A Systematic Review Assessing Soft Tissue Augmentation Techniques

Daniel S.
Thoma A systematic review assessing soft

Goran I. Benić
Marcel Zwahlen
tissue augmentation techniques
Christoph H. F. Hämmerle
Ronald E. Jung
Authors’ affiliations: Key words: allogenic dermal matrix, free gingival graft, human fibroblast-derived dermal
Daniel S. Thoma, Goran I. Benić, Marcel Zwahlen, substitute, keratinized tissue, soft tissue augmentation, soft tissue volume, subepithelial
Christoph H. F. Hämmerle, Ronald E. Jung, Clinic
for Fixed and Removable Prosthodontics and Dental connective tissue graft, vestibuloplasty
Material Science, University of Zurich, Zurich,
Switzerland
M. Zwahlen, Institute of Social and Preventive
Abstract
Medicine, University of Bern, Bern, Switzerland 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 one method superior
Correspondence to:
Daniel S. Thoma over others for augmentation and stability of the augmented soft tissue in terms of
Clinic for Fixed and Removable Prosthodontics and increasing the width of keratinized tissue (part 1) and gain in soft tissue volume (part 2).
Dental Material Science
University of Zurich Methods: A Medline search was performed for human studies focusing on augmentation of
Plattenstrasse 11 keratinized tissue and/or soft tissue volume, and complemented by additional hand searching.
CH-8032 Zurich
Relevant studies were identified and statistical results were reported for meta-analyses
Switzerland
Tel.: þ 41 44 634 32 57 including the test minus control weighted mean differences with 95% confidence intervals,
Fax: þ 41 44 634 43 05 the I-squared statistic for tests of heterogeneity, and the number of significant studies.
e-mail: [email protected]
Results: Twenty-five (part 1) and three (part 2) studies met the inclusion criteria; 14 studies
Conflicts of interest: (part 1) were eligible for comparison using meta-analyses. An apically positioned flap/
The authors declare no conflicts of interest. vestibuloplasty (APF/V) procedure resulted in a statistically significantly greater gain in
keratinized tissue than untreated controls. APF/V plus autogenous tissue revealed statistically
significantly more attached gingiva compared with untreated controls and a borderline
statistical significance compared with APF/V plus allogenic tissue. Statistically significantly
more shrinkage was observed for the APF/V plus allogenic graft compared with the APF/V
plus autogenous tissue. Patient-centered outcomes did not reveal any of the treatment
methods to be superior regarding postoperative complications. The three 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 with 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.
Date: Soft tissue augmentation with autogenous well as to increase soft tissue volume.
Accepted 20 May 2009
grafts is a widely used procedure in a Various studies suggested associations be-
To cite this article: variety of disciplines in dentistry. It is tween an adequate width of keratinized
Thoma DS, Benić GI, Zwahlen M, Hämmerle CHF,
Jung RE. A systematic review assessing soft tissue indicated in partially and fully edentulous tissue, higher survival rates of dental im-
augmentation techniques. patients to augment areas with a lack of or plants, health of the peri-implant mucosa,
Clin. Oral Impl. Res. 20 (Suppl. 4), 2009; 146–165.
doi: 10.1111/j.1600-0501.2009.01784.x a reduced width of keratinized tissue, as and an improved esthetic outcome (Adell
146 c 2009 John Wiley & Sons A/S

Thoma et al Soft tissue grafting: a systematic review
et al. 1986; Artzi et al. 1993; Langer 1996). and materials primarily of allogenic origin lished from January 1, 1966 up to August
However, two recent reviews concluded have been developed. Among the first pro- 31, 2008 in the Dental literature. The search
that there is insufficient or even a lack of ducts introduced in mucogingival surgery was limited to the English, French, German,
evidence regarding the influence of the were freeze-dried skin allografts, initially and Italian language. The search was com-
width of keratinized tissue on the survival used as a replacement for FGGs in combi- plemented by manual searches of the refer-
rate and future mucosal recessions (Espo- nation with an APF for the augmentation ence list of all selected full-text articles.
sito et al. 2007; Cairo et al. 2008). of keratinized tissue (Yukna & Sullivan Additionally, full-text articles of reviews
With respect to teeth, a certain amount of 1978). Later in the 1980s, allogenic dermal published between January 2005 and
keratinized tissue has been considered ne- substitutes like the acellular dermal matrix August 2008 were obtained. An additional
cessary to maintain periodontal health and graft (ADMG; Allodermt, Life Cell hand search was performed searching for
to prevent gingival recession (Nabers 1966; Corporation, The Woodlands, TX, USA), relevant studies by screening these reviews.
Sullivan & Atkins 1969). It was also con- originally developed for covering full-thick-
cluded that for the maintenance of gingival ness burn wounds (Wainwright 1995), have Search terms
health 2 mm of keratinized gingiva is ade- been used to increase keratinized tissue, for The following search terms were selected:
quate (Lang & Löe 1972). Because an ade- a root coverage procedure, to deepen the ‘acellular dermal matrix’ OR ‘dermal ma-
quate amount of keratinized tissue has not vestibular fornix, and to augment localized trix allograft’ OR ‘alloderm’ OR ‘kerati-
been defined yet, the decision to augment alveolar defects (Wei et al. 2000; Aichel- nized gingiva’ OR ‘keratinized tissue’ OR
the width of keratinized gingiva around mann-Reidy et al. 2001; Batista et al. 2001; ‘soft tissue graft’ OR ‘subepithelial connec-
dental implants and teeth still depends on Harris 2003). tive tissue graft’ OR ‘connective tissue’ OR
the clinician’s choice and the planned surgi- Recent techniques follow the guidelines of ‘free gingival graft’ OR ‘human fibroblast-
cal and prosthetic treatment. Historically, tissue engineering. Tissue-engineered pro- derived dermal substitute’ OR ‘dermagraft’
the methods to augment keratinized tissue ducts are based on isolated cells or cell OR ‘apligraf’ OR ‘gingival autograft’ OR
included: (i) an apically positioned flap substitutes, tissue-inducing substances (bio- ‘attached gingiva’ OR ‘attached mucosa’
(APF); (ii) an APF in combination with logic mediators), and scaffolds of natural or OR ‘keratinized mucosa’ OR ‘soft tissue
autogenous tissue, and (iii) an APF in com- synthetic origin (Langer & Vacanti 1993). In augmentation’ OR ‘soft tissue transplanta-
bination with allogenic tissue (Friedman contrast to ADMG, newer grafts like the tion’ OR ‘vestibuloplasty’ OR ‘ridge aug-
1962; Edel 1974; Yukna & Sullivan 1978). human fibroblast-derived dermal substitute mentation’ OR ‘soft tissue correction.’ The
s
Autogenous soft tissue grafting procedures (HF-DDS, Dermagraft , Advanced Tissue search was limited to ‘human trial’ (MeSH
have also been proposed to surgically correct Sciences Inc., La Jolla, CA, USA) and a term, clinical studies) and ‘Dental Jour-
s
localized alveolar defects, as preprosthetic human skin equivalent (BCT, Apligraf , nals’. Additionally, the MeSH terms ‘clin-
site development, and as ridge preservation Organogenesis, Canton, MA, USA) include ical trial,’ ‘comparative study,’ ‘controlled
procedures (Seibert 1983; Studer et al. 2000; a cellular component. Both grafts have been clinical trial,’ ‘randomized controlled trial,’
Jung et al. 2004; Prato et al. 2004). As for the investigated in clinical trials in comparison ‘meta-analysis,’ and ‘review’ were used.
augmentation of keratinized tissue, tradi- with autogenous soft tissue to increase the
tionally, the free gingival graft (FGG) and width of keratinized tissue (McGuire &
Inclusion criteria
the subepithelial connective tissue graft Nunn 2005; McGuire et al. 2008).
The applied inclusion criteria were differ-
(SCTG) have been described to increase Since techniques and materials have
ent for studies dealing with gain of kerati-
soft tissue volume (Seibert 1983). changed quite extensively over the last
nized tissue or gain of soft tissue volume.
The disadvantages of using autogenous decades, there is a lack of information and
tissue are mainly due to the harvesting a strong need to critically assess the dental
procedure, which leads to a prolonged heal- literature for optimized procedures and Part 1: augmentation of keratinized tissue
ing time at the donor site and therefore to grafts in terms of soft tissue augmentation. Any prospective cohort study with at least
an increased patient’s morbidity (Farnoush The aim of the present review was to five patients was included. A follow-up
1978; Griffin et al. 2006). Patients often systematically assess the dental literature period of at least 3 months was required.
complain about pain and numbness for in terms of soft tissue grafting techniques. The reported treatment outcomes had to
several weeks after the surgery (Del Pizzo The focused question was whether one include either clinical and/or histological
et al. 2002; Soileau & Brannon 2006). On method is superior over others for augmen- measures of the width of keratinized tissue
the other hand, anatomical and individual tation and stability of the augmented soft (test) and the control(s). The primary out-
limitations exist. Depending on the shape tissue in terms of (i) increasing the width of come of the studies had to be localized
of the palatal vault, the patient’s sex and keratinized tissue (part 1) and (ii) gain in augmentation of keratinized tissue.
age, the quantity and quality of tissue that soft tissue volume (part 2).
can be retrieved varies. The location of the Part 2: augmentation of soft tissue volume
palatal vessels and nerves further limits the Material and methods For studies focusing on soft tissue volume
total amount that is available for grafting gain, any prospective case series with at
procedures (Soileau & Brannon 2006). Search strategy least five patients was included. The mini-
In order to overcome these issues with A Medline (PubMed) search was performed mal follow-up time was 3 months. The
autogenous tissue, alternative techniques for human studies, including articles pub- reported treatment outcomes had to
c 2009 John Wiley & Sons A/S

147 | Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146–165
include either clinical and/or histological Table 1. Abbreviations used in text, figures, and tables
measures of the soft tissue volume. ADMG Acellular dermal matrix graft
APF Apically positioned flap
APF/V Apically positioned flap/vestibuloplasty
Exclusion criteria BCT Bilayered cell therapy
Studies not meeting all inclusion criteria CCT Controlled clinical trial
were excluded from the review. Publica- CI Confidence interval
tions dealing with the following topics FGG Free gingival graft
HA Hydroxylapatite bone substitute
were also excluded: in vitro studies, pre- HF-DDS Human fibroblast-derived dermal substitute
clinical (animal) studies, studies dealing NA Not applicable
with the treatment of recession defects, RCT Randomized-controlled clinical trial
and studies augmenting soft tissue in fully SCTG Subepithelial connective tissue graft
SD Standard deviation
edentulous patients. TEMG Tissue-engineered mucosal graft
WMD Weighted mean differences
Selection of studies
Titles derived from this broad search were
independently screened by two authors
(D.S.T., G.I.B.) based on the inclusion cri-
teria. Disagreements were resolved by dis-
cussion. Cohen’s k coefficient was used as a
measure of agreement between the two margo gingivae
readers. Following this, abstracts of all titles
agreed on by both authors were obtained,
free gingiva /
and screened for meeting the inclusion cri- periodontal
teria. If no abstract was available in the probing depth
database, the abstract of the printed article keratinized cemento-enamel junction

tissue
was used. The selected articles were then attached
obtained in full text. If the title and abstract gingiva
did not provide sufficient information re-

garding the inclusion criteria, the full report
was obtained as well. Again, disagreements muco-gingival junction
were resolved by discussion.
Finally, the selection based on inclusion/
exclusion criteria was made for the full-text
Fig. 1. Schematic drawing of the parameters analyzed at the dento-gingival unit.
articles. For this purpose, ‘Material and
methods,’ and ‘Results’ of these studies
were screened. This step was again carried
out independently by two readers. Dis- graft control group(s), type of treatment, number of sites control group(s), follow-up
agreements were resolved by discussion. width of keratinized tissue, width of at- period, graft test group, graft control
tached gingiva, shrinkage of attached gin- group(s), type of defect, and gain/change
Data extraction giva, augmented area, shrinkage of in volume.
Two reviewers independently extracted the augmented area, width of graft, shrinkage
data using data extraction tables. Any dis- of graft, depth of vestibulum, as well as Statistical analysis
agreements were resolved by discussion patient-reported outcomes (postoperative Based on the reported treatment modalities
aiming for a consensus. For abbreviations bleeding, swelling, pain, toleration of pro- and the outcomes measured, a meta-ana-
used throughout the text, tables, and fig- cedure, and esthetics). Smoking status was lysis was performed for 14 studies for part 1
ures please refer to Table 1. only assessed in one study and therefore (keratinized tissue) for three types of con-
not indicated in the tables. Figure 1 repre- tinuous outcome measures: (1) mean
Part 1: keratinized tissue sents a schematic drawing of the analyzed change in the width of keratinized tissue
For studies on keratinized tissue augmen- parameters. in mm from baseline to the end of the
tation, information on the following para- study (10 studies), (2) percentage shrinkage
meters was extracted: author(s), year of Part 2: augmentation of soft tissue volume of width of keratinized tissue in mm from
publication, study design, total number of Information on the following parameters baseline to follow-up (two studies), and (3)
patients, number of patients in the test was extracted: author(s), year of publica- mean width of attached gingiva at follow-
group, number of patients in the control tion, study design, total number of pa- up (10 studies). The outcome of interest
group(s), total number of sites, number of tients, number of patients test group, was, for each study, the postintervention
sites test group, number of sites control number of patients control group(s), total mean difference between the test and the
group(s), follow-up period, graft test group, number of sites, number of sites test group, control group. To be able to perform a
148 | Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146–165 c 2009 John Wiley & Sons A/S

meta-analysis on mean differences, the size first electronic search:

of the test and control group and standard 1471 titles
deviations of measures of interest needed
to be available from the study reports.
inter-reader agreement
Forest plots were produced to graphically k = 0.82 ± 0.02
depict study-specific mean differences and
summary estimates obtained from the
meta-analyses. We report 95% confidence
independently selected by 2 reviewers
intervals (CI), Cochran’s Q statistic, and and agreed by both: 115 titles
the I-squared statistic to test for and quan- abstracts obtained
tify heterogeneity. The I-squared measure

describes the proportion of total variation
in study estimates that is due to hetero- inter-reader agreement
k = 0.81 ± 0.05
geneity (Higgins & Thompson 2001).
Whenever substantial heterogeneity was
present, a random-effects meta-analysis
was performed. Meta-analyses were per-
independently selected by 2 reviewers
formed using the user-written ‘metan’ and agreed by both: 58 abstracts
command for use in Stata (StataCorp LP, full text obtained
College Station, TX, USA).
Results
keratinized tissue: 48 soft tissue volume: 4 review: 6
Study characteristics
The electronic search identified a total of
1471 titles (for details, refer to Fig. 2). From
assessing the titles, 1356 were excluded further handsearching 7 articles
(references of full text articles)
(inter-reader agreement k ¼ 0.82 0.02).
The resulting number of abstracts obtained
was 115, out of which 67 were excluded excluded: 1
(inter-reader agreement k ¼ 0.81 0.05).

excluded: 30
Sixty-five full-text articles were obtained
including seven studies found through final number of studies included final number of studies included
hand searching. Finally, 25 (keratinized keratinized tissue: 25 soft tissue volume: 3
tissue) and three (soft tissue volume) arti- Fig. 2. Search strategy.
cles met the inclusion criteria.
Exclusion of studies refers to clinical studies dealing with ‘soft flap/vestibuloplasty (APF/V) in combina-
The reasons for excluding studies (n ¼ 31, tissue volume’ (part 2; three studies). tion with autogenous tissue (FGG, SCTG),
Table 2) after the full text was obtained were: and APF/V in combination with allogenic
no reported or insufficient clinical, or histo- grafts (ADMG, BCT, FDS, and HF-DDS).
Part 1: keratinized tissue
logical treatment outcomes (e.g. only de- The mean follow-up period was 63 weeks
scriptive presentation of results; n ¼ 13), no Treatment outcomes (12–416 weeks). The reason for treating the
control group (n ¼ 8), fully edentulous pa- Patient-based treatment outcomes on aug- patients included a lack of or an inadequate
tients (n ¼ 3), an insufficient number of mentation of keratinized tissue retrieved width of attached gingiva/keratinized tis-
patients (n ¼ 1), retrospective study (n ¼ 1), from 25 included studies are presented in sue (22 studies) or vestibuloplasty (three
insufficient follow-up data (n ¼ 1), descrip- Tables 3 and 5–7. Ten studies were de- studies). In summary, 14 studies were
tion of technique (n ¼ 1), root coverage pro- signed as randomized-controlled clinical eligible for comparison using meta-ana-
cedure (n ¼ 1), retrospective study (n ¼ 1), trials (RCT), four as cohort studies, and lyses, (i) 10 studies in terms of mean gain
and soft tissue augmentation in combination 11 as controlled clinical trials (CCT). More in width of keratinized tissue, (ii) two
with implant placement (n ¼ 1). than 585 patients were treated for augmen- studies in terms of shrinkage of keratinized
tation of keratinized soft tissue or attached tissue, and (iii) 10 studies in terms of the
Included studies gingiva. The methods and techniques used final width of attached gingiva.
The 28 studies that met the inclusion cri- for augmentation of keratinized tissue in-
teria are presented in Tables 3 and 4. Table 3 cluded: no treatment or scaling and root Mean gain in width of keratinized tissue
shows the data for studies regarding ‘kerati- planing, vestibuloplasty, APF in various (Table 5; Fig. 3). A total of 12 studies
nized tissue’ (part 1; 25 studies). Table 4 forms and designs, apically positioned (seven RCTs, three CCTs, and two cohort

Table 2. Excluded studies 2000; McGuire & Nunn 2005;Table 6; Fig.

Author Year Reason for exclusion 4). The WMD with 95% CI between the
Obwegeser 1967 Description of technique allogenic groups (APF/V plus ADMG or HF-
Möller & Jölst 1972 Only descriptive histology DDS) and the control groups (APF/V plus
Dreeskamp et al. 1973 No reported data on keratinized tissue FGG) was 28.41% (23.56, 33.26). The mean
Dordick et al. 1976b No reported data on width of keratinized tissue
shrinkage was statistically significantly
Flores de Jacoby 1976 No control group
et al. greater in the allogenic groups (P ¼ 0). The
Rozencweig 1976 Insufficient follow-up data; follow-up of 2 months only I-squared value of 95.1% indicated a signifi-
Yukna et al. 1977 Insufficient number of patients (4) cant heterogeneity between the two studies
Ackermann et al. 1980 Fully edentulous patients
Bachmann & 1980 No control group
(P ¼ 0).
Bernimoulin
Haase et al. 1980 Retrospective study Width of attached gingiva (Table 7; Fig.
Krekeler et al. 1980 No control group 5). Fifteen studies reported data on the
Löst 1980 No data on keratinized tissue
Ouhayoun et al. 1983 No measurements for control group; only descriptive width of the attached gingiva including
histology six RCTs, eight CCTs, and one cohort
Härle 1987 No data on keratinized tissue study (Table 7). Based on five studies, the
Schramm-Scherer & 1987 No reported outcomes on the width of keratinized tissue
width of the attached gingiva postopera-
Linder
Sbordone et al. 1988 Root coverage procedure tively was statistically significantly greater
Mercier et al. 1992 No control group; no data on keratinized tissue when APF/V plus autogenous tissue groups
Raghoebar et al. 1995 Only descriptive histology were compared with control groups (no
Lauer et al. 1996 Simultaneously with implant placement
treatment) (P ¼ 0) (Fig. 5A). The WMD
Shulman 1996 Follow-up of only 6 weeks; no control group
Al-Mahdy 1997 No control group with a 95% CI was 3.94 mm (3.64, 4.23).
Al-Belasy The I-squared value of 98.4% indicated a
Fröschl & 1997 Fully edentulous patients significant heterogeneity between the stu-
Kerscher
dies (P ¼ 0). The comparison between APF/
Carnio & Miller 1999 No control group
Lauer & Schimming 2001 No control group; only descriptive data V with or without the addition of autoge-
Wei et al. 2002 Only descriptive histology nous tissue revealed a statistically signifi-
Orsini et al. 2004 No measurements for the control group cant WMD of 0.83 mm (0.42, 1.25) in
Sezer et al. 2004 Fully edentulous patients
de Almeida et al. 2005 No reported treatment outcomes on width of keratinized
favor of the groups using autogenous tissue
tissue, volume or patient-centered outcomes (P ¼ 0.01) (Fig. 5B). Again, the I-squared
Luczyszyn et al. 2005 Control group does not use soft tissue augmentation value of 78.4% revealed significant hetero-
Griffin et al. 2006 No data on keratinized tissue geneity between the two studies (P ¼ 0.01).
Wessel & Tatakis 2008 No reported outcomes on width of keratinized tissue
The addition of an allogenic graft (ADMG)
to an APF/V resulted in a minor gain of
0.7 mm ( 0.1, 1.5) compared with the
studies) could be compared for mean gain (0.7 mm; 0.14, 1.54) (Fig. 3C). A border- APF/V alone (Fig. 5C). The comparison
in keratinized tissue using meta-analyses line statistical difference was observed be- between an APF/V with either an FGG or
(Table 5). The use of an APF/V plus auto- tween the two treatment modalities a BCT revealed a statistically significant
genous tissue resulted in a statistically (P ¼ 0.052). The mean difference between difference of 1.52 mm (1.73, 1.31) in favor
significant weighted mean difference an APF/V with either an allogenic graft or an of the group using the autogenous FGG
(WMD) of 4.49 mm (4.28, 4.71) compared autogenous graft was 0.85 mm ( 1.71, (P ¼ 0) (Fig. 5D). One study comparing an
with no treatment (P ¼ 0) (Fig. 3A). The I- 0.01) (Fig. 3D). Despite showing a high APF/V plus FDS with or without fenestra-
square value of 96.6% indicated a statisti- standard deviation, this mean gain in kera- tion of the flap demonstrated a statistically
cally significant heterogeneity between the tinized tissue was statistically significantly significant WMD of 1.17 mm (0.61, 1.73)
four studies (P ¼ 0). Based on one study different in favor of the groups using auto- in favor of the group using a fenestration of
reporting on the outcomes of two different genous tissue (P ¼ 0). The I-squared value the flap (P ¼ 0; Fig. 5E).
APF/V plus SCTG techniques, there was a indicated significant heterogeneity between
statistically non-significant WMD of the different studies (94.6%; P ¼ 0). Fenes- Percent shrinkage of attached gingiva. One
0.34 mm ( 0.45, 1.13) favoring method 1 tration of the flap when using an FDS CCT reported on the shrinkage of the
(a partial-thickness flap is raised and the statistically significantly improved the gain attached gingiva using two different treat-
SCTG is taken from below the palatal in keratinized tissue (1.22 mm; 0.71, 1.73; ment modalities (Schoo & Coppes 1976).
surface) over method 2 (the SCTG is ob- P ¼ 0) (Fig. 3E). The shrinkage of the attached gingiva was
tained by the thinning of a full-thickness statistically significantly greater for an
palatal flap) (P ¼ 0.401; Fig. 3B). The use of Percent shrinkage of keratinized tissue APF/V in combination with lyophilized
an APF/V plus an allogenic graft (ADMG) (Table 6; Fig. 4). Two RCTs reporting on dura mater (mean ¼ 63.1%; SD ¼ 9.3)
was slightly more favorable in terms of gain percent shrinkage of keratinized tissue were compared with an APF/V with an FGG
in keratinized tissue than an APF/V alone compared using a meta-analysis (Wei et al. (20.7%; SD 11.1) (Schoo & Coppes 1976).

