Received: 2 May 2023 | Revised: 28 June 2023 | Accepted: 21 August 2023

DOI: 10.1111/prd.12523

REVIEW ARTICLE

Selecting biomaterials in the reconstructive therapy of

peri-­implantitis

Alberto Monje1,2,3 | Ramón Pons2 | José Nart2 | Richard J. Miron3 | Frank Schwarz4 |
Anton Sculean3
1
Department of Periodontology and Oral Medicine, University of Michigan, Ann Arbor, Michigan, USA
2
Department of Periodontology, Universitat Internacional de Catalunya, Barcelona, Spain
3
Department of Periodontology, University of Bern, Bern, Switzerland
4
Department of Oral Surgery and Implantology, Goethe University, Frankfurt, Germany

Correspondence
Alberto Monje, Department of Periodontology, Universitat Internacional de Catalunya, C/ Josep Trueta s/n, 08195 -­Sant Cugat del Vallès, Barcelona, Spain.
Email: [email protected]

1 | I NTRO D U C TI O N aerobic bacteria. The therapeutic modality relies primarily upon

implant position, soft tissue characteristics, and defect configura-
Peri-­implantitis is a plaque-­mediated inflammatory condition char- tion. Nonsurgical measures have been shown to be unsatisfactory
acterized by progressive bone loss. In fact, local predisposing, pre- in terms of disease resolution.6 Hence, surgical strategies are often
cipitating, and acceleratory factors were demonstrated to be key necessary. This therapeutic option demonstrated enhanced predict-
in understanding the site-­specific prevalence of this disorder.1 This ability and effectiveness levels in the long-­term stability of the peri-­
entity jeopardizes the longevity of dental implants, thus negatively implant hard and soft tissues.7
impacting the quality of life of patients. Moreover, peri-­implantitis is In general, peri-­implantitis bone defects exhibiting contained de-
suggested to lead to an increased systemic status of inflammation. 2,3 fects are prone to show favorable reconstructive/regenerative out-
This may increase an individual's susceptibility to life-­threatening comes together with a consistent reduction in the pocket depth.8,9
conditions. 2 Therefore, peri-­implant infections must be promptly On the other hand, noncontained defects are discouraged from ap-
diagnosed and eliminated. plying the principles of bone regeneration by means of using bone
Several options are recommended to relieve the inflammation substitutes and/or barrier membranes. Despite these indications,
and remove the infection. Accordingly, implant removal or ther- the benefit provided by biomaterials in the reconstructive manage-
apeutic maneuvers to establish a healthy ecosystem in the peri-­ ment of peri-­implantitis bone defects remains unclear. Therefore,
implant environment have been suggested.4 While the former has the aim of this narrative review is to address major clinical concerns
been proven to be more predictable, the latter has been shown to be regarding the effectiveness and plausibility of using biomaterials in
more conservative. Indeed, implant removal is commonly associated peri-­implantitis therapy.
with regenerative procedures of the alveolar bone deformity that
often demand time and are more costly.5 Disease severity, implant
expendability for biomechanical reasons, or esthetic demand seem 2 | C R ITE R I A TO S U CC E E D I N
to be a few of the leading aspects in the decision-­making process PE R I -­I M PL A NTITI S TH E R A PY
on maintaining or extracting implants showing peri-­implant lesions.
Peri-­implantitis is an inflammatory disorder and the primary The objective in the management of peri-­implantitis is to create an
endpoint in the management of this disorder is a condition of health environment that is manageable by both the patient and the clini-
characterized by shallow pockets with a dominant population of cian. This is achieved by reducing the probing pocket depth (PPD)

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2023 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd.

192 | 
wileyonlinelibrary.com/journal/prd Periodontology 2000. 2024;94:192–212.
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MONJE et al. 193

to ≤5 mm. As a result, bleeding on probing (BOP) and suppuration the goal is to reduce the PPD by augmenting peri-­implant bone
(SUP) are conditioned to be dropped/eliminated. Furthermore, support. Moreover, patient satisfaction must also be incorporated
progressive bone loss should be arrested when inflammation is within the success criteria. In this sense, mucosal recession (MR)
resolved. Regardless of the type of surgical intervention, even in occurs as part of the resolution of inflammation.10 Therefore, con-
reconstructive procedures, the primary endpoint for disease man- cerns related to aesthetics must be underlined when delivering
agement is to reduce the PPD. In fact, in reconstructive procedures, the treatment plan, as it may interfere with patient satisfaction.

F I G U R E 1 Reconstructive therapy is indicated in scenarios exhibiting intrabony compartments. On the left side, reconstructive therapy
of a 3-­wall defect where surface decontamination and bone regeneration are indicated to enhance the support while reducing the pocket
depth. On the right side, a combined defect. A combined therapeutic modality including implantoplasty for the supra-­crestal component is
recommended to reduce pocket depth as a consequence of intentional mucosal recession in the supra-­crestal component and bone gain in
the intrabony compartment.
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194 MONJE et al.

3 | LI M ITATI O N S I N PE R I - ­I M PL A NTITI S major factors are to be considered: soft tissue characteristics,

TH E R A PY prosthesis design, or implant position in a three-­dimensional
perspective.14
The dominant factors that dictate a hopeless prognosis and where, • Impossibility to decontaminate the implant surface due to charac-
therefore, implant removal is indicated are the following: teristics related to defect configuration or to the armamentarium
available by the operator. A broad variety of strategies have been
• A patient's unwillingness to enroll in a professionally administered used for implant surface decontamination. Mechanical methods
maintenance program and inadequate motivation to perform self-­ have been demonstrated to be effective in eliminating calculus
performed oral hygiene measures for plaque control. Lack of sup- deposits and residual debris; however, the presence of undercuts
portive care was demonstrated to be one indicator of therapeutic and the grooves and porosities along the implant surface make
failure (OR = 5).11 it difficult to achieve an aseptic surface. Hence, in conjunction
• Implants exhibiting advanced peri-­implant bone loss. Studies with mechanical methods, the use of chemical adjuncts has been
have demonstrated a significantly lower likelihood of success in suggested to dilute bacterial concentrations and to eliminate en-
the surgical management of peri-­implantitis if the lesions extend dotoxins. Moreover, pharmacological adjuncts have also been rec-
≥50% of the implant length.11,12 In fact, baseline advanced bone ommended to diminish the bacterial load. Other strategies, such
loss is linked to therapeutic failure (OR = 20).13 as use of lasers, implantoplasty (in particular for areas outside the
• Impossibility of addressing local factors associated with the reparative potential/bony envelope) and electrolysis, have been
14
onset of disease. Identifying and modifying local predispos- advised for implant surface decontamination to promote peri-­
ing factors is key in preventing recurrence. Among them, three implant health.15

TA B L E 1 Indications of defect configurations for reconstructive therapy and clinical recommendations.

