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Year: 2009

A systematic review assessing soft tissue augmentationtechniques

Thoma, D S; Benić, G I; Zwahlen, M; Hämmerle, C H F; Jung, R E

Thoma, D S; Benić, G I; Zwahlen, M; Hämmerle, C H F; Jung, R E (2009). A systematic review assessing softtissue augmentation techniques. Clinical Oral Implants Research, 20(Suppl. 4):146-165.Postprint available at:http://www.zora.uzh.ch

Posted at the Zurich Open Repository and Archive, University of Zurich.http://www.zora.uzh.ch

Originally published at:Clinical Oral Implants Research 2009, 20(Suppl. 4):146-165.

Thoma, D S; Benić, G I; Zwahlen, M; Hämmerle, C H F; Jung, R E (2009). A systematic review assessing softtissue augmentation techniques. Clinical Oral Implants Research, 20(Suppl. 4):146-165.Postprint available at:http://www.zora.uzh.ch

Posted at the Zurich Open Repository and Archive, University of Zurich.http://www.zora.uzh.ch

Originally published at:Clinical Oral Implants Research 2009, 20(Suppl. 4):146-165.

A systematic review assessing soft tissue augmentationtechniques

Abstract

Aim: The aim of the present review was to systematically assess the dental literature in terms of softtissue grafting techniques. The focused question was: is there superiority of one method over others foraugmentation and stability of the augmented soft tissue in terms of increasing the width of keratinizedtissue (part 1), and gain in soft tissue volume (part 2). Methods: A Medline search was performed forhuman studies focusing on augmentation of keratinized tissue and/or soft tissue volume, andcomplimented by additional hand searching. Relevant studies were identified and statistical resultsreported for meta-analyses including the test minus control weighted mean differences (WMD) with95% confidence intervals (CI), the I-squared statistic for tests of heterogeneity, and the number ofsignificant studies. Results: Twenty-five (part 1) and three (part 2) studies met the inclusion criteria; 14studies (part 1) were eligible for comparison using meta-analyses. An apically positionedflap/vestibuloplasty (APF/V) procedure resulted in a statistically significantly greater gain in keratinizedtissue than untreated controls. APF/V plus autogenous tissue revealed statistically significant moreattached gingiva compared to untreated controls and a borderline statistical significance compared toAPF/V plus allogenic tissue. Statistically significantly more shrinkage was observed for APF/V plusallogenic graft compared to APF/V plus autogenous tissue. Patient-centered outcomes did not reveal asuperiority of any of the treatment methods regarding post-operative complications. The 3 studiesreporting on soft tissue volume augmentation could not be compared due to lack of homogeneity. Theuse of subepithelial connective tissue grafts (SCTGs) resulted in statistically significantly more softtissue volume gain compared to free gingival grafts (FGGs). Conclusions: APF/V is a successfultreatment concept to increase the width of keratinized tissue or attached gingiva around teeth. Theaddition of autogenous tissue statistically significantly increases the width of attached gingiva. For softtissue volume augmentation only limited data are available favoring SCTGs over FGG.

A systematic review assessing soft tissue augmentation techniques – EAO Group 3 Thoma DS,1 Benić GI,1 Zwahlen M,2 Hämmerle CHF,1 Jung RE1

Key words:

soft tissue augmentation, keratinized tissue, soft tissue volume, subepithelial connective tissue graft, free gingival graft, allogenic dermal matrix, human fibroblast-derived dermal substitute, vestibuloplasty

Running title:

Soft tissue grafting – a systematic review

Address for correspondence: Daniel S. Thoma, Dr. med. dent.

Clinic for Fixed and Removable Prosthodontics and Dental Material Science University of Zurich Plattenstrasse 11 CH-8032 Zurich, Switzerland Phone: +41 44 634 32 57 Fax: +41 44 634 43 05 e-mail: [email protected]

1 Clinic for Fixed and Removable Prosthodontics and Dental Material Science, University of

Zurich, Zurich, Switzerland 2 Institute of Social and Preventive Medicine, University of Berne, Berne, Switzerland

Abstract Aim: The aim of the present review was to systematically assess the dental literature in terms

of soft tissue grafting techniques. The focused question was: is there superiority of one

method over others for augmentation and stability of the augmented soft tissue in terms of

increasing the width of keratinized tissue (part 1), and gain in soft tissue volume (part 2).

Methods: A Medline search was performed for human studies focusing on augmentation of

keratinized tissue and/or soft tissue volume, and complimented by additional hand searching.

Relevant studies were identified and statistical results reported for meta-analyses including

the test minus control weighted mean differences (WMD) with 95% confidence intervals (CI),

the I-squared statistic for tests of heterogeneity, and the number of significant studies.

Results: Twenty-five (part 1) and three (part 2) studies met the inclusion criteria; 14 studies

(part 1) were eligible for comparison using meta-analyses. An apically positioned

flap/vestibuloplasty (APF/V) procedure resulted in a statistically significantly greater gain in

keratinized tissue than untreated controls. APF/V plus autogenous tissue revealed statistically

significant more attached gingiva compared to untreated controls and a borderline statistical

significance compared to APF/V plus allogenic tissue. Statistically significantly more

shrinkage was observed for APF/V plus allogenic graft compared to APF/V plus autogenous

tissue. Patient-centered outcomes did not reveal a superiority of any of the treatment methods

regarding post-operative complications. The 3 studies reporting on soft tissue volume

augmentation could not be compared due to lack of homogeneity. The use of subepithelial

connective tissue grafts (SCTGs) resulted in statistically significantly more soft tissue volume

gain compared to free gingival grafts (FGGs).

Conclusions: APF/V is a successful treatment concept to increase the width of keratinized

tissue or attached gingiva around teeth. The addition of autogenous tissue statistically

significantly increases the width of attached gingiva. For soft tissue volume augmentation

only limited data are available favoring SCTGs over FGG.

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Introduction

Soft tissue augmentation with autogenous grafts is a widely used procedure in a

variety of disciplines in dentistry. It is indicated in partially and fully edentulous patients to

augment areas with a lack of or a reduced width of keratinized tissue, as well as to increase

soft tissue volume. Various studies suggested associations between an adequate width of

keratinized tissue, higher survival rates of dental implants, health of the peri-implant mucosa,

and an improved esthetic outcome (Adell et al. 1986; Artzi et al. 1993; Langer 1996).

However, two recent reviews concluded that there is insufficient or even a lack of evidence

regarding the influence of the width of keratinized tissue on the survival rate and future

mucosal recessions (Esposito et al. 2007; Cairo et al. 2008).

With respect to teeth, a certain amount of keratinized tissue has been considered

necessary for maintaining periodontal health and prevent gingival recession (Nabers 1966;

Sullivan & Atkins 1969). It was also concluded that for the maintenance of gingival health

2mm of keratinized gingiva is adequate (Lang and Löe 1972). Since an adequate amount of

keratinized tissue has not been defined yet, the decision to augment the width of keratinized

gingiva around dental implants and teeth still depends on the clinician's choice and the

planned surgical and prosthetic treatment. Historically, the methods to augment keratinized

tissue included: i) an apically positioned flap (APF), ii) an APF in combination with

autogenous tissue and, iii) an APF in combination with allogenic tissue (Friedman 1962; Edel

1974; Yukna & Sullivan 1978).

Autogenous soft tissue grafting procedures have also been proposed to surgically

correct localized alveolar defects, as pre-prosthetic site-development, and as ridge

preservation procedures (Seibert 1983; Studer et al. 2000; Jung et al. 2004; Prato et al. 2004).

As for the augmentation of keratinized tissue, traditionally, the free gingival graft (FGG) and

the subepithelial connective tissue graft (SCTG) have been described to increase soft tissue

volume (Seibert 1983).

Disadvantages of using autogenous tissue are mainly due to the harvesting procedure,

which leads to a prolonged healing time at the donor site and therefore to an increased

patient's morbidity (Farnoush 1978; Griffin et al. 2006). Patients often complain about pain

and numbness for several weeks after the surgery (Del Pizzo et al. 2002; Soileau & Brannon

2006). On the other hand, anatomical and individual limitations exist. Depending on the shape

of the palatal vault, the patient's sex and age the quantity and quality of tissue that can be

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retrieved varies. The location of the palatal vessels and nerves further limit the total amount

that is available for grafting procedures (Soileau & Brannon 2006).

In order to overcome these issues with autogenous tissue, alternatives techniques and

materials primarily of allogenic origin have been developed. Among the first products

introduced in mucogingival surgery were freeze-dried skin allografts, initially used as

replacement for FGGs in combination with an APF for the augmentation of keratinized tissue

(Yukna & Sullivan 1978). Later in the eighties, allogenic dermal substitutes like the acellular

dermal matrix graft (ADMG; Alloderm™, Life Cell Corporation, The Woodlands, TX),

originally developed for covering full thickness burn wounds (Wainwright 1995) have been

used to increase keratinized tissue, for root coverage procedure, to deepen the vestibular

fornix, and to augment localized alveolar defects (Wei et al. 2000; Aichelmann-Reidy et al.

2001; Batista et al. 2001; Harris 2003).

Recent techniques follow the guidelines of tissue-engineering. Tissue-engineered

products are based on isolated cells or cell substitutes, tissue-inducing substances (biologic

mediators), and scaffolds of natural or synthetic origin (Langer & Vacanti 1993). In contrast

to ADMG, newer grafts like the human fibroblast-derived dermal substitute (HF-DDS,

Dermagraft⎢, Advanced Tissue Sciences, Inc., La Jolla, CA, USA), and a human skin

equivalent (BCT, Apligraf⎢, Organogenesis, Canton, MA, USA) include a cellular

component. Both grafts have been investigated in clinical trials in comparison to autogenous

soft tissue to increase the width of keratinized tissue (McGuire & Nunn 2005; McGuire et al.

2008).

Since techniques and materials have changed quite extensively over the last decades,

there is a lack of information and a strong need to critically assess the dental literature for

optimized procedures and grafts in terms of soft tissue augmentation.

The aim of the present review was to systematically assess the dental literature in

terms of soft tissue grafting techniques. The focused question was, whether there is

superiority of one method over others for augmentation and stability of the augmented soft

tissue in terms of i) increasing the width of keratinized tissue (part 1), and ii) gain in soft

tissue volume (part 2).

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Material and Methods

Search strategy A Medline (PubMed) search was performed for human studies, including articles

published from January 1, 1966 up to August 31, 2008 in the Dental literature. The search

was limited to the English, French, German, and Italian language. The search was

complemented by manual searches of the reference list of all selected full-text articles.

Additionally, full text articles of reviews published between January 2005 and August 2008

were obtained. An additional hand search was performed searching for relevant studies by

screening these reviews.

Search Terms The following search terms were selected: “acellular dermal matrix” OR “dermal

matrix allograft” OR “alloderm” OR “keratinized gingiva” OR “keratinized tissue” OR “soft

tissue graft” OR “subepithelial connective tissue graft” OR „connective tissue“ OR “free

gingival graft” OR “human fibroblast-derived dermal substitute” OR “dermagraft” OR

“apligraf” OR “gingival autograft” OR “attached gingiva” OR “attached mucosa” OR

“keratinized mucosa” OR “soft tissue augmentation” OR “soft tissue transplantation” OR

„vestibuloplasty“ OR “ridge augmentation” OR “soft tissue correction”. The search was

limited to “human trial“ (MeSH term, clinical studies), and “Dental Journals”. Additionally,

the MeSH terms “clinical trial“, “comparative study“, “controlled clinical trial“, “randomized

controlled trial“, “meta-analysis”, and “review” were used.

Inclusion criteria

The applied inclusion criteria were different for studies dealing with gain of

keratinized tissue or gain of soft tissue volume.

Part 1: augmentation of keratinized tissue Any prospective cohort study with at least 5 patients was included. A follow-up

period of at least 3 months was required. The reported treatment outcomes had to include

either clinical and/or histological measures of the width of keratinized tissue (test) and the

control(s). The primary outcome of the studies had to be localized augmentation of

keratinized tissue.

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Part 2: augmentation of soft tissue volume For studies focusing on soft tissue volume gain, any prospective case series with at

least 5 patients was included. The minimal follow-up time was 3 months. The reported

treatment outcomes had to include either clinical and/or histological measures of the soft

tissue volume.

Exclusion criteria Studies not meeting all inclusion criteria were excluded from the review. Publications

dealing with the following topics were also excluded: in vitro studies, preclinical (animal)

studies, studies dealing with the treatment of recession defects, and studies augmenting soft

tissue in fully edentulous patients.

Selection of studies Titles derived from this broad search were independently screened by 2 authors (DT,

GB) based on the inclusion criteria. Disagreements were resolved by discussion. Cohen’s

Kappa-coefficient was used as a measure of agreement between the 2 readers. Following this,

abstracts of all titles agreed on by both authors were obtained, and screened for meeting the

inclusion criteria. If no abstract was available in the database, the abstract of the printed

article was used. The selected articles were then obtained in full text. If title and abstract did

not provide sufficient information regarding the inclusion criteria, the full report was obtained

as well. Again, disagreements were resolved by discussion.

Finally, the selection based on inclusion/exclusion criteria was made for the full text

articles. For this purpose Material and Methods, and Results of these studies were screened.

This step was again carried out independently by 2 readers. Disagreements were resolved by

discussion.

Data extraction Two reviewers independently extracted the data using data extraction tables. Any

disagreements were resolved by discussion aiming for consensus. For abbreviations used

throughout text, tables, and figures please refer to Table 1.

Part 1: keratinized tissue For studies on keratinized tissue augmentation, information on the following

parameters was extracted: author(s), year of publication, study design, total number of

patients, number of patients test group, number of patients control group(s), total number of

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sites, number of sites test group, number of sites control group(s), follow-up period, graft test

group, graft control group(s), type of treatment, width of keratinized tissue, width of attached

gingiva, shrinkage of attached gingiva, augmented area, shrinkage of augmented area, width

of graft, shrinkage of graft, depth of vestibulum, as well as patient-reported outcomes

(postoperative bleeding, swelling, pain, toleration of procedure), and esthetics). Figure 1

represents a schematic drawing of the analyzed parameters.

Part 2: augmentation of soft tissue volume Information on the following parameters was extracted: author(s), year of publication,

study design, total number of patients, number of patients test group, number of patients

control group(s), total number of sites, number of sites test group, number of sites control

group(s), follow-up period, graft test group, graft control group(s), type of defect, gain/change

in volume.

Statistical Analysis Based on the reported treatment modalities and the outcomes measured, a meta-

analysis was performed for 14 studies for part 1 (keratinized tissue) for three types of

continuous outcome measures: (1) mean change in width of keratinized tissue in mm from

baseline to end of study (10 studies), (2) percentage shrinkage of width of keratinized tissue

in mm from baseline to follow-up (2 studies), (3) mean width of attached gingiva at follow-up

(10 studies). The outcome of interest was, for each study, the post intervention mean

difference between test and control group. To be able to perform a meta-analysis on mean

differences, size of the test and control group and standard deviations of measures of interest

needed to be available from the study reports. Forest plots were produced to graphically

depict study specific mean differences and summary estimates obtained from the meta-

analyses. We report 95% confidence intervals (CI), Cochran’s Q statistic and the I-squared

statistic for testing for and quantifying of heterogeneity. The I-squared measure describes the

proportion of total variation in study estimates that is due to heterogeneity (Higgins &

Thompson 2001). Whenever substantial heterogeneity was present, random effects meta-

analysis was performed. Meta-analyses were performed using the user-written “metan”

command for use in Stata (StataCorp LP, College Station, TX).

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Results

Study characteristics The electronic search identified a total of 1471 titles (for details refer to Fig. 2). From

assessing the titles, 1356 were excluded (inter-reader agreement k=0.82 ± 0.02). The resulting

number of abstracts obtained was 115 out of which 67 were excluded (inter-reader agreement

k=0.81 ± 0.05). Sixty-five full text articles were obtained including 7 studies found through

hand searching. Finally, 25 (keratinized tissue), and 3 (soft tissue volume) articles met the

inclusion criteria.

Exclusion of studies The reasons for excluding studies (n=31, Table 2) after the full text was obtained

were: no reported or insufficient clinical, or histological treatment outcomes (e.g. only

descriptive presentation of results; n=13), no control group (n=8), fully edentulous patients

(n=3), an insufficient number of patients (n=1), retrospective study (n=1), insufficient follow-

up data (n=1), description of technique (n=1), root coverage procedure (n=1), retrospective

study (n=1), soft tissue augmentation in combination with implant placement (n=1).

Included studies The 28 studies that met the inclusion criteria are presented in Tables 3 and 4. Table 3

represents data for studies regarding „keratinized tissue“ (part 1; 25 studies). Table 4 refers to

clinical studies dealing with „soft tissue volume“ (part 2; 3 studies).

Part 1: Keratinized tissue

Treatment outcomes

Patient-based treatment outcomes on augmentation of keratinized tissue retrieved

from 25 included studies are presented in Tables 3, and 5 - 7. Ten studies were designed as

randomized controlled clinical trials (RCT), four as cohort studies, and eleven as controlled

clinical trials (CCT). More than 585 patients were treated for augmentation of keratinized soft

tissue or attached gingiva. The methods and techniques used for augmentation of keratinized

tissue included: no treatment or scaling and root planning, vestibuloplasty, APF in various

forms and designs, APF/V in combination with autogenous tissue (FGG, SCTG), APF/V in

combination with allogenic grafts (ADMG, BCT, FDS, HF-DDS). The mean follow-up

period was 63 weeks (12 to 432). The reason for treating the patients encompassed a lack of

or an inadequate width of attached gingiva/keratinized tissue (22 studies), or vestibuloplasty

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(3 studies). In summary, 14 studies were eligible for comparison using meta-analyses i) ten

studies in terms of mean gain in width of keratinized tissue, ii) two studies in terms of

shrinkage of keratinized tissue and, iii) ten studies in terms of final width of attached gingiva.

(1) Mean gain in width of keratinized tissue (Table 5; Fig. 3)

A total of 12 studies (7 RCTs, 3 CCTs, 2 cohort studies) could be compared for mean

gain in keratinized tissue using meta-analyses (Table 5). The use of an APF/V plus

autogenous tissue resulted in a statistically significant weighted mean difference (WMD) of

4.49mm (4.28, 4.71) compared to no treatment (p = 0.000) (Fig. 3A). The I-square value of

96.6% indicated a statistically significant heterogeneity between the 4 studies (p = 0.000).

Based on one study reporting on outcomes of two different APF/V plus SCTG techniques,

there was a statistically not significant WMD of 0.34mm (-0.45, 1.13) favoring method 11

over method 22 (p = 0.401; Fig. 3B). The use of an APF/V plus an allogenic graft (ADMG)

was slightly more favorable in terms of gain in keratinized tissue than an APF/V alone

(0.70mm; -0.14, 1.54) (Fig. 3C). A borderline statistical difference was observed between the

two treatment modalities (p = 0.052). The mean difference between an APF/V with either an

allogenic graft or an autogenous graft was -0.85mm (-1.71, 0.01) (Fig. 3D). Even though

showing a high standard deviation, this mean gain in keratinized tissue was statistically

significantly different in favor of the groups using autogenous tissue (p = 0.000). The I-

squared value indicated significant heterogeneity between the different studies (94.6%; p =

0.000). Fenestration of the flap when using a FDS statistically significantly improved the gain

in keratinized tissue (1.22mm; 0.71, 1.73; p = 0.000) (Fig. 3E).

(2) Percent shrinkage of keratinized tissue (Table 6; Fig. 4)

Two RCTs reporting on percent shrinkage of keratinized tissue were compared using

a meta-analysis (Wei et al. 2000; McGuire & Nunn 2005; Table 6; Fig. 4). The WMD with

95% confidence interval (CI) between the allogenic groups (APF/V plus ADMG or HF-DDS)

and the control groups (APF/V plus FGG) was 28.41% (23.56, 33.26). The mean shrinkage

was statistically significantly greater in the allogenic groups (p = 0.0000). The I-squared

value of 95.1% indicated a significant heterogeneity between the two studies (p = 0.000).

1 A partial thickness flap is raised and the SCTG is taken from below the palatal surface. 2 The SCTG is obtained by the thinning of a full thickness palatal flap.

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(3) Width of attached gingiva (Table 7; Fig. 5)

Fifteen studies reported data on the width of the attached gingiva including 6 RCTs, 8

CCTs, and 1 cohort study (Table 7). Based on 5 studies, the width of the attached gingiva

postoperatively was statistically significantly greater when APF/V plus autogenous tissue

groups were compared to control groups (no treatment) (p = 0.000) (Fig. 5A). The WMD

with 95% confidence interval (CI) was 3.94mm (3.64, 4.23). The I-squared value of 98.4%

indicated a significant heterogeneity between the studies (p = 0.000). The comparison

between APF/V with or without the addition of autogenous tissue revealed a statistically

significant WMD of 0.83mm (0.42, 1.25) in favor of the groups using autogenous tissue (p =

0.010) (Fig. 5B). Again, the I-squared value of 78.4% revealed significant heterogeneity

between the two studies (p = 0.010). The addition of an allogenic graft (ADMG) to an APF/V

resulted in a minor gain of 0.70mm (-0.10, 1.50) compared to the APF/V alone (Fig. 5C). The

comparison between an APF/V with either an FGG or a BCT revealed a statistically

significant difference of 1.52mm (1.73, 1.31) in favor of the group using the autogenous FGG

(p = 0.000) (Fig. 5D). One study comparing an APF/V plus FDS with or without fenestration

of the flap demonstrated a statistically significant WMD of 1.17mm (0.61, 1.73) in favor of

the group using a fenestration of the flap (p = 0.000; Fig. 5E).

(4) Percent shrinkage of attached gingiva

One CCT reported on the shrinkage of the attached gingiva using two different

treatment modalities (Schoo & Coppes 1976). The shrinkage of the attached gingiva was

statistically significantly greater for an APF/V in combination with lyophilized dura mater

(mean = 63.1%; SD = 9.3) compared to an APF/V with a FGG (20.7%; SD 11.1) (Schoo &

Coppes 1976).

(5) Percent shrinkage of graft / grafted area

Seven CCTs, 1 RCT, and 1 cohort study reported on the shrinkage of the graft /

grafted area (Richter et al. 1973; Matthiessen & Diedrich 1974; James & McFall 1978; Lange

et al. 1981; Mörmann et al. 1981; Marxer et al. 1982; Pöllmann & Scherer 1983). No

statistically significant differences were observed between most of the various treatment

modalities (different techniques for vestibuloplasty). A borderline significance was observed

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in favor of a FGG placed on the periosteum (36.67%) instead of directly on the bone

(23.25%) (James & McFall 1978). In one study, FGGs were placed at sites with less than

1mm of attached gingiva (Mörmann et al. 1981). The FGGs were retrieved either by using a

mucotom or a blade and, with various thicknesses ranging from 0.37mm to 0.92mm. The

group with the thickest mean FGG retrieved showed statistically significantly less shrinkage

(30%) than grafts with a mean thickness of 0.37mm (45% shrinkage) and 0.56mm (44%).

(6) Vestibular area

One CCT evaluated the augmented vestibular area for two different treatment

modalities (Lange et al. 1981). A greater vestibular area was observed after 6 months for the

control group (vestibuloplasty according to Plagmann 1979; 297mm2) compared to the test

group (vestibuloplasty according to Schmid & Mörmann 1976; 236mm2) (Lange et al. 1981).

(7) Depth of vestibulum

Two CCTs reported data for the depth of the vestibulum following different

vestibuloplasty procedures (Lange et al. 1981; Marxer et al. 1982). No statistically significant

differences were observed between an APF in combination with a FGG (mean 3.9mm; SD

1.1) compared to an Edlan-Mejchar flap (3.9mm; SD 1.1) for the treatment of an inadequate

width of attached gingiva (Marxer et al. 1982). Slightly more gain in vestibular depth was

found using the Schmid & Mörmann 1976 procedure (12.5%) than with the Plagmann 1979

procedure (12.2%) (Lange et al. 1981).

(8) Patient-reported outcomes and esthetics

Two studies (1 CCT, 1 RCT) reported on post-operative pain (Dordick et al. 1976;

Harris 2001). In one study, patients were treated for an inadequate width of gingiva.

Perception of pain was measured based on the utilization of analgesic postoperatively.

Patients felt slightly more comfortable when the FGG was placed on the periosteum instead

of placing it directly on bone. The differences between the groups were not statistically

significantly different (Dordick et al. 1976). In the second study, three treatment modalities

were compared for augmentation of keratinized tissue: i) an ADMG, ii) a SCTG, iii) an FGG.

No differences in pain perception were observed between patients treated with ADMG and

FGG; however, more pain was reported for SCTG- compared to ADMG-treated patients

(Harris 2001).

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No significant differences were observed with respect to postoperative bleeding in a

RCT comparing a tissue-engineered skin product (BCT) to a FGG (McGuire et al. 2008).

However, it appears to be a difference whether a FGG is placed directly on bone (less

bleeding, less swelling) or on periosteum for post-operative hemostasis and swelling (Dordick

et al. 1976).

The overall patient morbidity (pain, swelling, bleeding) was evaluated in another

RCT revealing no differences between the two treatment modalities (HF-DDS vs. FGG;

McGuire & Nunn 2005). However, subject's treatment preference was significantly greater in

the allograft group (BCT) compared to the control group (FGG) in a recently published study

(McGuire et al. 2008). In addition, a better color and texture match to the surrounding tissue

was reported for the allograft groups (HF-DDS; BCT) compared to control sites (FGG) in two

recent studies (McGuire & Nunn 2005; McGuire et al. 2008).

Part 2: Augmentation of soft tissue volume

Three studies met the inclusion criteria as they reported on soft tissue volume

augmentation (Allen et al. 1985; Studer et al. 2000; Batista et al. 2001). Two studies were

designed as cohort studies (Allen et al. 1985; Studer et al. 2000), one as a case series (Batista

et al. 2001). No meta-analysis could be performed due to heterogeneity in study design and

treatment modalities.

Treatment outcomes (Table 8)

In the first case series, 21 patients with 26 localized alveolar defects were treated

either with a SCTG or hydroxylapatite implants. The authors reported that 14 of 14 sites

(SCTG) showed some shrinkage within the first 4-6 weeks, but that the augmented sites

remained stable for three years. In 10 of 12 sites treated with hydroxylapatite implants, no

shrinkage was observed. It was not mentioned how the measurements were performed (Allen

et al. 1985). In the second case series, localized alveolar defects in eight patients with 18 sites

were treated with ADMG. A gain in vertical ridge width of 0.61mm (SD 0.77) and in

horizontal ridge width of 1.72mm (SD 0.59) was observed over 6 months. The shrinkage of

the horizontal ridge width was 41.4% over the same period (Batista et al. 2001). In a cohort

study, localized alveolar ridge defects were treated with either a FGG or a SCTG. Patients

were followed for 3.5 months. The augmented sites revealed a volume gain between 159

mm3 (SCTG; SD = 80) and 104 mm3 (FGG; SD = 31). The differences between the two

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treatment modalities were statistically significant in favor of the SCTG group. The untreated

defects showed a slight increase in volume of 6mm3 (SD = 5.4), which was statistically

significantly different compared to the two test groups using autogenous tissue (Studer et al.

2000).

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Discussion

The present systematic review focused to answer the question whether there is superiority of

one method to others for soft tissue augmentation techniques. In terms of increasing the width

of keratinized tissue, 25 studies met the inclusion criteria. Out of these, 14 could be compared

using meta-analyses. In terms of soft tissue volume augmentation, only 3 studies met the

inclusion criteria. No meta-analysis could be performed due to heterogeneity between the

studies.

Part 1 (augmentation of keratinized tissue/attached gingiva)

Mean gain in width of keratinized tissue

The present review demonstrated superiority of APF/V plus autogenous tissue. This

information is derived from studies comparing APF/V plus autogenous tissue versus scaling

and root planing and versus untreated controls. The overall WMD was statistically significant,

even though showing large heterogeneity between the studies.

It would be interesting to see what the effect of autogenous tissue in this treatment concept is.

However, this outcome could not be evaluated due to a lack of further control groups or other

studies. There is a need for studies evaluating the effect of autogenous tissue, especially since

this treatment concept is associated with higher morbidity due to the second surgical site

(Wessel & Tatakis 2008).

To overcome issues associated with higher morbidity when autogenous tissue is used,

allogenic grafts have been introduced in mucogingival surgery. Allogenic grafts have been

tested in combination with APF/V. The results of one included study demonstrated only a

borderline statistical significance compared to APF/V alone (Mohammadi et al. 2007).

Based on the results of this review, the direct comparison of APF/V plus either autogenous or

allogenic tissue revealed a statistically significant difference favoring the use of autogenous

tissue. Interestingly, differences between the various allogenic grafts were observed. One

study compared an APF/V procedure with the addition of an ADMG, a FGG, or a SCTG

(Harris 2001). The ADMG was more favorable as the FGG, but slightly less effective

compared to the SCTG. On the other hand, the tissue-engineered grafts (HF-DDS, BCT)

demonstrated statistically significantly less gain in keratinized tissue than the respective

control groups (autogenous tissue). Overall, an APF/V plus an ADMG appears to be more

effective than the tissue-engineered grafts (BCT, HF-DDS) in comparison with autogenous

tissue. However, one might speculate that these observations are due to the fact that the

initially transplanted width of the graft was larger in one study (Harris 2001) than in the other

14

two studies, where the width of the grafts for control and test sites was held constant (5mm)

(McGuire & Nunn 2005; McGuire et al. 2008). Unfortunately, the first study does not provide

information on the width of the graft that was transplanted (Harris 2001).

Percent shrinkage of keratinized tissue

The meta-analysis revealed statistically significant less shrinkage for the autogenous control

groups (FGG; Table 5; Fig. 3). The reason for the large shrinkage of ADMG compared to

autogenous tissue may be due to its fabrication process. ADMG is processed from cadaver

skin and the epidermis and cellular material are removed. Histologic observations of ADMG

placed to increase the width of keratinized tissue showed tissue that substantially differed

from any oral mucosa (Wei et al. 2002). The connective tissue portion of the ADMG

contained dense collagen fibers with scattered elastic fibers. The epithelial layer covering the

connective tissue showed heterogenous expression of keratinization and a flat epithelium-

connective tissue interface. The epithelium was mostly para- or orthokeratinized towards the

gingiva and non-keratinized to the alveolar mucosa. The authors suggested that due to the

non-vital matrix of the ADMG the epithelium-connective tissue of the surrounding recipient

site directed the epithelium differentiation of the ADMG (Wei et al. 2002). These findings

may predominantly explain the high shrinkage of this allogenic dermal matrix. On the other

hand, the HF-DDS is obtained from neonatal fibroblasts on a polyglyactin mesh. The included

cells can multiply and produce collagen and growth factors, which can produce greater tissue.

The shrinkage reported for HF-DDS is still greater than for autogenous tissue, but the mean

shrinkage values are lower in comparison to studies using ADMG (Wei et al. 2000; McGuire

& Nunn 2005). The inclusion of living cells (tissue-engineering) may therefore play a critical

role as the cells could enhance the results by stabilizing the allogenic tissue through the

production of extracellular matrix molecules, fibers and growth factors.

Shrinkage of the graft / grafted area

No statistically significant differences were observed in the various studies comparing

different vestibuloplasty procedures. The only difference observed was that more shrinkage of

FGGs was observed when they were placed on the periosteum rather than on bone (James &

McFall 1978). This observation from one single study is surprising since the periosteum is

known to be a highly vascularized tissue and can provide blood supply within short distance

to grafts. The outcome is also in contrast to an experimental study in rats, which showed the

importance of the periosteum for the healing of full-thickness skin defects (Koga et al. 2007).

It was demonstrated that the thickness of the grafts (FGG) had an influence on the shrinkage

(Mörmann et al. 1981). The thickest grafts showed statistically significantly the least

15

shrinkage. Similar findings with an allogenic graft (HF-DDS) regarding the relationship

thickness and shrinkage were reported (McGuire & Nunn 2005). In that study, multiple-layer

HF-DDS showed significantly less shrinkage and greater keratinized tissue than monolayer

HF-DDS.

Width of attached gingiva

The results of the present review indicate that the combination of APF/V plus autogenous

tissue is a successful treatment concept with a statistically significantly greater increase in

attached gingiva compared to untreated control groups. The addition of autogenous tissue to

an APF/V improved the outcome compared to an APF/V alone. Unfortunately, no studies

were identified comparing an APF/V to untreated control groups. Therefore, the effect of the

APF/V procedure can only be calculated indirectly. Based on a WMD between APF/V plus

autogenous tissue and an APF/V procedure of 0.83mm (0.42, 1.25), and a WMD between

APF/V plus autogenous tissue and untreated controls of 3.94mm (3.64, 4.23), the effect of the

APF/V should be around 3mm. The greatest increase in width of keratinized tissue therefore

derives from the APF/V procedure. The effect of the autogenous tissue appears to be rather

small, even though statistically significant based on two included studies. When using an

APF/V in combination with a FDS demonstrated that the fenestration of the flap had a

statistically significant influence on the outcome (Gher et al. 1980). The effect of the FDS

remains unclear as the cited study did not have a control group without the allogenic graft and

no other studies using FDS were included. Another study using an APF/V procedure with or

without the addition of an ADMG demonstrated a borderline difference in favor of the group

using the ADMG (Mohammadi et al. 2007). The direct comparison between a tissue-

engineered product (BCT) and a FGG both in combination with an APF/V resulted in

statistically significantly more attached gingiva for the autogenous group (FGG) (McGuire et

al. 2008). Again, no other control group (APF/V alone) was included. The effect of the

APF/V alone could therefore not be calculated.

Patient-reported outcomes and esthetics

A recent publication evaluating patient outcomes following subepithelial connective tissue

graft and free gingival graft procedures demonstrated that FGG is associated with a greater

incidence of donor site pain compared to SCTG at three days (Wessel & Tatakis 2008). In the

present review, five included studies reported outcomes on the toleration of the procedure, or

the postoperative comfort of the patients. Patients felt slightly more comfortable, but reported

more bleeding and swelling when the FGG was placed on the periosteum rather than directly

on the bone (Dordick et al. 1976). The major advantage of using allogenic grafts instead of

16

autogenous tissue is suggested to be the abandonment of a second surgical site. In a

prospective clinical study evaluating postoperative complications following gingival

augmentation procedures, the use of ADMG (instead of FGG or SCTG) significantly reduced

the probability of swelling and bleeding at the donor site (Griffin et al. 2006). The same

treatment modalities (ADMG, FGG, SCTG) were compared in one of the included studies

(Harris 2001). No differences in pain perception were observed between patients treated with

ADMG or FGG; but, more pain was reported by patients receiving SCTGs than ADMGs. No

significant differences were observed with respect to postoperative bleeding in a study

comparing a tissue-engineered graft (BCT) to an FGG, however the patient's treatment

preference was significantly greater in the allogenic group (BCT; McGuire et al. 2008). The

overall patient morbidity (pain, swelling, bleeding) was comparable when the two treatment

modalities HF-DDS and FGG were evaluated (McGuire & Nunn 2005). One reason for these

observations might be the fact that patients were treated in a split-mouth design, which could

make it difficult for the patients to differentiate between the two sites. Another explanation is

that the questionnaires were not administered to the patients until 3 to 12 months following

the surgery. Important information of the postoperative outcome might have been missed.

Part 2 (augmentation of soft tissue volume)

Three studies met the inclusion criteria for augmentation of soft tissue volume. Out of these,

only one was designed as a comparative cohort study (Studer et al. 2000). The greatest

amount of soft tissue volume was observed for the SCTG group with significant differences to

the control groups (FGG, untreated sites). No comparative studies were found using allogenic

grafts instead of autogenous tissue for volumetric augmentation. The evidence for volumetric

soft tissue augmentation techniques is therefore low. SCTGs can be recommended for

augmentation of localized alveolar defects. However, one has to bear in mind that these

results are derived from only one study including 30 patients with a follow-up of 14 weeks

and a significant decrease in volume (graft shrinkage) between 4 and 14 weeks.

Several reasons may be responsible for the low number of studies published in this field: first,

the currently investigated grafts other than autogenous tissue are very thin due to the

manufacturing process. Any volume augmentation would likely require larger amounts of

tissue or, a folding procedure would be necessary to gain greater volume. A folding process

further hampers vascularization of the graft and could provoke extensive shrinkage, which is

critical especially for acellular dermal grafts (Batista et al. 2001; Wei et al. 2002). Second,

allogenic grafts including living cells might be a better alternative, since these grafts tend to

show less shrinkage than acellular dermal substitutes. On the other hand, these grafts appear

17

to build an epithelial layer and the effect of a folding procedure remains unclear. Options for

future grafts might include collagen-based matrices, which have been evaluated in preclinical

and clinical studies in ridge preservation techniques and are currently under investigation for

soft tissue volume augmentation (Jung et al. 2004; Heberer et al. 2008; Araujo et al. 2009). In

contrast to grafts to increase the width of keratinized tissue, collagen-based matrices intended

to be used for volume augmentation are not placed in sites with a lack of or a reduced

vascular supply. The grafts are fully surrounded by soft tissue at the recipient site. Therefore,

one might speculate that suitable grafts would not be dependent on enclosed living cells

(tissue-engineered products). On the other hand, higher demands are needed regarding the

mechanical properties since shear and compression forces are constantly applied to the grafts.

Third, and possibly the most important reason is that there is currently no standardized

reliable technique available for the measurement of soft tissue volume. In one of the included

studies, a time-consuming procedure based upon cast measurements was applied. For the

measurements using the so-called Moiré method extensive appliances are required (Studer et

al. 2000). These aspects influence and limit the clinical applicability. In another study,

measurements were performed using a periodontal probe. These measurements may not

reflect the changes of the entire augmented volume (Batista et al. 2001). Recently, a new

method has been described to measure soft tissue volume (Windisch et al. 2007). In operative

dentistry for example an optical system is available that allows one to capture information

about the shape of tooth preparations and the adjacent soft tissue contours (Mörmann &

Brandestini 1996). With this system a three-dimensional image is obtained after scanning the

intraoral anatomy with a camera (Schneider 2003). In a methodological in vitro study, several

datasets of three-dimensional objects were captured and volumetric differences measured.

The tested optical three-dimensional system showed excellent accuracy and high

reproducibility for measuring volume differences between specimens imitating alveolar ridge

defects after augmentation procedures (Windisch et al. 2007). The same method has been

used to measure dimensional changes of the ridge contour in a preclinical study (Fickl et al.

2009) and, to document volumetric soft tissue changes of the interdental papilla (Strebel et al.

2009). Since this method is non-invasive, and has been established in preclinical and clinical

studies, it might be applicable for the desired measurements of soft tissue volume differences.

18

Conclusions

The present systematic review revealed that with respect to increasing the width of

keratinized tissue or attached gingiva around teeth, apically positioned flap/vestibuloplasty

procedures (APF/V) are successful treatment concepts. The addition of autogenous tissue

statistically significantly increases the width of attached gingiva. Based on the included

studies, the various allogenic grafts in combination with APF/V do not improve the outcome

regarding the mean gain in width of keratinized tissue and the width of attached gingiva

postoperatively compared to the use of APF/V plus autogenous tissue. Indeed, allogenic grafts

(BCT, HF-DDS) resultet in better color and texture match to surrounding tissue compared to

free gingival grafts harvested from the palate. For soft tissue volume augmentation only

limited data are available. For localized alveolar defects subepithelial connective tissue grafts

(SCTGs) provided greater volume gain than full-thickness gingival grafts. However, the

evidence is rather weak, since only one comparative cohort study has been published.

Research is needed to investigate current techniques and substitutes in randomized controlled

clinical trials including patient-reported outcome measures and esthetics. Future studies

should be conducted to provide long-term data of at least 12 months of observation period.

Non-invasive standardized methods to characterize the tissue type and to measure gain, loss,

and changes of grafted areas concerning extension, volume and esthetics have to be

established and validated. Future research in soft tissue regeneration should be directed

towards reduction of morbidity, increased reliability and, elimination of autogenous tissue.

Tissue-engineering might be a possibility to improve current techniques and offer new options

in this field.

19

Conflict of interest and source of funding statement

This review has been funded by the Clinic for Fixed and Removable Prosthodontics and

Dental Material Science, University of Zurich. No conflict of interest is reported for this

article.

20

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dermal matrix allografts to achieve increased attached gingiva. Part 1. A clinical study.


Wei, P.C., Laurell, L., Lingen, M.W. & Geivelis, M. (2002) Acellular dermal matrix

allografts to achieve increased attached gingiva. Part 2. A histological comparative study.


27

28

Wessel, J.R. & Tatakis, D.N. (2008) Patient outcomes following subepithelial connective

tissue graft and free gingival graft procedures. Journal of Periodontology 79: 425-430.

Windisch, S.I., Jung, R.E., Sailer, I., Studer, S.P., Ender, A. & Hammerle, C.H. (2007) A new

optical method to evaluate three-dimensional volume changes of alveolar contours: A

methodological in vitro study. Clinical Oral Implants Research 18: 545-551.