Table 3. Included studies part 1: augmentation of keratinized tissue
Author Year of Study Test treatment Control 1 Control 2 Control 3 Follow-up Total Total Number Number of Number Number
publication design treatment treatment treatment period number of number of of sites sites control 1 of sites of sites
(weeks) patients sites test group group control control
2 group 3 group
Diedrich et al. 1972 CCT Vestibuloplasty Vestibuloplasty 17 15 30 15 15
with releasing
incision
Richter et al. 1973 CCT Vestibuloplasty Vestibuloplasty 35 12 24 12 12

without suturing
Edel 1974 Cohort APF plus SCTG APF plus SCTG APF plus 26 8 14 6 6 2
Study (method 1) (method 2) SCTG
(method
3)
Fagan & 1974 CCT APF plus FGG APF 12 10 22 10 12
Freeman
Matthiessen 1974 CCT Vestibuloplasty Vestibuloplasty 17 10 20 10 10
& Diedrich extended into
horizontal part
of ridge
Fagan 1975 CCT APF plus FGG APF 12 5 10 5 5
Dordick et al. 1976a RCT APF with APF plus FGG 26 60 30 30
releasing incision
plus FGG
Lange & 1976 CCT Vestibuloplasty Vestibuloplasty 208 8 16 8 8
Flores de with releasing
Jacoby incision
Schoo & 1976 Cohort APF plus lyoph. APF plus FGG 104 58 84 16 68
Coppes Study dura mater
James & 1978 CCT Vestibuloplasty/ Vestibuloplasty/ 12 14 28 14 14
McFall APF with APF plus FGG
releasing incision
plus FGG
de Trey & 1980 CCT APF plus FGG No treatment 14 12 24 12 12
Bernimoulin
151 |
Dorfman 1980 RCT APF plus FGG No treatment 104 92 184 92 92
et al.
Gher et al. 1980 Cohort Vestibuloplasty/ Vestibuloplasty/ 12 31 148 76 72
Study APF plus FDS APF plus FDS
with without
fenestration fenestration
Hangorsky & 1980 CCT Vestibuloplasty/ No treatment 52–416 34 80 40 40
Bissada APF plus FGG
Lange et al. 1981 CCT Vestibuloplasty Vestibuloplasty 26 15 30 15 15
according to according to
Schmid & Plagmann
Mörmann
Mörmann 1981 CCT APF plus FGG APF plus FGG APF plus APF plus 52 34 89 19 11 29 30
et al. (scalpel) (mucotom very FGG FGG
thin) (mucotom (mucotom
thin) inter-
mediate)
Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146–165

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;
Percent shrinkage of graft/grafted area. Se-
Number
3 group
control
of sites ven CCTs, one RCT, and one cohort study
reported on the shrinkage of the graft/
grafted area (Richter et al. 1973; Matthies-
sen & Diedrich 1974; James & McFall
Number
2 group
1978; Lange et al. 1981; Mörmann et al.

control
sites control 1 of sites
1981; Marxer et al. 1982; Pöllmann &
11
15
Scherer 1983). No statistically significant
differences were observed between most of
Number of
the various treatment modalities (different

group
techniques for vestibuloplasty). A border-

9
6
21
9
40
32
15
22
25
line significance was observed in favor of
an FGG placed on the periosteum (36.67%)
test group
instead of directly on the bone (23.25%)

Number
of sites
FDS, freeze-dried skin allograft; HF-DDS, human fibroblast-derived dermal substitute; TEMG, tissue-engineered mucosal graft; BCT, bilayered cell therapy.
(James & McFall 1978). In one study,
FGGs were placed at sites with o1 mm
6
9
21
40
25
32
15
22
25
of attached gingiva (Mörmann et al.
number of
1981). The FGGs were retrieved using

either a mucotom or a blade and with
Total
sites
42
80
45
64
12
45
44
18
50 various thicknesses ranging from 0.37 to

0.92 mm. The group with the thickest
number of
mean FGG retrieved showed statistically

patients
significantly less shrinkage (30%) than

Total
grafts with a mean thickness of 0.37 mm

9
21
16
45
32
12
45
22
25
(45% shrinkage) and 0.56 mm (44%).

Control 2 Control 3 Follow-up
(weeks)
208
312
52
26
26
13
52
13
26
treatment treatment period
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 (vestibu-
loplasty according to Plagmann 1979 (per-
plasty/APF
plasty/APF
Vestibuloplasty/ Vestibuloplasty Vestibulo-
Vestibuloplasty/ Vestibuloplasty/ Vestibulo-
plus SCTG
plus FGG
sonal communication); 297 mm2) com-

pared with the test group (vestibuloplasty
according to Schmid & Mörmann 1976;
Edlan & Mejchar
Scaling and root
Vestibuloplasty/ Scaling and root
Vestibuloplasty/ Vestibuloplasty/
Vestibuloplasty/ Vestibuloplasty
236 mm2) (Lange et al. 1981).

APF plus ADMG APF plus FGG
APF plus ADMG APF plus FGG
APF plus HF-DDS APF plus FGG
APF plus FGG

according to
treatment
Control 1
Depth of vestibulum. Two CCTs reported

planing
planing
data for the depth of the vestibulum follow-

APF plus TEMG APF
ing different vestibuloplasty procedures

lyophylised dura
(Lange et al. 1981; Marxer et al. 1982).

Test treatment
APF plus FGG
APF plus FGG
APF plus FGG
APF plus BCT
No statistically significant differences were

observed between an APF in combination
APF plus
mater
with an FGG (mean 3.9 mm; SD 1.1)

compared with an Edlan–Mejchar flap
(3.9 mm; SD 1.1) for the treatment of an
inadequate width of attached gingiva
Cohort
publication design
Study
Study
RCT
RCT
RCT
RCT
RCT
RCT
RCT
RCT
(Marxer et al. 1982). Slightly more gain in

vestibular depth was found using the
Schmid & Mörmann 1976 procedure
Year of
(12.5%) than with the Plagmann 1979

1982
Marxer et al. 1982
1983
1985
2000
2001
2005
Mohammadi 2007
2008
Table 3. Continued.
procedure (12.2%) (Lange et al. 1981).

Pöllmann &
McGuire &
Wei et al.
Patient-reported outcomes and esthe-

Dorfman
Kennedy
McGuire
Scherer
Author
tics. Two studies (one CCT, one RCT)

Harris
Nunn
et al.
et al.
et al.
et al.
reported on postoperative pain (Dordick

et al. 1976a; Harris 2001). In one study,

Table 4. Included studies part 2: augmentation of soft tissue volume
Author Year of Study Test Control Control Follow-up Total Total Number Number Number
publication design treatment 1 treatment 2 treatment period number number of patients of patients of patients
(weeks) of patients of sites test group control control 2
1 group 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 Study Total Total Number Number Number of Number Number of Number Follow-up Test Control 1 Control 2
publication design number number of of sites patients of sites patients of sites period treatment treatment treatment
of of sites patients test control 1 control 1 control 2 control 2 (weeks)
patients test
Diedrich 1972 CCT 15 30 15 15 15 15 17 Vestibuloplasty withVestibuloplasty
et al. releasing incision
Edel 1974 Cohort 8 14 6 6 2 26 APF plus SCTG APF plus SCTG APF plus SCTG
study (method 1) (method 2) (method 3)
Dorfman 1980 RCT 92 184 92 92 92 92 104 APF plus FGG No treatment
et al.
Gher et al. 1980 Cohort 31 148 76 72 8 Vestibuloplasty/APF Vestibuloplasty/APF
study plus FDS with plus FDS without
fenestration fenestration
Hangorsky 1980 CCT 34 40 34 40 34 40 52–416 Vestibuloplasty/APF No treatment
& Bissada plus FGG
153 |
Lange 1981 CCT 15 30 15 15 15 15 26 Vestibuloplasty Vestibuloplasty
et al. according to Schmidaccording to
& Mörmann Plagmann
Dorfman 1982 RCT 21 42 21 21 21 21 208 APF plus FGG Scaling and root
et al. planing
Kennedy 1985 RCT 32 64 32 32 32 32 312 Vestibuloplasty/APF Scaling and root
et al. plus FGG planing
Harris 2001 RCT 45 45 15 15 15 15 15 15 13 Vestibuloplasty/APF Vestibuloplasty/APF Vestibuloplasty/
plus ADMG plus FGG APF plus SCTG
McGuire & 2005 RCT 22 44 22 22 22 22 52 Vestibuloplasty/APF Vestibuloplasty/APF
Nunn plus HF-DDS plus FGG
Moham- 2007 RCT 9 18 9 9 9 9 13 Vestibuloplasty/APF Vestibuloplasty/APF
madi et al. plus TEMG
McGuire 2008 RCT 25 50 25 25 25 25 26 Vestibuloplasty/APF Vestibuloplasty/APF
et al. plus BCT plus FGG
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 ¼ bilayered cell therapy.