Defect
configuration
(Monje et al.
2019) Illustration Radiographic image Intraoperative image Clinical recommendation

Class Ib Check bucco-­lingual implant position to

understand the reparative potential

Class Ic Accommodate decontamination methods

according to the defect entrance

Class IIIb Evaluate the adjacent bony peaks and

the bucco-­lingual implant position to
assess the reparative potential

Class IIIc Evaluate the adjacent bony peaks to

assess the reparative potential
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MONJE et al. 195

• Expendable implants due to their inadvertent biomechanical, of interproximal support and/or implants in an inadequate posi-
functional, or esthetic role can be removed regardless of the ex- tion that lead to deficient restorations have a more unfavorable
tent of the disease. prognosis.16
• Implants exhibiting peri-­implantitis in the anterior maxillary area
and demand esthetic outcomes. In general, implants presenting On the other hand, patient's willingness and commitment to
moderate or advanced peri-­implantitis lesions and/or with a lack manage the disorder is important to be assessed. In this sense, the

TA B L E 2 Severity of peri-­implantitis bone defects.

Severity (Monje et al.

2019) Clinical image Radiographic image Intraoperative image

Slight (MBL <25%)

Moderate (MBL
25–­50%)

Advanced (MBL >50%)

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196 MONJE et al.

TA B L E 3 Efficacy of surgical reconstructive therapy of peri-­implantitis.

Defect Healing protocol

Study Follow-­up N patients N patients/ configuration Decontamination (submerged/
Author (year) design (months) (total) group (sites) Intervention (number of walls) strategy transmucosal) Bone graft

Aghazadeh et al. RCT 72 39 16 (25) Reconstructive 2, 3 and Ti curettes +3% Transmucosal/ AB

(2022)9 therapy circumferential Hydrogen nonsubmerged
23 (38) DBBM
peroxide +
Saline

Derks et al. MRCT 12 138 67 (68) OFD Circumferential Ti curettes + Ti Transmucosal/ —­

(2022)29 brushes + nonsubmerged
69 (69) Reconstructive DBBMC
Saline
therapy

Hamzacebi et al. RCT 6 19 9 (19) OFD 2, 3, and Ti brush + CA or Transmucosal/ —­

(2015)57 circumferential Tetracycline nonsubmerged
10 (19) Reconstructive —­
HCL + Saline
therapy

Isehed et al. RCT 72 29 14 (14) OFD Angular defect (not US + Ti Transmucosal/ —­

(2018)28 specified) instruments + nonsubmerged
15 (15) Reconstructive —­
NaCl
therapy

Jepsen et al. MRCT 12 63 30 (30) OFD Circumferential Ti brushes +3% Transmucosal/ —­

(2016)21 Hydrogen nonsubmerged
33 (33) Reconstructive PTGs
peroxide +
therapy
Saline

Polymeri et al. RCT 12 24 11 (11) Reconstructive 3 Ti curettes +3% Transmucosal/ DBBM

(2020)74 therapy Hydrogen nonsubmerged
13 (13) HA
peroxide +
Saline

Renvert et al. RCT 12 41 20 (20) OFD 3 and 4 Ti curettes +3% Transmucosal/ —­

(2018)75 Hydrogen nonsubmerged
21 (21) Reconstructive HA
peroxide +
therapy
Saline

Renvert et al. MRCT 12 66 32 (32) OFD Circumferential Ti brushes + Ti Transmucosal/ —­

(2021)22 (270°) curettes +3% nonsubmerged
34 (34) Reconstructive DBBM
Hydrogen
therapy
peroxide +
Saline

Schwarz et al. CS 6 22 11 (11) Reconstructive Semi/or Plastic curettes + Transmucosal/ HA

(2006)53 therapy circumferential Saline nonsubmerged
11(11) DBBM

Wohlfahrt et al. RCT 12 32 16 (16) OFD 1,2 and 3 Ti curettes +24% Submerged —­
(2012)26 EDTA gel +
16 (16) Reconstructive PTGs
Saline
therapy

Abbreviations: AB, autogenous bone graft; CS, case series; DBBM, deproteinized bovine bone mineral; DBBMC, deproteinized bovine bone mineral
collagen, HA, hydroxyapatite/tricalcium phosphate; EMD, enamel matrix derivative protein; MRCT, multicenter randomized controlled clinical trial;
OFD, open flap debridement; PRF, platelet-­rich fibrin; PTGs, porous titanium granules; RCT, randomized controlled clinical trial; Ti, titanium.

sequelae led by implant removal and the added outlay associated Schwarz et al.8 tested the effectiveness of reconstructive therapy
with implant-­site development interventions and prosthesis rehabil- by means of anorganic bovine bone and collagen membrane in
itation must be thoroughly communicated. three different scenarios, including buccal dehiscence + semicir-
cumferential defects, buccal dehiscence + circumferential defects,
or pure circumferential intrabony defects. At the 6-­month follow-
4 | I N D I C ATI O N S FO R R ECO N S TRU C TI V E ­up, significant differences were noted in the PPD (mean difference
TH E R A PY approximately 1 mm) and clinical attachment level (mean differ-
ence approximately 1 mm), favoring the defects exhibiting a pure
In general, contained defects are prone to show favorable recon- circumferential configuration. Similarly, Aghazadeh et al.9 explored
8
structive outcomes when managed by means of regeneration. the influence of defect features on reconstructive outcomes when
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MONJE et al. 197

Probing Bleeding
depth score Suppuration Mucosal Radiographic Disease
Barrier reduction reduction reduction recession bone gain resolution Confounders of disease
membrane Biologic Antibiotics (mm) (%) (%) (mm) (mm) (%) resolution

RCM —­ Azithromycin 250 mg 1.7 55.6 NR NA 0.7 (−) 36.0 • Number of

2/Day 5d reinstrumentations during,
2.8 50.6 NR 1.6 78.3
follow-­up period
• Current smokers

—­ —­ Amoxicillin 750 mg 3.7 49.6 NR 1.1 1.1 13.5 • Severity of peri-­implantitis of