Yukna, R.A. & Sullivan, W.M. (1978) Evaluation of resultant tissue type following the

intraoral transplantation of various lyophilized soft tissues. Journal of Periodontal Research

13: 177-184.

Yukna, R.A., Tow, H.D., Caroll, P.B., Vernino, A.R. & Bright, R.W. (1977) Comparative

clinical evaluation of freeze-dried skin allografts and autogenous gingival grafts in humans.

Journal of Clinical Periodontology 4: 191-199.

Figure 1. Schematic drawing of analyzed parameters at dento-gingival unit.

Zur Anzeige wird der QuickTime™ Dekompressor „“

benötigt.keratinized tissue

free gingiva / periodontal probing depth

attached gingiva

margo gingivae

muco-gingival junction

cemento-enamel junction

first electronic search: 1471 titles

Figure 2. Search strategy.

independently selected by 2 reviewers and agreed by both: 115 titles

abstracts obtained

independently selected by 2 reviewers and agreed by both: 58 abstracts

full text obtained

keratinized tissue: 48

final number of studies included keratinized tissue: 25

further handsearching 7 articles (references of full text articles)

inter-reader agreement k = 0.82 ± 0.02

review: 6

excluded: 30

inter-reader agreement k = 0.81 ± 0.05

soft tissue volume: 4

excluded: 1

final number of studies included soft tissue volume: 3

Figure 3 A to E. Meta-analyses of mean gain in width of keratinized tissue. Mean difference (mm) for test minus control.

.

.

.

.

.

A

Hangorsky & Bissada

Dorfman et al.

Dorfman et al.

Kennedy et al

Subtotal (I-squared = 96.6%, p = 0.000)

B

Edel

Subtotal (I-squared = .%, p = .)

C

Mohammadi et al.


D

Harris

Harris

McGuire & Nunn

McGuire et al.


E

Gher et al.


author

1980

1980

1982

1984

1974

2007

2001

2001

2005

2008

1980

year_of_publication

APF/vestibuloplasty plus autogenous tissue





APF/vestibuloplasty plus allogenic graft






level4_act

no treatment/scaling and root planing





vestibuloplasty






level4_co1

1.99 (1.29, 2.69)

4.58 (4.54, 4.62)

4.90 (4.80, 5.00)

4.60 (4.55, 4.65)

4.49 (4.28, 4.71)

0.34 (-0.45, 1.13)

0.34 (-0.45, 1.13)

0.70 (-0.14, 1.54)

0.70 (-0.14, 1.54)

-0.10 (-1.24, 1.04)

0.70 (-0.39, 1.79)

-1.19 (-1.46, -0.92)

-2.06 (-2.24, -1.88)

-0.85 (-1.71, 0.01)

1.22 (0.71, 1.73)

1.22 (0.71, 1.73)

difference (95% CI)

mean

1.99 (1.29, 2.69)

4.58 (4.54, 4.62)

4.90 (4.80, 5.00)

4.60 (4.55, 4.65)

4.49 (4.28, 4.71)

0.34 (-0.45, 1.13)

0.34 (-0.45, 1.13)

0.70 (-0.14, 1.54)

0.70 (-0.14, 1.54)

-0.10 (-1.24, 1.04)

0.70 (-0.39, 1.79)

-1.19 (-1.46, -0.92)

-2.06 (-2.24, -1.88)

-0.85 (-1.71, 0.01)

1.22 (0.71, 1.73)

1.22 (0.71, 1.73)

difference (95% CI)

mean

favors control group favors test/active group

0-4 -2 0 2 4

Abbreviations: APF = apically positioned flap. CI = confidence interval.

A: I-squared (percentage variation attributable to heterogeneity) = 96.6%; test for overall effect: z = 41.37, p = 0.000. B: significance test: z = 0.84, p = 0.401. C: significance test: z = 1.64, p = 0.101. D: I-squared = 94.6%; test for overall effect: z = 1.95, p = 0.052. E: significance test: z = 4.69, p = 0.000.

Figure 4. Meta-analysis of percentage shrinkage of keratinized tissue. Mean difference (%) for test minus control.

Overall (I-squared = 95.1%, p = 0.000)

McGuire & Nunn

Wei et al.

author

2005

2000

year_of_publication

HF-DDS

ADMG

graft_1

FGG

FGG

control_1

28.41 (23.56, 33 26)

23.70 (18.44, 28 96)

55.00 (42.50, 67 50)

difference (95% CI)

mean

28.41 (23.56, 33.26)

23.70 (18.44, 28.96)

55.00 (42.50, 67.50)

difference (95% CI)

mean

favors test/active group favors control group 0-10 0 20 40 60 80 100

Abbrevations: CI = confidence interval; ADMG = acellular dermal matrix allograft; FGG = free gingival graft; HF-DDS = human fibroblast-derived dermal substitute. I-squared (percentage variation attributable to heterogeneity) = 95.1%; test for overall effect: z = 11.49, p = 0.000.

Figure 5 A to E. Meta-analyses of width of attached gingiva at end of study. Mean difference (mm) for test minus control.

.

.

.

.

.

A

Hangorsky & Bissada

de Trey & Bernimoulin

Dorfman et al.

Dorfman et al.

Kennedy et al


B

Fagan & Freeman

Fagan

Fagan


C

Mohammadi et al.


D

McGuire et al.


E

Gher et al.


author

1980

1980

1980

1982

1984

1974

1975

1975

2007

2008

1980

year_of_publication












level4_act






vestibuloplasty

vestibuloplasty

vestibuloplasty

vestibuloplasty



level4_co1

1.82 (1.11, 2.53)

3.29 (3.13, 3.45)

4.35 (4.30, 4.40)

4.50 (4.40, 4.60)

4.50 (4.45, 4.55)

3.94 (3.64, 4.23)

0.82 (0.61, 1.03)

1.26 (0.89, 1.63)

0.37 (-0.08, 0.82)

0.83 (0.42, 1.25)

0.70 (-0.10, 1.50)

0.70 (-0.10, 1.50)

-1.52 (-1.73, -1.31)

-1.52 (-1.73, -1.31)

1.17 (0.61, 1.73)

1.17 (0.61, 1.73)

difference (95% CI)

mean

1.82 (1.11, 2.53)

3.29 (3.13, 3.45)

4.35 (4.30, 4.40)

4.50 (4.40, 4.60)

4.50 (4.45, 4.55)

3.94 (3.64, 4.23)

0.82 (0.61, 1.03)

1.26 (0.89, 1.63)

0.37 (-0.08, 0.82)

0.83 (0.42, 1.25)

0.70 (-0.10, 1.50)

0.70 (-0.10, 1.50)

-1.52 (-1.73, -1.31)

-1.52 (-1.73, -1.31)

1.17 (0.61, 1.73)

1.17 (0.61, 1.73)

difference (95% CI)

mean

favors control group favors test/active group

0-2 0 2 4

Abbreviations: CI = confidence interval; APF = apically positioned flap.

A: I-squared (percentage variation attributable to heterogeneity) = 98.4%; test for overall effect: z = 25.83, p = 0.000. B: I-squared = 78.4%; test for overall effect: z = 3.91, p = 0.000. C: significance test: z = 1.72, p = 0.085. D: significance test: z = 14.33, p = 0.000. E: significance test: z = 4.08, p = 0.000.