Table 5. Continued.
154 |
Author Treatment indication Outcome measure Baseline SD Postsurgery SD Change Change Baseline SD Postsurgery SD Change Change
test test test test SD control 1 control 1 control 1 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 (mm) 1.33 0.24 4.42 0.67 1.58 0.34 4.08 0.73
keratinized tissue
Dorfman et al. Inadequate width of Keratinized tissue (mm) 1.62 0.09 6.24 0.19 1.59 0.07 1.66 0.1
attached gingiva
Gher et al. Inadequate width of Keratinized tissue (mm) 2.13 1.2 6.3 1.67 1.76 1.27 5.08 1.49
keratinized tissue
Hangorsky & Inadequate width of Keratinized tissue (mm) 4.9 1.67 2.91 1.51
Bissada keratinized tissue
Lange et al. Vestibuloplasty Keratinized tissue (mm) 23.6 26.7
Dorfman et al. Inadequate width of Keratinized tissue (mm) 1.5 0.11 6.5 0.22 1.5 0.09 1.6 0.08
attached gingiva
Kennedy et al. Inadequate width of AG Keratinized tissue (mm) 1.3 0.1 6.2 0.1 1.4 0.1 1.6 0.1
Harris Inadequate width of 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
keratinized tissue

McGuire & Nunn Lack of keratinized Keratinized tissue (mm) 1.46 0.91 2.72 0.45 1.34 0.97 3.91 0.45
gingiva
Mohammadi Inadequate width of Keratinized tissue (mm) 1.3 0.4 4.1 1 1.5 0.4 3.4 0.8
et al. keratinized tissue
McGuire et al. Inadequate width of 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
keratinized tissue
Author Baseline SD Postsurgery SD Change Effect of device Effect of device Effect of control 1 Comments
control 2 control 2 control 2 vs. control 1 vs. control 2 vs. control 2
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 Statistics postoperative
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 Statistics postoperative
Mohammadi et al. Significant Statistics postoperative
McGuire et al. Significant negative


a

b
155 |
e
–4 –2 0 2 4
favors control group favors test/active group
Fig. 3. (A–E). Meta-analyses of mean gain in the width of keratinized tissue. Mean difference (mm) for test minus control. A: I-squared (percentage variation attributable to heterogeneity) ¼ 96.6%; test for overall effect:
z ¼ 41.37, P ¼ 0. B: significance test: z ¼ 0.84, P ¼ 0.401. C: significance test: z ¼ 1.64, P ¼ 0.101. D: I-squared ¼ 94.6%; test for overall effect: z ¼ 1.95, P ¼ 0.052. E: significance test: z ¼ 4.69, P ¼ 0. APF, apically positioned
flap; CI, confidence interval.

patients were treated for an inadequate Treatment outcomes (Table 8)

In the first case series, 21 patients with 26
control device vs.
Significant
Significant
width of gingiva. Perception of pain was
control localized alveolar defects were treated
Effect
measured based on the utilization of

either with an SCTG or hydroxylapatite
analgesic postoperatively. Patients felt
implants. The authors reported that 14 of
slightly more comfortable when the FGG
14 sites (SCTG) showed some shrinkage
8.9
was placed on the periosteum instead of
SD
12
within the first 4–6 weeks, but that the

placing it directly on bone. The differ-
RCT, randomized-controlled clinical trial; ADMG, acellular dermal matrix graft; HF-DDS, human fibroblast-derived dermal substitute; FGG, free gingival graft; SD, standard deviation.
control
augmented sites remained stable for 3

ences between the groups were not statis-
come test come
Out- SD Out-
years. In 10 of 12 sites treated with hydro-

21.8
tically significant (Dordick et al. 1976a).

16
xylapatite implants, no shrinkage was ob-

In the second study, three treatment
8.9
served. It was not mentioned how the

10
modalities were compared for augmen-

measurements were performed (Allen et
tation of keratinized tissue: (i) an ADMG,
test
45.5
al. 1985). In the second case series, loca-

71
(ii) an SCTG, and (iii) an FGG. No differ-

lized alveolar defects in eight patients with
ences in pain perception were observed
shrinkage of
shrinkage of
keratinized
keratinized
Percentage
Percentage
18 sites were treated with ADMG. A gain

Control Treatment Outcome
tissue (%)
tissue (%)
indication measure
between patients treated with ADMG

in the vertical ridge width of 0.61 mm (SD
and FGG; however, more pain was re-
0.77) and in the horizontal ridge width of
ported for SCTG-treated patients com-
1.72 mm (SD 0.59) was observed over 6
pared with ADMG-treated patients
Keratinized
keratinized
months. The shrinkage of the horizontal

gingival
(Harris 2001).
o1 mm
gingiva
Lack of
ridge width was 41.4% over the same

No significant differences were observed
period (Batista et al. 2001). In a cohort
with respect to postoperative bleeding in an
study, localized alveolar ridge defects were
RCT comparing a tissue-engineered skin
treat-
ment
treated with either an FGG or an SCTG.

FGG
FGG
product (BCT) with an FGG (McGuire

Patients were followed for 3.5 months. The
et al. 2008). However, there appears to be
HF-DDS
ADMG
treat-
augmented sites revealed a volume gain

control period ment
a difference depending on whether an FGG

Number Follow- Test
between 159 mm3 (SCTG; SD ¼ 80) and

is placed directly on bone (less bleeding, less
104 mm3 (FGG; SD ¼ 31). The differences
(weeks)
swelling) or on the periosteum for post-

between the two treatment modalities
operative hemostasis and swelling (Dordick
design number of number of patients of sites of patients of sites up
26
52
were statistically significant in favor of

et al. 1976a).
the SCTG group. The untreated defects
The overall patient morbidity (pain,
showed a slight increase in volume of
swelling, and bleeding) was evaluated in
6
22
6 mm3 (SD ¼ 5.4), which was statistically

another RCT revealing no differences be-
significantly different compared with the
tween the two treatment modalities (HF-
Number Number
two test groups using autogenous tissue

control
DDS vs. FGG; McGuire & Nunn 2005).

Table 6. Characteristics of included studies: shrinkage of keratinized tissue
(Studer et al. 2000).

However, subjects’ treatment preference
6
22
was significantly greater in the allograft

group (BCT) compared with the control
Discussion
test
group (FGG) in a recently published study

6
22
(McGuire et al. 2008). In addition, a better

The present systematic review focused on
color and texture match to the surround-
Number
answering the question of whether one

ing tissue was reported for the allograft
of sites test
method is superior over others for soft

6
22
groups (HF-DDS; BCT) compared with

tissue augmentation techniques. In terms
control sites (FGG) in two recent studies
of increasing the width of keratinized tis-
Total
(McGuire & Nunn 2005; McGuire et al.

sue, 25 studies met the inclusion criteria.
12
44
2008).
Out of these, 14 could be compared using
meta-analyses. In terms of soft tissue vo-
patients
Part 2: augmentation of soft tissue volume

lume augmentation, only three studies met
Author Year of Study Total
Three studies met the inclusion criteria as

the inclusion criteria. No meta-analysis
12
22
they reported on soft tissue volume aug-

could be performed due to heterogeneity
mentation (Allen et al. 1985; Studer et al.
between the studies.
RCT
RCT
2000; Batista et al. 2001). Two studies

were designed as cohort studies (Allen
cation
publi-
et al. 1985; Studer et al. 2000), and one Part 1: augmentation of keratinized tissue/
2000
McGuire 2005
attached gingiva
as a case series (Batista et al. 2001). No
& Nunn
meta-analysis could be performed due to Mean gain in the width of keratinized tissue
et al.
Wei
heterogeneity in the study design and treat- The present review demonstrated the
ment modalities. superiority of APF/V plus autogenous

mean

author year_of_publication graft_1 control_1 difference (95% CI)
Wei et al. 2000 ADMG FGG 55.00 (42.50, 67.50)
McGuire & Nunn 2005 HF-DDS FGG 23.70 (18.44, 28.96)
Overall (I-squared = 95.1%, p = 0.000) 28.41 (23.56, 33.26)
157 |
–10 0 20 40 60 80 100
favors test/active group favors control group
Fig. 4. Meta-analysis of percentage shrinkage of keratinized tissue. Mean difference (%) for test minus control. I-squared (percentage variation attributable to heterogeneity) ¼ 95.1%; test for overall effect: z ¼ 11.49, P ¼ 0. CI,
confidence interval; ADMG, acellular dermal matrix allograft; FGG, free gingival graft; HF-DDS, human fibroblast-derived dermal substitute.