2/Day 10d the included patients
—­ 3.7 44.8 NR 0.7 1.1 16.4

—­ —­ Metronidazole 2.0 44.0 NR 0.2 (−) NA NA • Absence of demographic data

500 mg 3/Day 7d analysis
—­ PRF 2.8 54.0 NR 0.5 NA NA
• Absence of radiographic
analysis
• No postoperative
professional prophylaxis

—­ —­ —­ NA 27.5 43 NA 1.3 NA • Absence of periodontal

records
—­ EMD NA 10 60 NA 1.4 NA
• Absence of demographic data
analysis

—­ —­ Amoxicillin 500 mg 2.6 45.4 24.6 NA 1.0 23.0 • History of periodontitis

3/day and • Current smokers
—­ 2.8 56.1 26.8 3.6 30.0
Metronidazole • Implant brand
400 mg 2/Day 8d • Time interval recalls

—­ —­ Amoxicillin 500 mg 3.6 55.5 79.5 NA 2.5 18.0 • History of periodontitis

3/day and
3.7 50.0 84.6 3.0 0.0
Metronidazole
500 mg 2/Day 8d

—­ —­ Azithromycin 500 mg 2.5 65.0 NR 0.2 0.2 5.0 • Peri-­implant defect

1 day and 250 mg morphology
—­ 3.6 52.4 NR 0.2 0.7 42.9
1/Day 2–­4 d • DM
• Implant brand

—­ —­ Azithromycin 500 mg 2.3 1.0 (mBI)* 1.3 (±1.7) 0.9 1.1 NA • History of periodontitis or
1 day and 250 mg active periodontitis
RCM 1.9 0.9 (mBI)* 1.5 (±1.3) 0.5 2.3 NA
1/Day 2–­4 d • Implant brand

—­ —­ —­ 2.1 52.0 NR 0.3 NA NA • Absence of radiographic

measurement analysis
RCM 2.6 50.0 NR 0.3 NA NA
• Short follow-­up

—­ —­ Amoxicillin 500 mg 2.0 56.0 NR NA 14.8 (%) NA • Current smokers

3/day and • History of periodontitis
—­ 1.7 38.0 NR NA 57.0 (%) NA
Metronidazole
400 mg 2/Day
10d

regeneration was applied by means of autologous or xenogeneic peaks that enhance support and continence to the bone graft are
bone. Circumferential and deeper defects showed more defect fill indicated for reconstructive therapy. Along these lines, it is fun-
at the 12-­month follow-­up than partially contained defects (2-­3-­wall damental to understand the existing limitations of reconstructive
defects). Monje et al.17 further showed the positive association be- therapy concerning defect configuration (Figure 1). In combined de-
tween baseline defect angle and radiographic bone gain. In fact, de- fects, it was described that the area of the implants outside the re-
fect angles <40° are more prone to show predictable and favorable parative potential is not indicated for reconstruction but rather for
reconstructive outcomes (radiographic bone gain). These findings resection. 20 Hence, in cases exhibiting areas above the apical-­most
are thus aligned with the existing evidence in periodontal tissue re- adjacent bony peak or outside the bony envelope, the reparative
generation.18,19 Therefore, bone defects presenting adjacent bony potential might be overestimated, which may lead to therapeutic
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198 MONJE et al.

TA B L E 4 Effectiveness of reconstructive therapy of peri-­implantitis

N N Healing protocol
Study Follow-­up patients patients Defect configuration (submerged/
Author (year) design (months) (total) (sites) Intervention (number of walls) Decontamination strategy transmucosal) Bone graft

Astolfi et al. RCS 24 to 96 28 14 (16) Reconstructive 2 and 3 Mini-­f ive curettes +3–­5% Transmucosal/ DBBM
(2021)76 therapy + Hydrogen peroxide nonsubmerged
maintenance +0.12% Chlorhexidine
of the + Implantoplasty
prosthesis

14 (16) Reconstructive
therapy +
removal
of the
prosthesis

de Tapia et al. RCT 12 30 15 (15) Reconstructive 2, 3 and 4 Plastic US +3% Hydrogen Transmucosal/ HA
(2019)77 therapy peroxide + Ti brush nonsubmerged

15 (15) Plastic US +3% Hydrogen

peroxide

Froum et al. RCS 36 to 180 38 38 (46) Reconstructive NR Ti curettes + Ti brushes + Transmucosal/ FDBA + DBBM
(2022)34 therapy Minocycline (50 mg/ nonsubmerged
mL) + Saline + AP + CA

La Monaca PCS 60 34 34 (34) Reconstructive NR Ti curettes + US + Ti Transmucosal/ FDBA

et al. therapy brush + AP + 3% nonsubmerged
(2018)35 Hydrogen peroxide
+0.12% Chlorhexidine
+ Tetracycline
hydrochloride + Saline

Mercado et al. PC 36 30 30 (30) Reconstructive Circumferential US +24% EDTA + Saline Transmucosal/ DBBMC + EMD +
(2018)33 therapy + nonsubmerged Doxycycline
CTG (esthetic 100 mg
zone)

Monje et al. PCS 12 15 15 (27) Reconstructive 2 and 3 Mini-­f ive and Gracey Submerged DBBM + AB
(2020) 49 therapy curettes +
Implantoplasty +3%
Hydrogen peroxide
+0.12% Chlorhexidine

Nart et al. PCS 12 13 13 (17) Reconstructive 2 and 3 Stainless steel curettes Transmucosal/ 50% vancomycin
(2018) 46 therapy + Implantoplasty + nonsubmerged FDBA +50%
US +3% Hydrogen tobramycin
peroxide + Saline FDBA

Pilenza et al. RCS 12 11 11 (20) Reconstructive NR AP + 11 mg Transmucosal/ HA + EMD

(2022)78 therapy Povidone-­iodine/ml nonsubmerged

Roccuzzo et al. PCS 60 51 51 (51) Reconstructive 2, 3 and 4 Ti curettes + Ti brushes Transmucosal/ DBBMC
(2021)36 therapy +24% EDTA +1% nonsubmerged
Chlorhexidine gel

Roos-­Jansåker PCS 12 12 12 (16) Reconstructive NR Ti instruments +3% Submerged NBDBS

et al. therapy Hydrogen peroxide +
(2007)31 Saline

Schwarz et al. PCS 12 27 27 (27) Reconstructive Semicircumferential Carbon curettes + Saline Transmucosal/ DBBM
(2010) 8 therapy (Class Ib) b nonsubmerged

Circumferential
(Class Ic) b

Circumferential
(Class Ie) b

Wang et al. RCT 6 24 12 (12) Reconstructive 2, 3, and Piezoelectric + Stainless Transmucosal/ FDBA
(2021)79 therapy circumferential steel scalers + nonsubmerged
Implantoplasty

12 (12) Piezoelectric + Stainless

steel scalers + Er:YAG
laser + Implantoplasty
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MONJE et al. 199

Probing
depth Bleeding Suppuration Mucosal Radiographic Disease
Barrier reduction score reduction recession bone gain resolution
membrane Biologic Antibiotics (mm) reduction (%) (%) (mm) (mm) (%) Confounders of disease resolution

RCM —­ Amoxicillin 875/125 mg + NR 70.0 95.0 NA 2.8 NR • Absence of demographic data

Metronidazole • No postoperative professional
250 mg 3/Day 7d prophylaxis

NR 58.3 83.3 NA 2.1 NR

RCM —­ Amoxicillin 500 mg + 3.8 80.0 40.0 0.4 2.6 66.7 • Current smokers
Metronidazole • Disparity between groups at
500 mg 3/Day 7d baseline
2.5 54.0 23.0 0.6 1.1 23.1
• No postoperative professional
prophylaxis
• Short follow up

RCM PDGF or Amoxicillin 500 mg 3/ 6.7 23.0 NA 0.9 (−) 3.6 NA • Absence of group control
EMD Day 7d • Highly variable follow-­up
• Unclear material and methods
• Peri-­implant defect configuration

RCM -­ Amoxicillin/clavulanic 1.3 58.9 NR NA 0.4 58.8 • Peri-­implant defect configuration

acid 875/125 mg +
Metronidazole
250 mg 3/Day 10d

CTG EMD -­ 5.4 80 80.0 0.1 4.3 56.6 • Peri-­implant defect configuration
• Addition of CTG in some cases
• Strict SPT

RCM —­ Amoxicillin 750 mg 2/ 3.7 1.6 (mBI)a 59.2 2.5 2.2 85.2 • Peri-­implant defect configuration
Day 7d • Absence of control group
• Short follow up

RCM —­ —­ 4.2 70.6 88.2 1.3 3.7 70.6 • Absence of control group
• Short follow up
• Small sample size
• Implant brand

—­ EMD Amoxicillin 375 mg + 2.2 70.0 65.0 NA 1.1 75.0 • Current smokers
Metronidazole • Absence of control group
250 mg 3/Day 8d • Absence of PPD measurement

CTG (if —­ Amoxicillin/clavulanic 2.8 53.4 23.5 0.7 NA 45.3 • Implant brand (one)
needed) acid 1gr/200 mg 2/ • Absence of radiographic
Day 6d measurement analysis

RCM —­ Amoxicillin 375 mg 3/ 4.2 67.7 NR 2.8 2.3 NR • Absence of control group
day + Metronidazole • Small sample size
400 mg 2/Day 10d • No postoperative professional
prophylaxis

RCM —­ —­ 1.6 38.9 NA 0.4 NA NA • Absence of demographic data

• Absence of radiographic
measurement analysis
1.6 25.9 0.5

2.7 61.1 0.3

ADM -­ Amoxicillin 500 mg 2/ 1.8 39.0 NR NR 1.0 NA • Short follow up

Day 10d • Small sample size
• No postoperative professional
prophylaxis
2.6 31.0 1.2

(Continues)
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200 MONJE et al.

TA B L E 4 (Continued)

N N Healing protocol
Study Follow-­up patients patients Defect configuration (submerged/
Author (year) design (months) (total) (sites) Intervention (number of walls) Decontamination strategy transmucosal) Bone graft

Wen et al. PS 8 22 22 (32) Reconstructive Circumferential Implantoplasty + Glycine Submerged FDBA + DBBM
(2021)70 therapy AP + Tetracycline + AB
(250 mg/2.5 cc)

Wiltfang et al. PCS 12 22 22 (36) Reconstructive NR Curettes + Diamonds Transmucosal/ DBBM + AB

(2012)32 therapy + Implantoplasty + nonsubmerged
Etching gel

Yamamoto PCS 12 12 12 (12) Reconstructive 2, 3, and Er:YAG laser Transmucosal/ DBBM

et al. therapy circumferential nonsubmerged
(2021)50

Abbreviations: AB, autogenous bone; ADM, absorbable acellular dermal matrix; AP, air-­powder abrasive; CA, citric acid; CTG, connective tissue
graft; DBBM, deproteinized bovine bone mineral; DBBMC, deproteinized bovine bone mineral collagen, HA, hydroxyapatite/tricalcium phosphate;
dPTFE, titanium reinforced nonresorbable dense polytetrafluoroethylene; EDTA, 24% ethylenediaminetetraacetic acid; EMD, enamel matrix
derivative protein; FDBA, freeze-­dried bone allograft; NA, not assessed; NBDBS, nonbovine-­derived bone substitute; NR, not reported; PC,
prospective cohort study; PCS, prospective case series; PS, prospective controlled study; RCM, resorbable collagen membrane; RCS, retrospective
case series; RCT, randomized controlled clinical trial; Ti, titanium; US, ultrasonic scaler device.
a
Modified sulcular bleeding index (mBI) (Mombelli et al. 1987).
b
Defect configuration classification (Schwarz et al. 2007).