Table 1: Abbreviations used in text, figures and tables. ADMG Acellular dermal matrix graft APF Apically positioned flap APF/V Apically positioned flap/vestibuloplasty BCT Bilayered cell therapy CCT Controlled clinical trial CI Confidence interval FGG Free gingival graft HA Hydroxylapatite bone substitute HF-DDS Human fibroblast-derived dermal substitute NA Not applicable RCT Randomized controlled clinical trial SCTG Subepithelial connective tissue graft SD Standard deviation TEMG Tissue-engineered mucosal graft WMD Weighted mean differences

Table 2: Excluded studies.

author year reason for exclusion Obwegeser 1967 description of technique Möller & Jölst 1972 only descriptive histology Dreeskamp et al. 1973 no reported data on keratinized tissue Dordick et al. 1976 no reported data on width of keratinized tissue Flores de Jacoby & Mutschelknauss 1978 no control group Rozencweig 1976 insufficient follow-up data; follow-up two months only Yukna et al. 1977 insufficient number of patients (4) Ackermann et al. 1980 fully edentulous patients Bachmann & Bernimoulin 1980 no control group Haase et al. 1980 retrospective study Krekeler et al. 1980 no control group Löst 1980 no data on keratinized tissue Ouhayoun et al. 1983 no measurements for control group; only descriptive histology Härle 1987 no data on keratinized tissue Schramm-Scherer & Linder 1987 no reported outcomes on width of keratinized tissue Sbordone et al. 1988 root coverage procedure Mercier et al. 1992 no control group; no data on keratinized tissue Raghoebar et al. 1995 only descriptive histology Lauer et al. 1996 simulataneously with implant placement Shulman 1996 follow-up only six weeks; no control group Al-Mahdy Al-Belasy 1997 no control group Fröschl & Kerscher 1997 fully edentulous patients Carnio & Miller 1999 no control group Lauer & Schimming 2001 no control group; only descriptive data Wei et al. 2002 only descriptive histology Orsini et al. 2004 no measurements for control group Sezer et al. 2004 fully edentulous patients de Almeida et al. 2005 no reported treatment outcomes on width of keratinized tissue, volume or patient-centered outcomes Luczyszyn et al. 2005 control group does not use soft tissue augmentation Griffin et al. 2006 no data on keratinized tissue Wessel & Tatakis 2008 no reported outcomes on width of keratinized tissue

Table 3: Included studies part 1: augmentation of keratinized tissue

author year of

publication study design

test treatment control 1 treatment

control 2 treatment

control 3 treatment

follow-up

period (weeks)

total number

of patients

total number of sites

number of sites

test group

number of sites control

1 group


2 group


3 group

Diedrich et al. 1972 CCT

vestibuloplasty with releasing incision vestibuloplasty 17 15 30 15 15

Richter et al. 1973 CCT

vestibuloplasty without suturing vestibuloplasty 35 12 24 12 12

Edel 1974 Cohort Study

APF plus SCTG (method 1)


APF plus SCTG (method 3) 26 8 14 6 6 2

Fagan & Freeman 1974 CCT APF plus FGG APF 12 10 22 10 12

Matthiessen & Diedrich 1974 CCT

vestibuloplasty extended into horizontal part of ridge vestibuloplasty 17 10 20 10 10

Fagan 1975 CCT APF plus FGG APF 12 5 10 5 5

Dordick et al. 1976 RCT

APF with releasing incision plus FGG APF plus FGG 26 60 30 30

Lange & Flores de Jacoby 1976 CCT

vestibuloplasty with releasing incision vestibuloplasty 208 8 16 8 8

Schoo & Coppes 1976

Cohort Study

APF plus lyoph. dura mater APF plus FGG 104 58 84 16 68

James & McFall 1978 CCT

vestibuloplasty/APF with releasing incision plus FGG

vestibuloplasty/APF plus FGG 12 14 28 14 14

de Trey & Bernimoulin 1980 CCT APF plus FGG no treatment 14 12 24 12 12

Dorfmann et al. 1980 RCT APF plus FGG no treatment 104 92 184 92 92

Gher et al. 1980 Cohort Study

vestibuloplasty/APF plus FDS with fenestration

vestibuloplasty/APF plus FDS without fenestration 12 31 148 76 72

Hangorsky & Bissada 1980 CCT

vestibuloplasty/APF plus FGG no treatment 52-416 34 80 40 40

Lange et al. 1981 CCT

vestibuloplasty according to Schmid & Mörmann

vestibuloplasty according to Plagmann 26 15 30 15 15

Mörmann et al. 1981 CCT

APF plus FGG (scalpel)

APF plus FGG (mucotom very thin)

APF plus FGG (mucotom thin)

APF plus FGG (mucotom intermediate) 52 34 89 19 11 29 30

Dorfmann et al. 1982 RCT APF plus FGG

scaling and root planing 208 21 42 21 21

Marxer et al. 1982 RCT

vestibuloplasty/APF plus FGG

vestibuloplasty according to Edlan & Mejchar 52 16 80 40 40

Pöllmann & Scherer 1983

Cohort Study

vestibuloplasty/APF plus lyophylised dura mater vestibuloplasty

vestibuloplasty/APF plus FGG 26 45 45 25 9 11

Kennedy et al. 1985 RCT


scaling and root planing 312 32 64 32 32

Wei et al. 2000 RCT APF plus ADMG APF plus FGG 26 12 12 6 6

Harris 2001 RCT vestibuloplasty/APF plus ADMG


vestibuloplasty/APF plus SCTG 13 45 45 15 15 15

McGuire & Nunn 2005 RCT

vestibuloplasty/APF plus HF-DDS


Mohammadi et al. 2007 RCT

vestibuloplasty/APF plus TEMG vestibuloplasty/APF 13 9 18 9 9

McGuire et al. 2008 RCT

vestibuloplasty/APF plus BCT


CCT = controlled clinical trial; RCT = randomized controlled clinical trial; APF = apically positioned flap; SCTG = subepithelial connective tissue graft; FGG = free gingival graft; ADMG = acellular dermal matrix graft; FDS = freeze-dried skin allograft; HF-DDS = human fibroblast - derived dermal substitute; TEMG = tissue-engineered mucosal graft; BCT = bilayered cell therapy

Table 4: Included studies part 2: augmentation of soft tissue volume

author year of


test treatment

control 1 treatment

control 2 treatment

follow-up period

(weeks)

total number

of patients

total number of

sites

number of patients

test group

number of patients control 1

group

number of patients control 2

group

Allen et al. 1985 Cohort study SCTG HA 24 21 26 14 12

Studer et al. 2000 Cohort study SCTG FGG no treatment 14 30 30 12 12 6

Batista et al. 2001 Case series ADMG 27 8 18 18

SCTG = subepithelial connective tissue graft; ADMG = acellular dermal matrix graft; HA = hydroxylapatite bone substitute; FGG = free gingival graft

Table 5: Characteristics of included studies: width of keratinized tissue

author year of


total number

of patients

total number

of sites

number of

patients test

number of

sites test

number of

patients control

1

number of

sites contol

1

number of

patients control

2

number of

sites control2

follow-up

period (weeks) test treatment

control 1 treatment

control 2 treatment

Diedrich et al. 1972 CCT 15 30 15 15 15 15 17

vestibuloplasty with releasing incision vestibuloplasty

Edel 1974 Cohort study 8 14 6 6 2 26




Dorfman et al. 1980 RCT 92 184 92 92 92 92 104 APF plus FGG no treatment

Gher et al. 1980 Cohort study 31 148 76 72 8


vestibuloplasty/APF plus FDS without fenestration

Hangorsky & Bissada 1980 CCT 34 40 34 40 34 40 52-416

vestibuloplasty/APF plus FGG no treatment

Lange et al. 1981 CCT 15 30 15 15 15 15 26

vestibuloplasty according to Schmid & Mörmann

vestibuloplasty according to Plagmann

Dorfman et al. 1982 RCT 21 42 21 21 21 21 208 APF plus FGG

scaling and root planing

Kennedy et al. 1985 RCT 32 64 32 32 32 32 312



Harris 2001 RCT 45 45 15 15 15 15 15 15 13 vestibuloplasty/APF plus ADMG


vestibuloplasty/APF plus SCTG

McGuire & Nunn 2005 RCT 22 44 22 22 22 22 52

vestibuloplasty/APF plus HF-DDS


Mohammadi et al. 2007 RCT 9 18 9 9 9 9 13

vestibuloplasty/APF plus TEMG vestibuloplasty/APF

McGuire et al. 2008 RCT 25 50 25 25 25 25 26



CCT = controlled clinical trial; RCT = randomized controlled clinical trial; APF = apically positioned flap; SCTG = subepithelial connective tissue graft; FGG = free gingival graft; FDS = freeze-dried skin allograft; ADMG = acellular dermal matrix graft; HF-DDS = human fibroblast-derived dermal substitute; TEMG = tissue-engineered mucosal graft; BCT = bilayered cell therapy.

author treatment indication

outcome measure

baseline test SD

post-surgery

test SD change

test

change test SD

baseline control

1 SD

post-surgery control

1 SD

change control

1

change control

SD

Diedrich et al. vestibuloplasty

keratinized tissue (mm) 3.5 5.6 2.1 3.8 5.6 1.8

Edel

inadequate width of keratinized tissue

keratinized tissue (mm) 1.33 0.24 4.42 0.67 1.58 0.34 4.08 0.73

Dorfman et al.

inadequate width of attached gingiva


Gher et al.