158 |
Table 7. Characteristics of included studies: width of attached gingiva
Author Year of Study Total Total Number of Number Number of Number Follow-up Test Control Treatment Outcome
publi- design number of number patients of sites patients of sites period treatment treatment indication measure
cation patients of sites test test control control (weeks)
Diedrich et al. 1972 CCT 15 30 15 15 15 15 17 Vestibuloplasty Vestibuloplasty Vestibuloplasty Width of attached
with releasing gingiva (mm)
incision
Richter et al. 1973 CCT 12 24 12 12 12 12 35 Vestibuloplasty Vestibuloplasty Vestibuloplasty Width of attached

without suturing gingiva (mm)

Fagan & 1974 CCT 10 22 10 10 10 12 12 APF plus FGG APF Inadequate width Width of attached
Freeman of attached gingiva gingiva (mm)
Matthiessen 1974 CCT 10 20 10 10 10 10 17 Vestibuloplasty Vestibuloplasty Vestibuloplasty Width of attached
& Diedrich extended into gingiva (mm)
horizontal part of
ridge
Fagan 1975 CCT 5 10 5 5 5 5 12 APF plus FGG APF Inadequate width Width of attached
of attached gingiva gingiva (mm)
Fagan 1975 CCT 5 10 5 5 5 5 12 APF plus FGG APF No attached Width of attached
gingiva gingiva (mm)
Lange & 1976 CCT 8 16 8 8 8 8 208 Vestibuloplasty Vestibuloplasty Vestibuloplasty Width of attached
Flores de with releasing gingiva (mm)
Jacoby incision
de Trey & 1980 CCT 12 24 12 12 12 12 14 APF plus FGG No treatment Attached Width of attached
Bernimoulin gingivao1 mm gingiva (mm)
Dorfman et 1980 RCT 92 184 92 92 92 92 104 APF plus FGG no treatment Inadequate width Width of attached
al. of attached gingiva gingiva (mm)
Gher et al. 1980 Cohort 31 148 76 72 8 Vestibuloplasty/APF Vestibuloplasty/APF Inadequate width Width of attached
study plus FDS with plus FDS without of keratinized gingiva (mm)
fenestration fenestration tissue
Hangorsky & 1980 CCT 34 40 34 40 34 40 52–416 Vestibuloplasty/APF No treatment Inadequate width Width of attached
Bissada plus FGG of keratinized gingiva (mm)
tissue
Dorfman 1982 RCT 21 42 21 21 21 21 208 APF plus FGG Scaling and root Inadequate width Width of attached
et al. planing of attached gingiva gingiva (mm)
Kennedy 1985 RCT 32 64 32 32 32 32 312 Vestibuloplasty/APF Scaling and root Inadequate width Width of attached
et al. plus FGG planing of attached gingiva gingiva (mm)

Wei et al. 2000 RCT 12 12 6 6 6 26 APF plus ADMG APF plus FGG Attached Width of attached
gingivao1 mm gingiva (mm)
Mohammadi 2007 RCT 9 18 9 9 9 9 13 Vestibuloplasty/APF Vestibuloplasty/APF Inadequate width Width of attached
et al. plus TEMG of keratinized gingiva (mm)
tissue
McGuire 2008 RCT 25 50 25 25 25 25 26 Vestibuloplasty/APF Vestibuloplasty/APF Inadequate width Width of attached
et al. plus BCT plus FGG of keratinized gingiva (mm)
tissue
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.

postoperatively
postoperatively
postoperatively
tissue. This information is derived from
Comments
studies comparing APF/V plus autogenous
Statistics
Statistics
Statistics
tissue vs. scaling and root planing and vs.
untreated controls. The overall WMD was
statistically significant, despite showing
device vs.
large heterogeneity between the studies.

control 2
Effect of
It would be interesting to see what the

effect of autogenous tissue in this treat-
ment concept is. However, this outcome
device vs.
Significant
Significant
Significant
Significant
Significant
Significant
Significant
Significant
Significant
Significant
control 1
significant
could not be evaluated due to a lack of

Effect of
further control groups or other studies.

Not
There is a need for studies evaluating

the effect of autogenous tissue, especially
control SD
because this treatment concept is asso-

Change
ciated with higher morbidity due to the

0.26
0.46
0.34
0.44
0.37
second surgical site (Wessel & Tatakis
2008).
Change
control
To overcome issues associated with

higher morbidity when autogenous tissue
3.33
2.87
5.57
2.37
3.1
3.4
2.6
is used, allogenic grafts have been intro-

duced in mucogingival surgery. Allogenic
0.24
0.34
0.11
0.07
1.67
1.42
0.07
0.49
0.37
SD
0.3
0.1
0.7
grafts have been tested in combination

with APF/V. The results of one included
Postsurgery
study demonstrated only a borderline sta-

control
tistical significance compared with APF/V

3.49
4.13
2.87
0.38
0.36
4.01
1.71
6.15
2.62
0.3
3.8
3.5
0.5
2.3
alone (Mohammadi et al. 2007).

5
Based on the results of this review, the

0.14
0.25
0.14
0.05
0.97
0.07
0.41
0.14
direct comparison of APF/V plus either

SD
0.1
0.4
autogenous or allogenic tissue revealed a

statistically significant difference favoring
Baseline
control
the use of autogenous tissue. Interestingly,

0.74
0.33
0.71
0.57
0.24
0.4
0.8
0.3
1.6
1.2
1.6
0.3
0.3
differences between the various allogenic

0
grafts were observed. One study compared

Change
test SD
an APF/V procedure with the addition of an

0.25
0.38
0.25
0.92
0.37
ADMG, an FGG, or an SCTG (Harris

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

compared with the SCTG. On the other
test
4.37
4.06
2.59
0.85
4.2
3.7
2.8
hand, the tissue-engineered grafts (HF-

DDS, BCT) demonstrated statistically sig-
0.26
0.41
0.25
0.27
0.21
1.82
1.79
0.23
0.89
0.38
SD
0.1
nificantly less gain in keratinized tissue

than the respective control groups (autoge-
Postsurgery
nous tissue). Overall, an APF/V plus an

ADMG appears to be more effective than
test
4.31
4.13
3.67
4.71
5.18
3.53
3.25
4.9
4.3
5.2
4.5
4.8
1.1
the tissue-engineered grafts (BCT, HF-

4
DDS) in comparison with autogenous tis-

0.05
0.08
0.02
0.08
0.07
0.98
0.06
0.26
0.14
sue. However, one might speculate that

SD
0.1
0.4
these observations are due to the fact that

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

test
0.11
0.13
0.46
0.35
0.91
0.68
0.26
1.3
1.5
1.6
0.1
0.3
0.3
0.2
in the other two studies, where the width

Table 7. Continued.
of the grafts for control and test sites was

Mohammadi et al.
Lange & Flores de
held constant (5 mm) (McGuire & Nunn

Fagan & Freeman
Dorfman et al.
Dorfman et al.
Matthiessen &
McGuire et al.
Diedrich et al.
2005; McGuire et al. 2008). Unfortu-

Kennedy et al
Richter et al.
Hangorsky &
Bernimoulin
Gher et al.
nately, the first study does not provide

Wei et al.
de Trey &
Diedrich
Author
Bissada
Jacoby
Fagan
Fagan
information on the width of the graft that

was transplanted (Harris 2001).

160 |
a
b

c

–2 0 2 4
favours control group favours test/active group
Fig. 5. (A–E). Meta-analyses of the width of attached gingiva at the end of the study. Mean difference (mm) for test minus control. A: I-squared (percentage variation attributable to heterogeneity) ¼ 98.4%; test for overall effect:
z ¼ 25.83, P ¼ 0. B: I-squared ¼ 78.4%; test for overall effect: z ¼ 3.91, P ¼ 0. C: significance test: z ¼ 1.72, P ¼ 0.085. D: significance test: z ¼ 14.33, P ¼ 0. E: significance test: z ¼ 4.08, P ¼ 0.CI, confidence interval; APF,
apically positioned flap.

Percent shrinkage of keratinized tissue
Not mentioned how

measurements were
The meta-analysis revealed statistically
Gain in vertical
volume (mm3)
% shrinkage
ridge height
(descriptive)
significant less shrinkage for the autoge-
ridge width
Comments
Outcome
horizontal
horizontal
Soft tissue
Shrinkage
measure
performed
nous control groups (FGG; Table 5; Fig. 3).
Gain in
(mm)
(mm)
The reason for the large shrinkage of
ADMG compared with autogenous tissue
may be due to its fabrication process.
alveolar ridge
alveolar ridge
alveolar ridge
alveolar ridge
alveolar ridge
ADMG is processed from cadaver skin
of defect
Localized
Localized
Localized
Localized
Localized
control 1 vs.
and the epidermis and cellular material
defect
defect
defect
defect
defect
Significant
Type
control 2
Effect of
are removed. Histologic observations of
ADMG placed to increase the width of
Untreated
Control
2 treat-
keratinized tissue showed tissue that sub-

defect
ment
stantially differed from any oral mucosa

(Wei et al. 2002). The connective tissue
Significant
control 2
Effect of
Hydroxyl-
test vs.
Control
1 treat-
portion of the ADMG contained dense

apatite
ment
collagen fibers with scattered elastic fibers.

FGG
SCTG, subepithelial connective tissue graft; ADMG, acellular dermal matrix graft; FGG, free gingival graft; NA, not applicable; SD, standard deviation. The epithelial layer covering the connec-
ADMG
ADMG
ADMG
treat-
ment
tive tissue showed heterogenous expression

SCTG
SCTG
Test
Significant
control 1
Effect of
test vs. of keratinization and a flat epithelium–
connective tissue interface. The epithe-
Follow-up
NA
NA
NA
NA
(weeks)
lium was mostly para- or orthokeratinized

period
toward the gingiva and non-keratinized to

24
14
27
27
27
the alveolar mucosa. The authors sug-

control 2
Number
gested that due to the non-vital matrix of

of sites
the ADMG, the epithelium–connective

test
SD
5.4
14
12
18
18
18
tissue of the surrounding recipient site

Number
patients
directed the epithelium differentiation of

the ADMG (Wei et al. 2002). These find-
test
Outcome
control 2
of
12
ings may predominantly explain the high

control 2
shrinkage of this allogenic dermal matrix.

Number
of sites
On the other hand, the HF-DDS is ob-

tained from neonatal fibroblasts on a poly-
6
control 1
glyactin mesh. The included cells can

control 2
Number
patients
multiply and produce collagen and growth

SD
31
factors, which can produce greater tissue.

of
The shrinkage reported for HF-DDS is still

control 1
Number
greater than for autogenous tissue, but the

of sites
Table 8. Characteristics of the included studies: soft tissue volume
10 of 12 sites:
no shrinkage
mean shrinkage values are lower in com-

Outcome
control 1
12
12
parison with studies using ADMG (Wei

control 1
et al. 2000; McGuire & Nunn 2005).

Number
patients
104
The inclusion of living cells (tissue engi-

of
12
neering) may therefore play a critical role as

the cells could enhance the results by
0.59
0.77
number
of sites
test
SD
80
stabilizing the allogenic tissue through the

Total
26
30
18
18
18
production of extracellular matrix mole-

cules, fibers, and growth factors.
patients
number
14 of 14 sites: shrinkage
within first 4–6 weeks,
then stable for 3 years
Total
of
21
30
Shrinkage of the graft/grafted area

No statistically significant differences were
design
Cohort
Cohort
Outcome
Study
observed in the various studies comparing

series
series
series
study
study
Case
Case
Case
1.72
0.61
41.4
different vestibuloplasty procedures. The

test
159
only difference observed was that more

Author Year of
cation
publi-
shrinkage of FGGs was observed when

1985
2000
2001
2001
2001
they were placed on the periosteum rather

Batista et al.
Batista et al.
Batista et al.
Studer et al.
Allen et al.
than on bone (James & McFall 1978). This

Batista
Batista
Batista
Studer
Author
Allen
et al.
et al.
et al.
et al.
et al.
observation from one single study is sur-

prising because the periosteum is known to

be a highly vascularized tissue and can using the ADMG (Mohammadi et al. between the two sites. Another explana-
provide blood supply within short distance 2007). The direct comparison between a tion is that the questionnaires were not
to grafts. The outcome is also in contrast to tissue-engineered product (BCT) and an administered to the patients until 3–12
an experimental study in rats, which FGG, both in combination with an APF/ months following the surgery. Important
showed the importance of the periosteum V, resulted in statistically significantly information of the postoperative outcome
for the healing of full-thickness skin de- more attached gingiva for the autogenous might have been missed.
fects (Koga et al. 2007). It was demon- group (FGG) (McGuire et al. 2008). Again,
strated that the thickness of the grafts no other control group (APF/V alone) was Part 2: augmentation of soft tissue volume
(FGG) had an influence on the shrinkage included. Therefore, the effect of the APF/ Three studies met the inclusion criteria for
(Mörmann et al. 1981). The thickest grafts V alone could not be calculated. augmentation of soft tissue volume. Out of
showed statistically significantly the least these, only one was designed as a compara-
shrinkage. Similar findings with an allo- Patient-reported outcomes and esthetics tive cohort study (Studer et al. 2000). The
genic graft (HF-DDS) regarding the rela- A recent publication evaluating patient greatest amount of soft tissue volume was
tionship thickness and shrinkage were outcomes following SCTG and FGG pro- observed for the SCTG group with signifi-
reported (McGuire & Nunn 2005). In cedures demonstrated that FGG is asso- cant differences from the control groups
that study, multiple-layer HF-DDS ciated with a greater incidence of donor (FGG, untreated sites). No comparative
showed significantly less shrinkage and site pain compared with SCTG at 3 days studies were found using allogenic grafts
greater keratinized tissue than monolayer (Wessel & Tatakis 2008). In the present instead of autogenous tissue for volumetric
HF-DDS. review, five included studies reported out- augmentation. The evidence for volu-
comes on the tolerance of the procedure, or metric soft tissue augmentation techniques
Width of attached gingiva the postoperative comfort of the patients. is therefore low. SCTGs can be recom-
The results of the present review indicate Patients felt slightly more comfortable, but mended for augmentation of localized al-
that the combination of APF/V plus auto- reported more bleeding and swelling when veolar defects. However, one has to bear in
genous tissue is a successful treatment the FGG was placed on the periosteum mind that these results are derived from
concept with a statistically significantly rather than directly on the bone (Dordick only one study including 30 patients with a
greater increase in attached gingiva com- et al. 1976a, 1976b). The major advantage follow-up of 14 weeks and a significant
pared with untreated control groups. The of using allogenic grafts instead of autoge- decrease in volume (graft shrinkage) be-
addition of autogenous tissue to an APF/V nous tissue is suggested to be the abandon- tween 4 and 14 weeks.
improved the outcome compared with an ment of a second surgical site. In a Several reasons may be responsible for
APF/V alone. Unfortunately, no studies prospective clinical study evaluating post- the low number of studies published in this
were identified comparing an APF/V with operative complications following gingival field: first, the currently investigated grafts
untreated control groups. Therefore, the augmentation procedures, the use of other than autogenous tissue are very thin
effect of the APF/V procedure can only be ADMG (instead of FGG or SCTG) signifi- due to the manufacturing process. Any
calculated indirectly. Based on a WMD cantly reduced the probability of swelling volume augmentation would likely require
between APF/V plus autogenous tissue and bleeding at the donor site (Griffin et al. larger amounts of tissue or a folding proce-
and an APF/V procedure of 0.83 mm 2006). The same treatment modalities dure would be necessary to gain greater
(0.42, 1.25), and a WMD between APF/V (ADMG, FGG, and SCTG) were compared volume. A folding process further hampers
plus autogenous tissue and untreated con- in one of the included studies (Harris vascularization of the graft and could in-
trols of 3.94 mm (3.64, 4.23), the effect of 2001). No differences in pain perception duce extensive shrinkage, which is cri-
the APF/V should be around 3 mm. The were observed between patients treated tical especially for acellular dermal grafts
greatest increase in the width of keratinized with ADMG or FGG, but more pain was (Batista et al. 2001; Wei et al. 2002).
tissue therefore derives from the APF/V reported by patients receiving SCTGs than Second, allogenic grafts including living
procedure. The effect of the autogenous ADMGs. No significant differences were cells might be a better alternative, because
tissue appears to be rather small, even observed with respect to postoperative these grafts tend to show less shrinkage
though statistically significant based on bleeding in a study comparing a tissue- than acellular dermal substitutes. On the
two included studies. When using an engineered graft (BCT) with an FGG; how- other hand, these grafts appear to build an
APF/V in combination with an FDS it ever, the patient’s treatment preference epithelial layer and the effect of a folding
was found that the fenestration of the flap was significantly greater in the allogenic procedure remains unclear. Options for
had a statistically significant influence on group (BCT; McGuire et al. 2008). The future grafts might include collagen-based
the outcome (Gher et al. 1980). The effect overall patient morbidity (pain, swelling, matrices, which have been evaluated in
of the FDS remains unclear as the cited and bleeding) was comparable when the preclinical and clinical studies in ridge
study did not have a control group without two treatment modalities HF-DDS and preservation techniques and are currently
the allogenic graft and no other studies FGG were evaluated (McGuire & Nunn under investigation for soft tissue volume
using FDS were included. Another study 2005). One reason for these observations augmentation (Jung et al. 2004; Heberer
using an APF/V procedure with or without might be the fact that patients were treated et al. 2008; Araujo et al. 2009). In contrast
the addition of an ADMG demonstrated a in a split-mouth design, which could make to grafts to increase the width of keratinized
borderline difference in favor of the group it difficult for the patients to differentiate tissue, collagen-based matrices intended to

