984-989.
Tomasi, C., and Derks, J. (2012). Clinical research of peri-implant diseases--quality of reporting, case
definitions and methods to study incidence, prevalence and risk factors of peri-implant diseases. J Clin
Periodontol 39 Suppl 12, 207-223.
Wetzel, A.C., Vlassis, J., Caffesse, R.G., Hammerle, C.H., and Lang, N.P. (1999). Attempts to obtain re-
osseointegration following experimental peri-implantitis in dogs. Clin Oral Implants Res 10, 111-119.

Abstract (if available)

Abstract Background. Along with increased number of implants utilized in clinical practice, there has been a rise in the prevalence of biological complications, including peri-implantitis. Therefore, the availability of efficacious therapy for peri-implantitis is an important area of investigation. Though many therapies have been proposed for peri-implantitis, there is paucity of data documenting their efficacy and effectiveness. ❧ Material & Methods. The present case series provides a protocol, which will include mechanical + chemical implant surface decontamination, as well as regeneration. The protocol entailed removal of the prosthesis, whenever possible in order to allow the implants to remain submerged under flap during healing. Mucoperiosteal flap was elevated to gain access to exposed implant surfaces for thorough biofilm removal. Macroscopically visible mineralized biofilm was removed by titanium brush followed by air powder abrasion, using sodium bicarbonate powder. Exposed implants were carefully treated with hydrofluoric acid gel for 30 seconds, followed by careful evacuation and copious irrigation with sterile saline and thorough wiping with gauze soaked in saline. Autogenous bone shavings were harvested within the same surgical area and used to cover all implant surfaces. Anorganic bovine bone minerals (ABBM

Linked assets

University of Southern California Dissertations and Theses

Conceptually similar

PDF

3D volumetric changes of tissue contour after immediate implant placement with and without xenograft in the horizontal gap: a randomized controlled clinical trial

PDF

The effect of vertical level discrepancy of adjacent dental implants on crestal bone resorption: a retrospective radiographic analysis

PDF

Aggregatibacter actinomycetemcomitans oral infection: in vivo T cell immune responses and a novel bone-targeting conjugate to treat biofilm-mediated osteolytic infection

PDF

Local and systemic responses to craniofacial osteolytic defects in an animal model

PDF

The effect of crown dimensions & implant dimensions on peri-implant marginal bone loss: a retrospective analysis

PDF

Effects of air polishing for the treatment of peri-implant diseases: a systematic review and meta-analysis

PDF

Periodontal regeneration utilizing antibody mediated osseous regeneration (AMOR): supra-alveolar critical sized defect model

PDF

Retrospective analysis of crestal bone changes on dental implant sites after a bone augmentation procedure: graft material comparisons

PDF

Healing of extraction sockets treated with anorganic bovine bone minerals: a micro-CT analysis

PDF

A randomized controlled clinical trial evaluating the efficacy of grafting the facial gap at immediately placed implants in the anterior maxilla: 3D analysis of bone and soft tissue changes

PDF

Alveolar ridge dimensional changes following ridge preservation procedure: CBCT linear analysis in non-human primate model

PDF

Dimensional changes in alveolar bone following extraction of maxillary molars in humans: a retrospective CBCT analysis

PDF

Three dimensional analysis of maxillary retromolar alveolar bone before and after en‐masse distalization

PDF

Influence of a novel self-etching primer on bond-strength to glass-ceramics and wettability of glass-ceramics

PDF

Orthodontic rotational relapse: prevalence and prevention

PDF

Effect of 0.25% sodium hypochlorite oral rinse and subgingival irrigation on periodontal clinical parameters

PDF

Patient reported outcomes measures (PROMs) and medication count of the three coronal advancement methods for the treatment of multiple gingival recession defects

PDF

Influence of enamel biomineralization on bonding to minimally invasive CAD/CAM restorations

PDF

An assessment of orthognathic surgery outcomes utilizing virtual surgical planning and a patented full-coverage 3D-printed orthognathic splint

Asset Metadata

Creator Sharifzadeh Boshehri, Navid (author)

Core Title Regenerative therapy for repair of peri-implantitis: Part I, Radiographic data on case series; Part II, Histologic report and clinical re-entry: case report

School School of Dentistry

Degree Master of Science

Degree Program Craniofacial Biology

Publication Date 07/28/2016

Defense Date 05/24/2016

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag biofilm,implants surface decontamination,OAI-PMH Harvest,peri-implant bone loss,peri-implantitis,Regeneration

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Zadeh, Homayoun (committee chair), Chen, Casey (committee member), Paine, Michael (committee member)

Creator Email naavidd@gmail.com,nsharifz@usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c40-284930

Unique identifier UC11280711

Identifier etd-Sharifzade-4662.pdf (filename),usctheses-c40-284930 (legacy record id)

Legacy Identifier etd-Sharifzade-4662-0.pdf

Dmrecord 284930

Document Type Thesis

Format application/pdf (imt)

Rights Sharifzadeh Boshehri, Navid

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the a...

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA