2009 A Systematic Review Assessing Soft Tissue

Daniel S. Thoma Goran I. Benic Marcel Zwahlen Christoph H. F. Ha mmerle Ronald E.
Jung
A systematic review assessing soft tissue augmentation techniques
Authors afliations: , Marcel Zwahlen, Daniel S. Thoma, Goran I. Benic Christoph H. F. Ha mmerle, Ronald E. Jung, Clinic for Fixed and Removable Prosthodontics and Dental Material Science, University of Zurich, Zurich, Switzerland M. Zwahlen, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland Correspondence to: Daniel S. Thoma Clinic for Fixed and Removable Prosthodontics and Dental Material Science University of Zurich Plattenstrasse 11 CH-8032 Zurich Switzerland Tel.: 41 44 634 32 57 Fax: 41 44 634 43 05 e-mail: daniel.thoma@zzmk.uzh.ch
Conicts of interest: The authors declare no conicts of interest.
Key words: allogenic dermal matrix, free gingival graft, human broblast-derived dermal substitute, keratinized tissue, soft tissue augmentation, soft tissue volume, subepithelial connective tissue graft, vestibuloplasty 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 one method superior 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 complemented by additional hand searching. Relevant studies were identied and statistical results were reported for meta-analyses including the test minus control weighted mean differences with 95% condence intervals, the I-squared statistic for tests of heterogeneity, and the number of signicant studies. Results: Twenty-ve (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 ap/ vestibuloplasty (APF/V) procedure resulted in a statistically signicantly greater gain in keratinized tissue than untreated controls. APF/V plus autogenous tissue revealed statistically signicantly more attached gingiva compared with untreated controls and a borderline statistical signicance compared with APF/V plus allogenic tissue. Statistically signicantly 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 signicantly 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 signicantly increases the width of attached gingiva. For soft tissue volume augmentation, only limited data are available favoring SCTGs over FGG.
Date: Accepted 20 May 2009

To cite this article: GI, Zwahlen M, Ha Thoma DS, Benic mmerle CHF, Jung RE. A systematic review assessing soft tissue augmentation techniques. Clin. Oral Impl. Res. 20 (Suppl. 4), 2009; 146165. doi: 10.1111/j.1600-0501.2009.01784.x
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
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Thoma et al Soft tissue grafting: a systematic review
et al. 1986; Artzi et al. 1993; Langer 1996). However, two recent reviews concluded that there is insufcient or even a lack of evidence regarding the inuence 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 to maintain periodontal health and to prevent gingival recession (Nabers 1966; Sullivan & Atkins 1969). It was also concluded that for the maintenance of gingival health 2 mm of keratinized gingiva is adequate (Lang & Lo e 1972). Because an adequate amount of keratinized tissue has not been dened yet, the decision to augment the width of keratinized gingiva around dental implants and teeth still depends on the clinicians choice and the planned surgical and prosthetic treatment. Historically, the methods to augment keratinized tissue included: (i) an apically positioned ap (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 preprosthetic 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). The 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 patients morbidity (Farnoush 1978; Grifn 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 patients sex and age, the quantity and quality of tissue that can be retrieved varies. The location of the palatal vessels and nerves further limits the total amount that is available for grafting procedures (Soileau & Brannon 2006). In order to overcome these issues with autogenous tissue, alternative techniques
and materials primarily of allogenic origin have been developed. Among the rst products introduced in mucogingival surgery were freeze-dried skin allografts, initially used as a replacement for FGGs in combination with an APF for the augmentation of keratinized tissue (Yukna & Sullivan 1978). Later in the 1980s, allogenic dermal substitutes like the acellular dermal matrix graft (ADMG; Allodermt, Life Cell Corporation, The Woodlands, TX, USA), originally developed for covering full-thickness burn wounds (Wainwright 1995), have been used to increase keratinized tissue, for a 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 broblast-derived dermal substitute s (HF-DDS, Dermagraft , Advanced Tissue Sciences Inc., La Jolla, CA, USA) and a s human skin equivalent (BCT, Apligraf , Organogenesis, Canton, MA, USA) include a cellular component. Both grafts have been investigated in clinical trials in comparison with 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 one method is superior 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).
lished 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 broblastderived 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 ve 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.