be used for volume augmentation are not methodological in vitro study, several da- APF/V plus autogenous tissue. Indeed,
placed in sites with a lack of or a reduced tasets of three-dimensional objects were allogenic grafts (BCT, HF-DDS) resulted
vascular supply. The grafts are fully sur- captured and volumetric differences were in better color and texture match to sur-
rounded by soft tissue at the recipient site. measured. The tested optical three-dimen- rounding tissue compared with FGGs har-
Therefore, one might speculate that suita- sional system showed excellent accuracy vested from the palate. For soft tissue
ble grafts would not be dependent on and high reproducibility for measuring volume augmentation only limited data
enclosed living cells (tissue-engineered pro- volume differences between specimens are available. For localized alveolar defects
ducts). On the other hand, higher demands imitating alveolar ridge defects after aug- SCTGs provided greater volume gain than
are needed regarding the mechanical prop- mentation procedures (Windisch et al. full-thickness gingival grafts. However,
erties because shear and compression forces 2007). The same method has been used the evidence is rather weak, since only
are constantly applied to the grafts. Third, to measure dimensional changes of the one comparative cohort study has been
and possibly the most important reason is ridge contour in a preclinical study (Fickl published.
that there is currently no standardized reli- et al. 2009), and to document volumetric Research is needed to investigate the
able technique available for the measure- soft tissue changes of the interdental pa- current techniques and substitutes in
ment of soft tissue volume. In one of pilla (Strebel et al. 2009). Because this RCT including patient-reported outcome
the included studies, a time-consuming method is non-invasive, and has been measures and esthetics. Future studies
procedure based on cast measurements established in preclinical and clinical stu- should be conducted to provide long-term
was applied. For the measurements using dies, it might be applicable for the desired data within an observation period of at least
the so-called Moiré method, extensive measurements of soft tissue volume dif- 12 months. Non-invasive standardized
appliances are required (Studer et al. ferences. methods to characterize the tissue type
2000). These aspects influence and limit and to measure gain, loss, and changes of
the clinical applicability. In another study, grafted areas concerning extension, vo-
measurements were performed using a Conclusions lume, and esthetics have to be established
periodontal probe. These measurements and validated. Future research in soft tissue
may not reflect the changes of the entire The present systematic review revealed regeneration should be directed toward re-
augmented volume (Batista et al. 2001). that with respect to increasing the width duction of morbidity, increased reliability,
Recently, a new method has been de- of keratinized tissue or attached gingiva and elimination of autogenous tissue. Tis-
scribed to measure soft tissue volume around teeth, APF/V procedures are suc- sue engineering might be a possibility to
(Windisch et al. 2007). In operative den- cessful treatment concepts. The addition of improve current techniques and offer new
tistry, for example, an optical system is autogenous tissue statistically significantly options in this field.
available that allows one to capture infor- increases the width of attached gingiva.
mation about the shape of tooth prepara- Based on the included studies, the various Acknowledgement: This review has
tions and the adjacent soft tissue contours allogenic grafts in combination with APF/ been funded by the Clinic for Fixed and
(Mörmann & Brandestini 1996). With this V do not improve the outcome regarding Removable Prosthodontics and Dental
system a three-dimensional image is ob- the mean gain in the width of keratinized Material Science, University of Zurich.
tained after scanning the intraoral anat- tissue and the width of attached gingiva No conflict of interest is reported for
omy with a camera (Schneider 2003). In a postoperatively compared with the use of this article.
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A Systematic Review Assessing Soft Tissue Augmentation Techniques

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Daniel S.

Thoma A systematic review assessing soft

146 c 2009 John Wiley & Sons A/S

c 2009 John Wiley & Sons A/S

database, the abstract of the printed article keratinized cemento-enamel junction

did not provide sufficient information re-

meta-analysis on mean differences, the size first electronic search:

tify heterogeneity. The I-squared measure

(inter-reader agreement k ¼ 0.81 0.05).

c 2009 John Wiley & Sons A/S

Table 2. Excluded studies 2000; McGuire & Nunn 2005;Table 6; Fig.

c 2009 John Wiley & Sons A/S

Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146–165

1978; Lange et al. 1981; Mörmann et al.

1981; Marxer et al. 1982; Pöllmann &

the various treatment modalities (different

techniques for vestibuloplasty). A border-

instead of directly on the bone (23.25%)

1981). The FGGs were retrieved using

50 various thicknesses ranging from 0.37 to

mean FGG retrieved showed statistically

significantly less shrinkage (30%) than

grafts with a mean thickness of 0.37 mm

(45% shrinkage) and 0.56 mm (44%).

Vestibular area. One CCT evaluated the

Vestibuloplasty/ Vestibuloplasty/ Vestibulo-

sonal communication); 297 mm2) com-

Vestibuloplasty/ Scaling and root

236 mm2) (Lange et al. 1981).

APF plus ADMG APF plus FGG

APF plus HF-DDS APF plus FGG

APF plus FGG

Depth of vestibulum. Two CCTs reported

data for the depth of the vestibulum follow-

ing different vestibuloplasty procedures

(Lange et al. 1981; Marxer et al. 1982).

APF plus FGG

APF plus FGG

APF plus FGG

APF plus BCT

No statistically significant differences were

with an FGG (mean 3.9 mm; SD 1.1)

(Marxer et al. 1982). Slightly more gain in

(12.5%) than with the Plagmann 1979

Marxer et al. 1982

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

Patient-reported outcomes and esthe-

tics. Two studies (one CCT, one RCT)

reported on postoperative pain (Dordick

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Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146–165

c 2009 John Wiley & Sons A/S

Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146–165

patients were treated for an inadequate Treatment outcomes (Table 8)

measured based on the utilization of

within the first 4–6 weeks, but that the

augmented sites remained stable for 3

years. In 10 of 12 sites treated with hydro-