failure. Accordingly, reconstructive therapy would be indicated in approach compared to open flap debridement (OFD) at 12 months.
the following bone defect configurations (Tables 1 and 2): A significant effect of radiographic bone gain was demonstrated for
the sites reconstructed, while clinical improvements were equal for
• Class Ib: 2/3-­wall defect where in case of implants positioned too both groups. The 7-­year follow-­up examination, 27 however, showed
buccally, only the area inside the alveolar envelope is aimed at progressive bone loss for both groups, leading to therapeutic fail-
being reconstructed. ure. Jepsen et al. 21 compared the use of titanium granules for re-
• Class Ic: Circumferential defect (4-­wall defect) constructive therapy and OFD in a multicenter 12-­month follow-­up
• Class IIIb: 2–­3 walls defect + supra-­crestal defect where in case study of 3-­4-­wall intrabony defects applying transmucosal healing.
of implants positioned too buccally, only the area inside the alve- The reconstructive group outperformed in the radiographic bone
olar envelope and below the adjacent bony peak is aimed at being fill; nonetheless, PPD and BOP reduction were similar, leading to an
reconstructed. even disease resolution rate. Isehed et al. 28 compared enamel matrix
• Class IIIc: Circumferential defect (4-­wall defect) + supra-­crestal derivatives (EMD) to OFD of angular peri-­implant bone defects at
defect where only the area below the adjacent bony peak is aimed the 60-­month follow-­up. It was shown that radiographic bone level
at being reconstructed. was superior in sites managed by means of reconstructive therapy
(mean difference approximately 1 mm). Nevertheless, no significant
Moreover, it is known that regenerative therapy in smokers often differences were noted in the evaluated clinical parameters. Renvert
leads to undesired outcomes due to the altered immunologic and an- et al. 22 performed a 12-­month RCT to assess the effect of recon-
giogenic response that negatively impacts osteogenic activity. Thus, structing ≥3-­wall defects with xenografts compared to OFD. The
in smokers, particularly heavy smokers (≥10 cig/day), this interven- radiographic bone level was significantly higher in the test group.
tion would not be indicated. The BOP rate was significantly higher at the control sites. In fact, dis-
ease resolution was lower in the control group (5%) than in the test
group (42%). Derks et al. 29 in a 12-­month multicenter study tested
5 | E FFI C AC Y O F R ECO N S TRU C TI V E the effect of grating by means of xenograft with 10% collagen of
TH E R A PY ≥3-­4-­wall defects following a transmucosal healing approach when
compared to OFD. It was demonstrated that reconstructive therapy
Multiple clinical trials have validated this approach alone21–­23 or in did not offer benefit in terms of radiographic bone gain or clinical
combination with other measures, such as implantoplasty24,25 com- parameters but a significant reduction in MR. 29 Hence, in general,
bined with defects exhibiting supra-­crestal components. It is worth reconstructive therapy showed conflicting outcomes. The limited
stating that randomized clinical trials (RCTs) are sparse. Wohlfahrt evidence together with the uneven methodologies concerning the
et al. 26 tested the impact of bone grafting with titanium granules of reconstructive bone substitute and surface decontamination strate-
intrabony defects ≥4 mm in depth by applying a submerged healing gies preclude strong conclusions (Table 3).
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MONJE et al. 201

Probing
depth Bleeding Suppuration Mucosal Radiographic Disease
Barrier reduction score reduction recession bone gain resolution
membrane Biologic Antibiotics (mm) reduction (%) (%) (mm) (mm) (%) Confounders of disease resolution

dPTFE —­ Amoxicillin 500 mg 2.9 63.3 NR NA 3.4 NA • Short follow up

3/Day 10d or • Current smokers
Azithromycin • History of periodontitis
250 mg 2/Day 3 days

—­ —­ Ampicillin/sulbactam 4.0 36.0 72.0 1.3 3.5 NA • No prosthesis removal during

1.5gr i.v. or surgery
Clindamycin 600 mg • Unclear radiographic
(prophylactic) measurement analysis
• Absence of demographic data

-­ -­ -­ 3.2 41.0 NR NR 26.3 (%) 50.0 • Short follow up

• Unknown SPT
• Absence of control group
• Absence of demographic data

F I G U R E 2 Schematic illustration of the cellular and molecular events of the inflammatory cascade during peri-­implant regeneration in
reconstructive therapy of peri-­implantitis.
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202 MONJE et al.

F I G U R E 3 Cellular stages of
regeneration after reconstructive therapy
of peri-­implantitis.

F I G U R E 4 Histologic images at 4-­and 24-­week follow-­up of a created alveolar bone defect reconstructive by means of xenograft and a
sugar-­based collagen matrix (Ossix Volumax, Datum Dental, Lod, Israel). Note the ossifying potential of the matrix, while excluding epithelial
cells from the grafted area.

F I G U R E 5 Scanning electron microscopy (SEM) of a bovine-­derived particle (Inteross, SigmaGraft, CA, USA) at different magnifications
(×30, ×50 and ×1000).

6 | E FFEC TI V E N E S S O F R ECO N S TRU C TI V E grafting infra-­osseous bone defects by means of tricalcium phosphate
TH E R A PY and nonresorbable barrier membranes after surface decontamination
with a CO2 laser or air-­powder abrasive device in a 60-­month follow-
Understanding the paucity of data derived from RCTs, it is critical ­up study. The radiographic bone level was approximately 2 mm higher
to further assess the effectiveness of reconstructive therapy dem- than the preoperative level. Likewise, Roos-­Jansaker et al.31 evalu-
30
onstrated in cohort studies. Deppe et al. analyzed the effect of ated the effectiveness of grafting peri-­implant bone defects with a
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MONJE et al. 203

F I G U R E 6 Scanning electron
microscopy (SEM) of a synthetic material
(tricalcium phosphate) (Bone Sigma
TCP, SigmaGraft, CA, USA) at different
magnifications (x30, x50, and x1000).

F I G U R E 7 Scanning electron
microscopy (SEM) of a collagen-­
based resorbable barrier membrane
(InterCollagen Guide, SigmaGraft, CA,
USA) at different magnifications (×800,
×1600, ×1600, and ×3200).

F I G U R E 8 Scanning electron
microscopy (SEM) cross-­sectional view
of a sugar-­based cross-­linking barrier
membrane (Ossix Plus, Datum Dental,
Lod, Israel) at different magnifications
(200× and 13 000×).

nonbovine-­derived bone substitute and a barrier membrane after 2.5 mm in PPD with a clinical bone fill/gain of approximately 2.5 mm,
decontaminating the surface with 3% hydrogen peroxide by apply- which varies according to the defect configuration. Wiltfang et al.32
ing a submerged approach in a 12-­month study. PPD was significantly in a prospective 12-­month follow-­up case series demonstrated the
reduced by 4.2 mm, and a defect fill of 2.3 mm was reported. Similarly, effectiveness of reconstructive therapy using autogenous bone and a
Schwarz et al.8 using a combination of anorganic bovine bone with a xenograft in an equal ratio after decontaminating the implant surface
collagen membrane showed an average reduction of approximately by means of etching gel. In fact, radiographic bone gain of 3.5 mm with
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204 MONJE et al.

TA B L E 5 Comparative studies testing the effect of barrier membranes in reconstructive therapy for peri-­implantitis.