Part 2: augmentation of soft tissue volume
Material and methods

Search strategy
A Medline (PubMed) search was performed for human studies, including articles pub-
For studies focusing on soft tissue volume gain, any prospective case series with at least ve patients was included. The minimal follow-up time was 3 months. The reported treatment outcomes had to
Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146165
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include either clinical and/or histological measures of the soft tissue volume.
Exclusion criteria
Table 1. Abbreviations used in text, gures, and tables

ADMG APF APF/V BCT CCT CI FGG HA HF-DDS NA RCT SCTG SD TEMG WMD Acellular dermal matrix graft Apically positioned ap Apically positioned ap/vestibuloplasty Bilayered cell therapy Controlled clinical trial Condence interval Free gingival graft Hydroxylapatite bone substitute Human broblast-derived dermal substitute Not applicable Randomized-controlled clinical trial Subepithelial connective tissue graft Standard deviation Tissue-engineered mucosal graft Weighted mean differences
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 two authors (D.S.T., G.I.B.) based on the inclusion criteria. Disagreements were resolved by discussion. Cohens k coefcient was used as a measure of agreement between the two 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 the title and abstract did not provide sufcient 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 two readers. Disagreements were resolved by discussion.
Data extraction
margo gingivae
free gingiva / periodontal probing depth keratinized tissue attached gingiva cemento-enamel junction
muco-gingival junction
Fig. 1. Schematic drawing of the parameters analyzed at the dento-gingival unit.
Two reviewers independently extracted the data using data extraction tables. Any disagreements were resolved by discussion aiming for a consensus. For abbreviations used throughout the text, tables, and gures 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 in the test group, number of patients in the 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 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). Smoking status was only assessed in one study and therefore not indicated in the tables. Figure 1 represents a schematic drawing of the analyzed parameters.
number of sites control group(s), follow-up period, graft test group, graft control group(s), type of defect, and gain/change in volume.
Statistical analysis
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,
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 the width of keratinized tissue in mm from baseline to the end of the study (10 studies), (2) percentage shrinkage of width of keratinized tissue in mm from baseline to follow-up (two studies), and (3) mean width of attached gingiva at followup (10 studies). The outcome of interest was, for each study, the postintervention mean difference between the test and the control group. To be able to perform a
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meta-analysis on mean differences, the 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-specic mean differences and summary estimates obtained from the meta-analyses. We report 95% condence intervals (CI), Cochrans Q statistic, and the I-squared statistic to test for and quantify 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, a 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, USA).
first electronic search: 1471 titles
inter-reader agreement k = 0.82 0.02
independently selected by 2 reviewers and agreed by both: 115 titles abstracts obtained
inter-reader agreement k = 0.81 0.05
independently selected by 2 reviewers and agreed by both: 58 abstracts full text obtained
Results
keratinized tissue: 48 soft tissue volume: 4 review: 6
Study characteristics
The electronic search identied 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-ve full-text articles were obtained including seven studies found through hand searching. Finally, 25 (keratinized tissue) and three (soft tissue volume) articles met the inclusion criteria.
Exclusion of studies
further handsearching 7 articles (references of full text articles)
excluded: 1 excluded: 30 final number of studies included keratinized tissue: 25

Fig. 2. Search strategy.
final number of studies included soft tissue volume: 3
The reasons for excluding studies (n 31, Table 2) after the full text was obtained were: no reported or insufcient 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 insufcient number of patients (n 1), retrospective study (n 1), insufcient follow-up data (n 1), description of technique (n 1), root coverage procedure (n 1), retrospective study (n 1), and soft tissue augmentation in combination with implant placement (n 1).
Included studies
refers to clinical studies dealing with soft tissue volume (part 2; three studies).