Hangorsky & Bissada


keratinized tissue (mm) 4.9 1.67 2.91 1.51

Lange et al. vestibuloplasty

keratinized tissue (mm) 23.6 26.7

Dorfman et al.



Kennedy et al.

inadequate width of AG


Harris


keratinized tissue (mm) 0.6 0.87 4.7 1.92 4.1 1.79 0.8 0.59 4.8 1.16 4.1 1.25

McGuire & Nunn

lack of keratinized gingiva


Mohammadi et al.


keratinized tissue (mm) 1.3 0.4 4.1 1 1.5 0.4 3.4 0.8

McGuire et al.


keratinized tissue (mm) 1.07 0.18 2.4 0.32 1.33 0.38 1.17 0.18 4.46 0.32 3.29 0.38

author

baseline control

2 SD

post-surgery control

2 SD

change control

2

effect of device vs. control 1

effect of device

vs. control 2

effect of control 1

vs. control 2 comments

Diedrich et al.

no difference

Edel 1.5 0 3.5 0 significant

statistics pre- to postoperative

Dorfman et al. significant

statistics postoperative

Gher et al. significant 8-week results

Hangorsky & Bissada significant

Lange et al.

Dorfman et al. significant


Kennedy et al. significant

Harris 0.4 0.47 4 0.99 3.6 not significant

not significant

not significant

statistics for change

McGuire & Nunn significant


Mohammadi et al. significant


McGuire et al.

signisficant negative

Table 6: Characteristics of included studies: shrinkage of keratinized tissue

author year of


total number

of patients


number of

patients test

number of sites

test

number of

patients control


follow-up

period (weeks)

test treat-ment

control treat-ment

treat-ment

indication outcome measure

outcome test

SD test

outcome control

SD control

effect device

vs. control

Wei et al. 2000 RCT 12 12 6 6 6 6 26 ADMG FGG

keratinized gingiva <1mm

percentage shrinkage of keratinized tissue (%) 71 10 16 12 significant

McGuire & Nunn 2005 RCT 22 44 22 22 22 22 52

HF-DDS FGG

lack of keratinized gingiva

percentage shrinkage of keratinized tissue (%) 45.5 8.9 21.8 8.9 significant

RCT = randomized controlled clinical trial; ADMG = acellular dermal matrix graft; HF-DDS = human fibroblast - derived dermal substitute; FGG = free gingival graft; SD = standard deviation.; vs. = versus.

Table 7: Characteristics of included studies: width of attached gingiva

author year of


total number

of patients

total number

of sites

number of

patients test

number of

sites test

number of

patients control

number of

sites control

follow-up

period (weeks) test treatment

control treatment

treatment indication

outcome measure

Diedrich et al. 1972 CCT 15 30 15 15 15 15 17

vestibuloplasty with releasing incision vestibuloplasty vestibuloplasty

width of attached gingiva (mm)

Richter et al. 1973 CCT 12 24 12 12 12 12 35

vestibuloplasty without suturing vestibuloplasty vestibuloplasty


Fagan & Freeman 1974 CCT 10 22 10 10 10 12 12 APF plus FGG APF



Matthiessen & Diedrich 1974 CCT 10 20 10 10 10 10 17

vestibuloplasty extended into horizontal part of ridge vestibuloplasty vestibuloplasty


Fagan 1975 CCT 5 10 5 5 5 5 12 APF plus FGG APF



Fagan 1975 CCT 5 10 5 5 5 5 12 APF plus FGG APF no attached gingiva


Lange & Flores de Jacoby 1976 CCT 8 16 8 8 8 8 208

vestibuloplasty with releasing incision vestibuloplasty vestibuloplasty


de Trey & Bernimoulin 1980 CCT 12 24 12 12 12 12 14 APF plus FGG no treatment

attached gingiva <1mm


Dorfman et al. 1980 RCT 92 184 92 92 92 92 104 APF plus FGG no treatment



Gher et al. 1980 Cohort study 31 148 76 72 8


vestibuloplasty/APF plus FDS without fenestration



Hangorsky & Bissada 1980 CCT 34 40 34 40 34 40 52-416

vestibuloplasty/APF plus FGG no treatment



Dorfman et al. 1982 RCT 21 42 21 21 21 21 208 APF plus FGG




Kennedy et al 1985 RCT 32 64 32 32 32 32 312





Wei et al. 2000 RCT 12 12 6 6 6 26 APF plus ADMG APF plus FGG attached gingiva <1mm


Mohammadi et al. 2007 RCT 9 18 9 9 9 9 13

vestibuloplasty/APF plus TEMG vestibuloplasty/APF



McGuire et al. 2008 RCT 25 50 25 25 25 25 26





CCT = controlled clinical trial; RCT = randomized controlled clinical trial; APF = apically positioned flap; FGG = free gingival graft; ADMG = acellular dermal matrix graft; FDS = freeze-dried skin allograft; TEMG = tissue-engineered mucosal graft; BCT = bilayered cell therapy; SD = standard deviation.; vs. = versus.

author baseline

test SD post-

surgery test SD change

test

change test SD

baseline control SD

post-surgery control SD

change control

change control

SD

effect of device

vs. control 1

effect of

device vs.

control 2 comments

Diedrich et al. 1.3 4.9 3.7 1.6 5 3.4

Richter et al. 1.5 4.3 2.8 1.2 3.8 2.6

Fagan & Freeman 0.11 0.05 4.31 0.26 4.2 0.25 0.4 0.14 3.49 0.24 3.1 0.26

Matthiessen & Diedrich 1.6 5.2 1.6 6

Fagan 0.13 0.08 4.5 0.41 4.37 0.38 0.8 0.25 4.13 0.3 3.33 0.46 not significant

Fagan 0.1 0.02 4.13 0.25 4.06 0.25 0 2.87 0.34 2.87 0.34 significant

Lange & Flores de Jacoby 4 3.5

de Trey & Bernimoulin 0.46 0.08 3.67 0.27 0.74 0.14 0.38 0.11 significant

Dorfman et al. 0.35 0.07 4.71 0.21 0.33 0.05 0.36 0.07 significant

statistics postoperatively

Gher et al. 0.91 0.98 5.18 1.82 0.71 0.97 4.01 1.67 significant

Hangorsky & Bissada 3.53 1.79 1.71 1.42 significant

Dorfman et al. 0.3 0.06 4.8 0.23 0.3 0.07 0.3 0.07 significant


Kennedy et al 0.3 0.1 5 0.1 0.3 0.1 0.5 0.1 significant

Wei et al. 0.68 0.26 3.25 0.89 2.59 0.92 0.57 0.41 6.15 0.49 5.57 0.44 significant

Mohammadi et al. 0.2 0.4 3 1 0.3 0.4 2.3 0.7 significant


McGuire et al. 0.26 0.14 1.1 0.38 0.85 0.37 0.24 0.14 2.62 0.37 2.37 0.37 significant

Table 8: Characteristics of the included studies: soft tissue volume

author year of


total number

of patients


number of

patients control

1


1

number of

patients control

2


2

number of

patients test

number of sites

test

follow-up

period (weeks)

test treatment

control 1 treatment

control 2 treatment

type of defect

outcome measure

Allen et al. 1985

Cohort study 21 26 12 14 24 SCTG

Hydroxyl-apatite

localized alveolar ridge defect

shrinkage (descriptive)

Studer et al. 2000

Cohort study 30 30 12 12 6 6 12 12 14 SCTG FGG

untreated defect


soft tissue volume (mm3)

Batista et al. 2001

Case series 8 18 8 18 27 ADMG


gain in horizontal ridge width (mm)

Batista et al. 2001



gain in vertical ridge height (mm)

Batista et al. 2001



% shrinkage horizontal

SCTG = subepithelial connective tissue graft; ADMG = acellular dermal matrix graft; FGG = free gingival graft; NA = not applicable; SD = standard deviation.; vs. = versus.

author outcome

test SD test

outcome control

1

SD control

1

outcome control

2

SD control

2

effect of test vs.

control 1

effect of test vs.

control 2

effect of control 1

vs. control 2 comments

Allen et al.

14 of 14 sites: shrinkage within first 4-6 weeks, then stable for 3 years

10 of 12 sites: no shrinkage NA

not mentioned how measurements were performed

Studer et al. 159 80 104 31 6 5.4 significant significant significant

Batista et al. 1.72 0.59 NA

Batista et al. 0.61 0.77 NA

Batista et al. 41.4 NA

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