N N Defect Healing protocol

Study Follow-­up patients patients configuration Decontamination (submerged/ Bone
Author (year) design (months) (total) (sites) Intervention (number of walls) strategy transmucosal) graft Barrier membrane

Isler et al. RCT 36 51 25 (25) Reconstructive 2, 3 and 4 Ti curettes + Transmucosal/ DBBM CGF
(2022)58 therapy Saline nonsubmerged
26 (26) RCM

Monje et al. RCT 12 33 17 (24) Reconstructive 2, 3 and 4 Ti brushes +3% Transmucosal/ DMCA —­
(2023)17 therapy Hydrogen nonsubmerged
16 (24) RCM
peroxide +
Saline

Regidor et al. RCT 12 43 22 (22) Reconstructive 1, 2, 3, and 4 Ti curettes + Ti Transmucosal/ DBBMC —­

(2023)68 therapy brushes + nonsubmerged
21 (21) RCM
Saline

Roos-­Jansåker RCT 72 25 12 (22) Reconstructive 2, 3 and 4 3% Hydrogen Transmucosal/ HA -­

et al. therapy peroxide + nonsubmerged
13 (23) (PGA/PLABM)
(2014)66 Saline

Schwarz et al. CS 48 20 11 (11) Reconstructive Semi/or Plastic curettes + Transmucosal/ DBBM RCM
(2009) 80 therapy circumferential Saline nonsubmerged
9 (9) HA

Abbreviations: CGF, concentrated growth factor; CS, case series; DBBM, deproteinized bovine bone mineral; DBBMC, deproteinized bovine bone
mineral collagen, HA, hydroxyapatite/tricalcium phosphate; DMCA, Demineralized and mineralized cortical allograft; NA, not assessed; NR, not
reported; PGA/PLABM, pga/pla barrier membrane; RCM, resorbable collagen membrane; RCT, randomized controlled clinical trial; SPT, Supportive
periodontal therapy; Ti, titanium.
a
Modified sulcular bleeding index (mBI) (Mombelli et al. 1987).81
b
Suppuration Index (Monje et al. 2020).82

an average reduction of PPD of 4 mm was shown. Mercado et al.33 Autogenous bone is derived from the same individual and therefore
reported the therapeutic outcome at the 36-­month follow-­up using provides osteoconductivity (scaffold), osteoinductivity (growth fac-
EMD and inorganic bovine bone with 10% collagen. At the latest ex- tors), and osteogeneicity (mesenchymal cells). In this sense, it was
amination, it was noted that PPD reduction and radiographic bone identified that cortical bone chips supply 43 growth factors, such as
gain amounted to ∼5 and ∼3 mm, respectively.34 In a longitudinal TGF-­β1, TGF-­β2, BMP, and OSF-­1, which are all critical in bone for-
study, Froum & Kim assessed the clinical and radiographic bone levels mation.37 To reduce morbidity associated with a secondary harvest-
of advanced peri-­implantitis defects managed by means of platelet-­ ing site, other biomaterials have been advocated. Xenogeneic grafts,
derived growth factor (PDGF) or EMD and a mixture of anorganic particularly anorganic bovine bone, have been extensively studied
bovine bone and mineralized allograft. PPD was subjected to sig- (Figure 5). It is a deproteinized, sterilized, slowly resorbable bovine
nificant reduction (6.7 mm) and bone level gain (3.6 mm) at the latest cancellous bone. It was demonstrated that topographic features pro-
follow-­up. In terms of survival, La Monaca et al.35 in a 60-­month study mote blood clot stabilization, and interconnected channels stimulate
showed a 100% survival rate, achieving 59% disease resolution. Inter- cell migration.38 Accordingly, its function is merely osteoconductive.
36
estingly, Roccuzzo et al. in a 60-­month study on 51 patients agreed On the other hand, allogeneic grafts are sourced from human ca-
on these findings. A relatively high implant survival rate of 80% was davers, and according to the preservation process, they may or may
shown in patients who adhered to supportive maintenance care. Of not provide osteoinductive potential.39 In general, demineralized
these patients, 45% demonstrated disease resolution. Hence, based grafts are prone to display osteoinductivity as they preserve bone
on existing cohort and case report studies, reconstructive therapy is morphogenetic proteins (BMP).40 In particular, BMP-­2 and BMP-­9
suggested to be safe and effective in terms of PPD reduction, disease have been shown to orchestrate the modulation and differentiation
resolution, marginal bone level gain and implant survival (Table 4). of mesenchymal cells into bone-­forming cells.41–­43 Regardless of the
nature, the turnover of allogeneic grafts is, in general, significantly
faster when compared to xenografts, resulting in a lower rate of
7 | S I G N I FI C A N C E O F B O N E G R A F TI N G residual particulated graft of the former.44 Synthetic materials are
M ATE R I A L biocompatible bone fillers that, ideally, should show minimal fibrotic
reactions and undergo remodeling while supporting new bone for-
The use of bone grafting materials in the reconstructive therapy mation (Figure 6).45 Interestingly, in peri-­implantitis therapy, porous
of peri-­implantitis was empirically adopted from interventions re- titanium granules as synthetic material were suggested to support
lated to bone regeneration of periodontal defects (Figures 2–­4). the process of reosseointegration. 21
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MONJE et al. 205

Probing
depth Bleeding Mucosal Radiographic
reduction score Suppuration recession bone gain Disease Confounders of disease resolution
Biologic Antibiotics (mm) reduction (%) reduction (%) (mm) (mm) resolution (%) (bullets)

-­ Amoxicillin 500 mg and 2.1 56.8 NR 0.3 1.4 26.9 • Number of reinstrumentations
Metronidazole during follow-­up period
2.1 61.8 NR 0.4 1.7 34.6
500 mg 3/Day 7d • History of periodontitis
• Current smokers

—­ Amoxicillin 750 mg 2/ 4.0 1.49 (mBI)a 0.56 (±0.65) b 0.13 1.7 79.2 • Strict adherence to SPT
Day 7d a b • Contained defects within bony
3.4 1.50 (mBI) 0.56 (±0.66) 0.25 1.7 75.1
housing

—­ Amoxicillin 750 mg 2/ 4.2 66.2 16.6 0.1 0.9 45.0 • Number of reinstrumentations
Day 10d during follow-­up period
4.5 68.4 48.8 0.2 1.4 36.8
• Time interval recalls
• Peri-­implant defect morphology

-­ Amoxicillin 375 mg 3.3 82.9 22.7 2.0 1.1 51.1 • Disparity between groups at
3/day and baseline
3.0 42.3 19.9 1.3 1.3 51.1
Metronidazole • Current smokers
400 mg 2/Day 10d • History of periodontitis

-­ -­ 2.5 51.0 NR 0.5 NA NA • Implant brand

• Peri-­implant defect morphology
1.1 32.0 NR 0.4 NA NA
• Absence of radiographic
measurement analysis