Part 1: keratinized tissue Treatment outcomes
The 28 studies that met the inclusion criteria are presented in Tables 3 and 4. Table 3 shows the data for studies regarding keratinized tissue (part 1; 25 studies). Table 4
Patient-based treatment outcomes on augmentation of keratinized tissue retrieved from 25 included studies are presented in Tables 3 and 57. Ten studies were designed as randomized-controlled clinical trials (RCT), four as cohort studies, and 11 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 planing, vestibuloplasty, APF in various forms and designs, apically positioned
ap/vestibuloplasty (APF/V) in combination with autogenous tissue (FGG, SCTG), and APF/V in combination with allogenic grafts (ADMG, BCT, FDS, and HF-DDS). The mean follow-up period was 63 weeks (12416 weeks). The reason for treating the patients included a lack of or an inadequate width of attached gingiva/keratinized tissue (22 studies) or vestibuloplasty (three studies). In summary, 14 studies were eligible for comparison using meta-analyses, (i) 10 studies in terms of mean gain in width of keratinized tissue, (ii) two studies in terms of shrinkage of keratinized tissue, and (iii) 10 studies in terms of the nal width of attached gingiva. Mean gain in width of keratinized tissue (Table 5; Fig. 3). A total of 12 studies (seven RCTs, three CCTs, and two cohort
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Table 2. Excluded studies

Author Obwegeser ller & Jo lst Mo Dreeskamp et al. Dordick et al. Flores de Jacoby et al. Rozencweig Yukna et al. Ackermann et al. Bachmann & Bernimoulin Haase et al. Krekeler et al. st Lo Ouhayoun et al. rle Ha Schramm-Scherer & Linder Sbordone et al. Mercier et al. Raghoebar et al. Lauer et al. Shulman Al-Mahdy Al-Belasy schl & Fro Kerscher Carnio & Miller Lauer & Schimming Wei et al. Orsini et al. Sezer et al. de Almeida et al. Luczyszyn et al. Grifn et al. Wessel & Tatakis Year 1967 1972 1973 1976b 1976 1976 1977 1980 1980 1980 1980 1980 1983 1987 1987 1988 1992 1995 1996 1996 1997 1997 1999 2001 2002 2004 2004 2005 2005 2006 2008 Reason for exclusion Description of technique Only descriptive histology No reported data on keratinized tissue No reported data on width of keratinized tissue No control group Insufcient follow-up data; follow-up of 2 months only Insufcient number of patients (4) Fully edentulous patients No control group Retrospective study No control group No data on keratinized tissue No measurements for control group; only descriptive histology No data on keratinized tissue No reported outcomes on the width of keratinized tissue Root coverage procedure No control group; no data on keratinized tissue Only descriptive histology Simultaneously with implant placement Follow-up of only 6 weeks; no control group No control group Fully edentulous patients No control group No control group; only descriptive data Only descriptive histology No measurements for the control group Fully edentulous patients No reported treatment outcomes on width of keratinized tissue, volume or patient-centered outcomes Control group does not use soft tissue augmentation No data on keratinized tissue No reported outcomes on width of keratinized tissue
2000; McGuire & Nunn 2005;Table 6; Fig. 4). The WMD with 95% CI between the allogenic groups (APF/V plus ADMG or HFDDS) and the control groups (APF/V plus FGG) was 28.41% (23.56, 33.26). The mean shrinkage was statistically signicantly greater in the allogenic groups (P 0). The I-squared value of 95.1% indicated a signicant heterogeneity between the two studies (P 0). Width of attached gingiva (Table 7; Fig. 5). Fifteen studies reported data on the width of the attached gingiva including six RCTs, eight CCTs, and one cohort study (Table 7). Based on ve studies, the width of the attached gingiva postoperatively was statistically signicantly greater when APF/V plus autogenous tissue groups were compared with control groups (no treatment) (P 0) (Fig. 5A). The WMD with a 95% CI was 3.94 mm (3.64, 4.23). The I-squared value of 98.4% indicated a signicant heterogeneity between the studies (P 0). The comparison between APF/ V with or without the addition of autogenous tissue revealed a statistically signicant WMD of 0.83 mm (0.42, 1.25) in favor of the groups using autogenous tissue (P 0.01) (Fig. 5B). Again, the I-squared value of 78.4% revealed signicant heterogeneity between the two studies (P 0.01). 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 APF/V alone (Fig. 5C). The comparison between an APF/V with either an FGG or a BCT revealed a statistically signicant difference of 1.52 mm (1.73, 1.31) in favor of the group using the autogenous FGG (P 0) (Fig. 5D). One study comparing an APF/V plus FDS with or without fenestration of the ap demonstrated a statistically signicant WMD of 1.17 mm (0.61, 1.73) in favor of the group using a fenestration of the ap (P 0; Fig. 5E). 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 signicantly greater for an APF/V in combination with lyophilized dura mater (mean 63.1%; SD 9.3) compared with an APF/V with an FGG (20.7%; SD 11.1) (Schoo & Coppes 1976).
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 signicant weighted mean difference (WMD) of 4.49 mm (4.28, 4.71) compared with no treatment (P 0) (Fig. 3A). The Isquare value of 96.6% indicated a statistically signicant heterogeneity between the four studies (P 0). Based on one study reporting on the outcomes of two different APF/V plus SCTG techniques, there was a statistically non-signicant WMD of 0.34 mm ( 0.45, 1.13) favoring method 1 (a partial-thickness ap is raised and the SCTG is taken from below the palatal surface) over method 2 (the SCTG is obtained by the thinning of a full-thickness palatal ap) (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
(0.7 mm; 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 0.85 mm ( 1.71, 0.01) (Fig. 3D). Despite showing a high standard deviation, this mean gain in keratinized tissue was statistically signicantly different in favor of the groups using autogenous tissue (P 0). The I-squared value indicated signicant heterogeneity between the different studies (94.6%; P 0). Fenestration of the ap when using an FDS statistically signicantly improved the gain in keratinized tissue (1.22 mm; 0.71, 1.73; P 0) (Fig. 3E). 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.
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Table 3. Included studies part 1: augmentation of keratinized tissue

Test treatment Control 1 treatment Control 2 Control 3 Follow-up treatment treatment period (weeks) 17 15 30 15 15 Total number of patients Total number of sites Number of sites test group Number of Number sites control 1 of sites group control 2 group Number of sites control 3 group
Author
Year of Study publication design
Diedrich et al. 1972
CCT
Vestibuloplasty
Richter et al. 1973 APF plus SCTG (method 2) APF plus SCTG (method 3) 12 17 10 20 10 10 22 10 12 10 26 8 14 6 6
CCT
Vestibuloplasty
35
12
24
12
12 2
Edel
1974
Cohort Study
Vestibuloplasty with releasing incision Vestibuloplasty without suturing APF plus SCTG (method 1)
CCT Vestibuloplasty
APF plus FGG
APF
Fagan & 1974 Freeman Matthiessen 1974 & Diedrich
CCT
Fagan 1975 Dordick et al. 1976a
CCT RCT
APF APF plus FGG
12 26
10 60
5 30
5 30
1976
CCT
Vestibuloplasty
208
16
1976 Vestibuloplasty/ APF plus FGG 12 14
APF plus FGG
104
58
84 28
16 14
68 14
Lange & Flores de Jacoby Schoo & Coppes James & McFall
1978
Cohort Study CCT
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No treatment No treatment APF plus FGG Vestibuloplasty/ APF plus FDS without fenestration No treatment Vestibuloplasty according to Plagmann APF plus FGG (mucotom very thin) APF plus FGG (mucotom thin) APF plus FGG (mucotom intermediate) Vestibuloplasty/ APF plus FDS with fenestration Vestibuloplasty/ APF plus FGG Vestibuloplasty according to Schmid & rmann Mo APF plus FGG (scalpel)
CCT
Vestibuloplasty extended into horizontal part of ridge APF plus FGG APF with releasing incision plus FGG Vestibuloplasty with releasing incision APF plus lyoph. dura mater Vestibuloplasty/ APF with releasing incision plus FGG APF plus FGG 14 104 12 12 92 31 24 184 148 12 92 76
12 92 72
de Trey & 1980 Bernimoulin Dorfman 1980 et al. Gher et al. 1980
RCT
Cohort Study
CCT
52416 26
34 15
80 30
40 15
40 15
Hangorsky & 1980 Bissada Lange et al. 1981
CCT
rmann Mo et al.