Several bone substitutes have been tested in this therapeutic combined with a collagen barrier membrane in a 6-­m onth case se-
modality, with xenografts and allografts being the most explored. ries study. Comparable outcomes were achieved in terms of clinical
There was considerable heterogeneity in terms of radiographic attachment level and PPD reduction. Moreover, titanium granules
46
bone gain and disease resolution. For instance, Nart et al. used a have been suggested as bone substitutes. Radiographic bone gain
freeze-­dried allograft combined with locally delivered antibiotics was outperformed when compared to control groups (OFD); how-
and found a mean radiographic bone gain of 3.6 mm, while Monaca ever, disease resolution was, in general, low. 21,26 Therefore, the
35
et al. found a bone gain of only 0.4 mm. This difference may be most suitable bone substitute for use in reconstructive therapy
partially due to the follow-­up durations (the latter was reported at remains unclear.
the 5-­year follow-­up, while the former was reported at the 1-­year
follow-­up). Xenografts have been used alone,47,48 in combination
with autogenous bone,49 with 10% collagen, 29,36 and in combi- 8 | S I G N I FI C A N C E O F B I O LO G I C A L
nation with biologics. 33
In noncomparative studies, disease res- AG E NT S
olution ranged from 50%50 to 85% 49 at the 12-­m onth follow-­up.
Aghazadeh et al. 51 compared the use of autogenous bone to a Biologics are a group of agents or mediators that work through various
xenograft. Interestingly, approximately 2x greater disease resolu- mechanisms to promote tissue generation. These molecules promote
tion and radiographic bone gain were found when xenografts were a variety of essential cellular events in wound healing, including DNA
used. One report, 29 however, noted no significant differences in synthesis, chemotaxis, cell differentiation, mitogenesis, and matrix bio-
terms of bone gain or clinical resolution of peri-­implantitis when synthesis. Consequently, these biologics have been utilized to enhance
collagenated xenografts were used compared to OFD. Roccuzzo hard tissue regeneration procedures, enhance healing potential, and
36
et al. using the same bone substitute achieved 45% disease res- promote more rapid wound closure.54,55 The use of biologics in the
olution at the 60-­m onth follow-­up. Synthetic bone substitutes periodontal and implantology arenas has been extensively studied.55,56
52
were further investigated. De Tapia et al. evaluated the effect Nevertheless, the literature on peri-­implantitis therapy is sparse.
of hydroxyapatite/tricalcium phosphate in reconstructive ther- Hamzacebi et al.57 in an RCT compared OFD to OFD combined with
apy. When the surface was decontaminated with titanium brushes platelet-­rich fibrin (PRF) as a reconstructive agent. At the 6-­month fol-
as a mechanical method, the mean disease resolution amounted low-­up, PPD reduction (mean difference approximately 0.4 mm), gain
to 66% with a radiographic bone gain of 2.6 mm. Thus, Schwarz in attachment (mean difference approximately 1.5 mm) and keratinized
et al. 53 compared hydroxyapatite and demineralized bovine bone mucosa gain favored the sites where PRF was used. For example, Isler
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206 MONJE et al.

F I G U R E 9 Moderate intrabony peri-­

implantitis defect (class Ic) managed by
means of mineralized and demineralized
allografts applying a transmucosal healing
approach. Clinical and radiographic images
at the 24-­month follow-­up showed clinical
health and radiographic bone gain.

et al.58 tested the effectiveness of concentrated growth factors (CGFs) 1 mm). Nevertheless, no significant differences were noted in the
in combination with reconstructive therapy with the same interven- evaluated clinical parameters. A long-­term case series study reported
tion and a collagen membrane. At the 36-­month follow-­up, the use of the use of EMD or platelet-­derived growth factors (PDGF) as adjuncts
the collagen membrane outperformed the use of CGF in terms of PPD to reconstructive therapy to manage advanced peri-­implantitis bone
reduction. Hence, the effectiveness of autogenous growth factors is defects. In a mean follow-­up period of 48 months, a mean radiographic
28
controversial. However, Isehed et al. compared EMD to OFD of an- bone gain and clinical bone gain of 3.6 and 6.8 mm were noted, respec-
gular peri-­implant bone defects at the 60-­month follow-­up. It was dem- tively. Therefore, the use of heterologous biologics is promising, but
onstrated that radiographic bone level was superior in sites managed further investigations are warranted to better understand the added
by means of reconstructive therapy (mean difference approximately benefit of these to reconstructive therapy.
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MONJE et al. 207

F I G U R E 1 0 Moderate combined peri-­

implantitis defects (class IIIb) managed by
means of combined therapy. A mixture
of autogenous bone and xenografts was
used as the grafting material. Due to the
partial continence of the bone defect,
a collagen barrier membrane was used.
Note peri-­implant health and radiographic
bone gain at the 24-­month follow-­up.
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208 MONJE et al.

F I G U R E 1 1 Moderate peri-­implantitis
bone defect (class Ib) in the esthetic area.
Surface decontamination was performed
by means of an electrolytic approach.
Reconstructive therapy was carried out
in terms of a mixture of autogenous bone
and xenograft in an equal ratio. A barrier
membrane to enhance the stability of
the graft and a connective tissue graft to
minimize mucosal recession were used
as adjuncts. Peri-­implant health and
radiographic bone gain were noted at the
12-­month follow-­up.

9 | S I G N I FI C A N C E O F TH E BA R R I E R assessing the effect of resorbable (collagen-­based) membranes on

MEMBR ANE bone expression have noted that there is an increase in osteocalcin,
cathepsin K and receptor activator of nuclear kappa-­β factor.62 This
The term “guided bone regeneration” implies the use of barrier mem- type of membrane hosts different cell phenotypes that progressively
branes to fulfil the principle of “compartmentalization” (Figures 7 secrete major bone-­related growth factors such as bone morphoge-
and 8).59 Hence, the barrier membrane aims to promote bone for- netic protein-­2.62 Therefore, the function of the barrier membrane is
mation while acting as a passive barrier to preclude soft tissue in- not merely to exclude undesired cells but also to accelerate de novo
growth. Moreover, the effect of the barrier membrane has further bone formation.
been shown to promote bone formation, as it induces molecular and Hürzeler et al., in a preclinical model, validated the beneficial
cellular events. Preclinical studies have demonstrated that the use use of bone grafting combined with barrier membrane to enhance
of nonresorbable barrier membranes enhances the levels of Runx2-­ radiographic bone level.63 This approach has further been proven
positive osteoprogenitor cells, osteocalcin, alkaline phosphatase, beneficial in case series and cohort studies. 23,46,49,64,65 Therefore,
osteopontin, and sialoprotein.60–­62 In fact, barrier membranes have as noted, reconstructive therapy seems beneficial in general lines.
been shown to promote the expression of tissue by increasing matrix Now, the issue that needs to be addressed is the added benefit
metallopeptidases 2 and 9 along with interleukins 1 and 6.61 Studies of using a barrier membrane to fulfill the principle of guided bone
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MONJE et al. 209