1981
CCT
52
34
89
19
11
29
30
CCT, controlled clinical trial; RCT, randomized-controlled clinical trial; APF, apically positioned ap; SCTG, subepithelial connective tissue graft; FGG, free gingival graft; ADMG, acellular dermal matrix graft; FDS, freeze-dried skin allograft; HF-DDS, human broblast-derived dermal substitute; TEMG, tissue-engineered mucosal graft; BCT, bilayered cell therapy.
Percent shrinkage of graft/grafted area. Seven CCTs, one RCT, and one 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; Mo rmann et al. 1981; Marxer et al. 1982; Po llmann & Scherer 1983). No statistically signicant differences were observed between most of the various treatment modalities (different techniques for vestibuloplasty). A borderline signicance was observed in favor of an 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 o1 mm of attached gingiva (Mo rmann et al. 1981). The FGGs were retrieved using either a mucotom or a blade and with various thicknesses ranging from 0.37 to 0.92 mm. The group with the thickest mean FGG retrieved showed statistically signicantly 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 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 (personal communication); 297 mm2) compared with the test group (vestibuloplasty according to Schmid & Mo rmann 1976; 236 mm2) (Lange et al. 1981). 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 signicant differences were observed between an APF in combination with an FGG (mean 3.9 mm; SD 1.1) compared with an EdlanMejchar ap (3.9 mm; 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 & Mo rmann 1976 procedure (12.5%) than with the Plagmann 1979 procedure (12.2%) (Lange et al. 1981). Patient-reported outcomes and esthetics. Two studies (one CCT, one RCT) reported on postoperative pain (Dordick et al. 1976a; Harris 2001). In one study,
Number of Number sites control 1 of sites group control 2 group
Number of sites control 3 group
11
6 15
15
21
40
32
22
9 9 9 RCT 13 18
Number of sites test group
6 15
21
40
25
32
22
Total number of sites
12 45
42
80
45
64
44
Total number of patients
12 45
21
16
45
32
22
Control 2 Control 3 Follow-up treatment treatment period (weeks)
208
312
26 13
52
26
52
Year of Study publication design
Cohort Study
RCT RCT
RCT
RCT
RCT
RCT
Dorfman 1982 et al. Marxer et al. 1982
2000 2001
1983
1985
Table 3. Continued.
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McGuire & 2005 Nunn Mohammadi 2007 et al. McGuire 2008 et al.
llmann & Po Scherer
Kennedy et al. Wei et al. Harris
Author
RCT
Scaling and root planing Vestibuloplasty/ Vestibuloplasty APF plus FGG according to Edlan & Mejchar Vestibuloplasty/ Vestibuloplasty Vestibuloplasty/APF APF plus plus FGG lyophylised dura mater Vestibuloplasty/ Scaling and root APF plus FGG planing APF plus ADMG APF plus FGG Vestibuloplasty/ Vestibuloplasty/ VestibuloAPF plus ADMG APF plus FGG plasty/APF plus SCTG Vestibuloplasty/ Vestibuloplasty/ APF plus HF-DDS APF plus FGG Vestibuloplasty/ Vestibuloplasty/ APF plus TEMG APF Vestibuloplasty/ Vestibuloplasty/ APF plus BCT APF plus FGG APF plus FGG
Test treatment
Control 1 treatment
26
25
50
25
25
Table 4. Included studies part 2: augmentation of soft tissue volume

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
12 12 6
Author
Year of publication
Study design
Number of patients control 2 group
Allen et al. Studer et al. Batista et al. No treatment
1985 2000 2001
Cohort study Cohort study Case series
SCTG SCTG ADMG
HA FGG
24 14 27
21 30 8
26 30 18
14 12 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

Total number of sites 30 14 184 148 76 72 92 92 92 92 6 6 2 15 15 15 15 17 26 104 8 Number of patients test Number Number of Number Number of Number Follow-up Test of sites patients of sites patients of sites period treatment test control 1 control 1 control 2 control 2 (weeks) Control 1 treatment Control 2 treatment
Author
Year of Study Total publication design number of patients
Diedrich et al. Edel
1972
CCT
15
1974
Dorfman 1980 et al. Gher et al. 1980
Cohort 8 study RCT 92
Vestibuloplasty withVestibuloplasty releasing incision APF plus SCTG APF plus SCTG (method 1) (method 2) APF plus FGG No treatment
APF plus SCTG (method 3)
Cohort 31 study 40 30 15 15 15 15 34 40 34 40
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42 64 45 44 18 50 25 9 9 25 22 22 15 15 15 22 9 25 32 32 32 21 21 21 21 32 15 22 9 25 15
CCT
34
52416 26
Hangorsky 1980 & Bissada Lange 1981 et al.
CCT
15
1982
RCT
21
208 312 15 13 52 13 26
Dorfman et al. Kennedy et al. Harris
1985
RCT
32
2001
RCT
45
RCT
22
RCT
McGuire & 2005 Nunn Moham2007 madi et al. McGuire 2008 et al.
RCT
25
Vestibuloplasty/APF Vestibuloplasty/APF plus FDS with plus FDS without fenestration fenestration Vestibuloplasty/APF No treatment plus FGG Vestibuloplasty Vestibuloplasty according to Schmidaccording to rmann & Mo Plagmann APF plus FGG Scaling and root planing Vestibuloplasty/APF Scaling and root plus FGG planing Vestibuloplasty/APF Vestibuloplasty/APF Vestibuloplasty/ plus ADMG plus FGG APF plus SCTG Vestibuloplasty/APF Vestibuloplasty/APF plus HF-DDS plus FGG Vestibuloplasty/APF Vestibuloplasty/APF plus TEMG Vestibuloplasty/APF Vestibuloplasty/APF plus BCT plus FGG
CCT, controlled clinical trial; RCT, randomized-controlled clinical trial; APF, apically positioned ap; SCTG, subepithelial connective tissue graft; FGG, free gingival graft; FDS, freeze-dried skin allograft; ADMG, acellular dermal matrix graft; HF-DDS, human broblast-derived dermal substitute; TEMG, tissue-engineered mucosal graft; BCT bilayered cell therapy.
154 |
Outcome measure Keratinized tissue (mm) Keratinized tissue (mm) 0.24 0.09 1.2 4.9 1.67 2.91 1.51 6.3 1.67 1.76 1.27 5.08 1.49 6.24 0.19 1.59 0.07 1.66 0.1 0.67 0.34 0.73 Keratinized tissue (mm) Keratinized tissue (mm) Keratinized tissue (mm) Keratinized tissue (mm) Keratinized tissue (mm) 1.5 1.3 0.6 4.1 1.34 1.5 1.33 0.38 1.17 0.97 0.4 0.18 1.79 1.46 1.3 1.07 Change control 2 No difference Signicant Signicant Signicant Signicant Effect of device vs. control 1 0.18 2.4 0.32 0.4 4.1 1 0.91 2.72 0.45 0.1 0.87 6.2 4.7 0.1 1.92 1.4 0.8 0.1 0.59 1.6 4.8 3.91 3.4 4.46 Effect of control 1 vs. control 2 0.11 0.22 1.5 0.09 Keratinized tissue (mm) Keratinized tissue (mm) Keratinized tissue (mm) Keratinized tissue (mm) Keratinized tissue (mm) Postsurgery control 2 3.5 0 SD 23.6 6.5 26.7 1.6 2.13 1.62 3.5 1.33 5.6 4.42 2.1 3.8 1.58 5.6 4.08 1.8 Baseline test SD Postsurgery test SD Change test Change test SD Baseline control 1 SD Postsurgery control 1 SD Change control 1 Change control SD 0.08 0.1 1.16 0.45 0.8 0.32 3.29 Comments 0.38 4.1 1.25 Effect of device vs. control 2 0 Statistics pre- to postoperative Statistics postoperative 8-week results Statistics postoperative Not signicant Not signicant Statistics for change Statistics postoperative Statistics postoperative 0.47 4 0.99 3.6 Signicant Signicant Not signicant Signicant Signicant Signicant negative
Table 5. Continued.
Author
Treatment indication
Diedrich et al. Edel
Dorfman et al.
Gher et al.
Hangorsky & Bissada Lange et al. Dorfman et al.
Kennedy et al. Harris
McGuire & Nunn
Mohammadi et al. McGuire et al.