regeneration. In a 60-­month follow-­up study, Ross-­Jansåker et al.66 10 | S I G N I FI C A N C E O F TH E H E A LI N G

noted no remarkable clinical or radiographic differences in sites re- A PPROAC H
constructed by means of an algae-­derived bone grafting material
with (1.3 mm) or without barrier membrane (1.1 mm). In contrast, Limited evidence exists to date using the submerged healing approach
Schwarz et al.67 in a 48-­month study showed an enhancement in for the surgical management of peri-­implantitis. Roos-­Jansaker
clinical and radiographic parameters that favored the use of colla- et al.31 in a case series demonstrated that applying reconstructive
gen membrane when compared to the use of nanocrystalline hy- therapy and submerged healing for 6 months, a reduction of PPD
droxyapatite alone. In agreement, Isler et al. 58 in a 36-­month clinical by 4.2 mm and a mean defect fill of 2.3 mm were achievable. Sig-
trial demonstrated the outperformance of bone grafting combined nificantly less optimal outcomes were obtained in the same group71
with a collagen membrane (1.7 mm) when compared to the use when applying nonsubmerged healing. Monje et al.49 showed that
of anorganic bovine bone grafting combined with concentrated the defect depth and PPD were reduced by 2.2 and 3.7 mm, respec-
growth factors (1.4 mm) in reconstructive therapy. Monje et al.17 tively. Schlee et al.72 in an 18-­month study showed that submerged
indicated that cross-­linked barrier membranes do not exert an influ- healing for 6 months resulted in ~3 mm of radiographic bone gain.
ence on the clinical and radiographic variables. In fact, radiographic Schwarz et al.73 in a preclinical study demonstrated that submerged
bone gain was similar for sites reconstructed by means of allografts healing improved the surgical treatment outcome in terms of radio-
combined with membrane and for sites grafted but where barrier graphic and histomorphometric findings (bone-­to-­implant contact).
membrane was not used (1.7 mm). Regidor et al.68 tested the ad- Again, the primary drawbacks of this technique are that to promote
junctive effect of a collagen membrane to an anorganic bovine bone submerged healing, the prosthesis must be removed in advance of
with 10% collagen in a 12-­month follow-­up trial. Radiographic bone surgical therapy, and placement should not be performed <4 months
gain and PPD reduction amounted to 1.2 and 4.4 mm, respectively. after surgery. Moreover, primary intention healing may lead to a dis-
No significant differences in disease resolution were achieved. It is tortion of the mucosal margin and a reduction in the keratinized mu-
interesting to note, however, that postoperative complications such cosa. Hence, even though it may offer some benefits, transmucosal
as soft tissue dehiscence and exposure of the particulate bone graft (nonsubmerged) healing seems to be more practical for the patient
and/or membrane were recorded for the test sites. Longer surgical and the operator.
times (approximately10 min) and higher levels of self-­reported pain
at 2 weeks were further observed in the test group. It is worth not-
ing that there are variables that might be key in understanding the 11 | CO N C LU D I N G R E M A R K S
above-­listed findings. For instance, there was high heterogeneity in
the defect configurations, type of bone grafting materials, and im- Reconstructive therapy is effective to gain radiographic bone
plant position. Featuring bone morphology is relevant considering level and to establish a healthy peri-­implant condition. Therefore,
that the number of residual walls along with implant position in the in scenarios exhibiting contained/angular defects, the applica-
bucco-­lingual perspective dictate continence. 8,69 Moreover, the na- tion of bone grafting materials may assist in arresting the disorder
ture of bone grafting materials may further influence the stability while increasing the support and minimizing mucosal recession.
achievable by the graft itself within the bone defect. While partic- However, the most effective bone substitute for reconstructive
ulated materials are less prone to stabilization, other presentations, therapy is unclear. The application of barrier membranes, never-
such as fibers or collagenated materials, might promote space main- theless, does not seem to enhance the outcome of well-­contained
tenance in a more effective manner. Hence, although comparative defects. Nonetheless, their use in partially contained defects re-
studies do not suggest the adjunct use of barrier membranes; it mains debatable. Furthermore, the use of biologics is promising,
may rely upon the stability achievable by the bone grafting material even though there is limited evidence regarding their effective-
(Table 5 Figures 9–­11). ness in peri-­implantitis therapy.
Concerning the nature of the membrane, most of the studies
assessing reconstructive measures reported the use of resorbable AC K N OW L E D G M E N T S
membranes.8,22,24,31,49 Other authors, instead, included in their sur- The authors thank Dr. Ryan Noh (University of Toronto, Toronto,
gical protocol the use of nonresorbable membranes. Wen et al.70 in Canada) for the illustrations. The illustrations were sponsored by the
a prospective cohort study applied reconstructive therapy by means Department of Periodontology, Universitat Internacional de Catalu-
of a composite bone graft and a nonresorbable membrane (dPTFE) nya, Barcelona, Spain.)
in a submerged healing approach. At 8 months, the clinical bone gain
reported at re-­entry was ~3.5 mm. Nevertheless, the main shortcom- C O N FL I C T O F I N T E R E S T S TAT E M E N T
ings derived from this approach are the high risk of exposure of the The authors have no direct conflicts of interest to declare.
nonresorbable membrane and associated postoperative complica-
tions (i.e., infection) or the disturbance of the mucosal margin (i.e., DATA AVA I L A B I L I T Y S TAT E M E N T
reduction of the vestibular depth and the buccal band of keratinized Data sharing is not applicable to this article as no new data were cre-
mucosa). ated or analyzed in this study.
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210 MONJE et al.

ORCID 19. Tonetti MS, Pini-­Prato G, Cortellini P. Periodontal regeneration of

Alberto Monje https://orcid.org/0000-0001-8292-1927 human intrabony defects. IV. Determinants of healing response. J
Periodontol. 1993;64:934-­940.
20. Monje A, Schwarz F. Principles of combined surgical therapy
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