Author
Vestibuloplasty Inadequate width of keratinized tissue Inadequate width of attached gingiva Inadequate width of keratinized tissue Inadequate width of keratinized tissue Vestibuloplasty Inadequate width of attached gingiva Inadequate width of AG Inadequate width of keratinized tissue Lack of keratinized gingiva Inadequate width of keratinized tissue Inadequate width of keratinized tissue Baseline SD control 2
1.5
Diedrich et al. Edel Dorfman et al. Gher et al. Hangorsky & Bissada Lange et al. Dorfman et al. Kennedy et al. Harris McGuire & Nunn Mohammadi et al. McGuire et al.
0.4
155 |
4 2 favors control group 0 2 4 favors test/active group
Fig. 3. (AE). 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) 96.6%; test for overall effect: z 41.37, P 0. B: signicance test: z 0.84, P 0.401. C: signicance test: z 1.64, P 0.101. D: I-squared 94.6%; test for overall effect: z 1.95, P 0.052. E: signicance test: z 4.69, P 0. APF, apically positioned ap; CI, condence interval.
Table 6. Characteristics of included studies: shrinkage of keratinized tissue
RCT, randomized-controlled clinical trial; ADMG, acellular dermal matrix graft; HF-DDS, human broblast-derived dermal substitute; FGG, free gingival graft; SD, standard deviation.
Number Follow- Test Number Number Number Total Author Year of Study Total treatdesign number of number of patients of sites of patients of sites up publicontrol period ment control test of sites test patients cation (weeks)
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 signicant (Dordick et al. 1976a). In the second study, three treatment modalities were compared for augmentation of keratinized tissue: (i) an ADMG, (ii) an SCTG, and (iii) an FGG. No differences in pain perception were observed between patients treated with ADMG and FGG; however, more pain was reported for SCTG-treated patients compared with ADMG-treated patients (Harris 2001). No signicant differences were observed with respect to postoperative bleeding in an RCT comparing a tissue-engineered skin product (BCT) with an FGG (McGuire et al. 2008). However, there appears to be a difference depending on whether an FGG is placed directly on bone (less bleeding, less swelling) or on the periosteum for postoperative hemostasis and swelling (Dordick et al. 1976a). The overall patient morbidity (pain, swelling, and bleeding) was evaluated in another RCT revealing no differences between the two treatment modalities (HFDDS vs. FGG; McGuire & Nunn 2005). However, subjects treatment preference was signicantly greater in the allograft group (BCT) compared with 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 with control sites (FGG) in two recent studies (McGuire & Nunn 2005; McGuire et al. 2008).
Treatment outcomes (Table 8)
22
In the rst case series, 21 patients with 26 localized alveolar defects were treated either with an SCTG or hydroxylapatite implants. The authors reported that 14 of 14 sites (SCTG) showed some shrinkage within the rst 46 weeks, but that the augmented sites remained stable for 3 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 the vertical ridge width of 0.61 mm (SD 0.77) and in the horizontal ridge width of 1.72 mm (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 an FGG or an 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 treatment modalities were statistically signicant in favor of the SCTG group. The untreated defects showed a slight increase in volume of 6 mm3 (SD 5.4), which was statistically signicantly different compared with the two test groups using autogenous tissue (Studer et al. 2000).
SD Effect Out- SD Outcontrol device vs. come test come control control test
Signicant
12
16
10
Control Treatment Outcome indication measure treatment
Keratinized gingival o1 mm FGG ADMG 26 6
22
52
HF-DDS
FGG
Lack of keratinized gingiva
Percentage shrinkage of keratinized tissue (%) Percentage shrinkage of keratinized tissue (%)
71
45.5
8.9
21.8
8.9
Signicant
22
Discussion
The present systematic review focused on answering the question of whether one method is superior over 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 three studies met the inclusion criteria. No meta-analysis could be performed due to heterogeneity between the studies.
12
44
22
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), and one as a case series (Batista et al. 2001). No meta-analysis could be performed due to heterogeneity in the study design and treatment modalities.
12
RCT
RCT
22
McGuire 2005 & Nunn
2000
Part 1: augmentation of keratinized tissue/ attached gingiva Mean gain in the width of keratinized tissue
Wei et al.
The present review demonstrated the superiority of APF/V plus autogenous

156 |
mean
author control_1
year_of_publication graft_1
difference (95% CI)
Wei et al. ADMG FGG
2000
55.00 (42.50, 67.50)
McGuire & Nunn 2005 FGG
HF-DDS
23.70 (18.44, 28.96)
Overall (I-squared = 95.1%, p = 0.000)
28.41 (23.56, 33.26)
157 |
10 0 favors test/active group 20 40 60 80 favors control group 100
Fig. 4. Meta-analysis of percentage shrinkage of keratinized tissue. Mean difference (%) for test minus control. I-squared (percentage variation attributable to heterogeneity) 95.1%; test for overall effect: z 11.49, P 0. CI, condence interval; ADMG, acellular dermal matrix allograft; FGG, free gingival graft; HF-DDS, human broblast-derived dermal substitute.
158 |
30 15 15 15 15 17 Vestibuloplasty
Table 7. Characteristics of included studies: width of attached gingiva

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
Vestibuloplasty
Author
Year of publication
Study design
Outcome measure
Width of attached gingiva (mm)
Diedrich et al.
1972
CCT
15

24 22 20 10 10 10 10 17 10 10 10 12 12 APF Vestibuloplasty 12 12 12 12 35 Vestibuloplasty Vestibuloplasty Inadequate width of attached gingiva Vestibuloplasty Vestibuloplasty with releasing incision Vestibuloplasty without suturing APF plus FGG 10 10 16 8 8 8 8 208 5 5 5 5 12 APF plus FGG 5 5 5 5 12 Vestibuloplasty extended into horizontal part of ridge APF plus FGG APF APF Vestibuloplasty Inadequate width of attached gingiva No attached gingiva Vestibuloplasty 24 184 148 76 72 92 92 92 92 104 8 12 12 12 12 14 Vestibuloplasty with releasing incision APF plus FGG APF plus FGG No treatment no treatment 40 34 40 34 40 52416 Vestibuloplasty/APF plus FDS with fenestration Vestibuloplasty/APF plus FGG 21 32 6 9 9 6 9 208 312 26 13 APF plus FGG Vestibuloplasty/APF plus FDS without fenestration No treatment 42 64 12 18 9 6 32 32 32 21 21 21 Vestibuloplasty/APF plus FGG APF plus ADMG Vestibuloplasty/APF plus TEMG 25 25 25 26 Vestibuloplasty/APF plus BCT Scaling and root planing Scaling and root planing APF plus FGG Vestibuloplasty/APF 50 25 Vestibuloplasty/APF plus FGG Attached gingivao1 mm Inadequate width of attached gingiva Inadequate width of keratinized tissue Inadequate width of keratinized tissue Inadequate width of attached gingiva Inadequate width of attached gingiva Attached gingivao1 mm Inadequate width of keratinized tissue Inadequate width of keratinized tissue
Richter et al.
1973
CCT
12
1974
CCT
10
Fagan & Freeman Matthiessen & Diedrich
1974
CCT
10
Width of attached gingiva (mm) Width of attached gingiva (mm) Width of attached gingiva (mm)
Fagan
1975
CCT
Fagan
1975
CCT
1976
CCT
Width of attached gingiva (mm) Width of attached gingiva (mm) Width of attached gingiva (mm)
1980
CCT
12
Lange & Flores de Jacoby de Trey & Bernimoulin Dorfman et al. Gher et al.
1980
RCT
92
1980
Cohort study
31
Width of attached gingiva (mm) Width of attached gingiva (mm) Width of attached gingiva (mm) Width of attached gingiva (mm)
Hangorsky & Bissada
1980
CCT
34
1982
RCT
21
Dorfman et al. Kennedy et al. Wei et al.
1985
RCT
32
2000
RCT
12
Mohammadi et al.
2007
RCT
Width of attached gingiva (mm) Width of attached gingiva (mm) Width of attached gingiva (mm) Width of attached gingiva (mm) Width of attached gingiva (mm)
McGuire et al.
2008
RCT
25
CCT, controlled clinical trial; RCT, randomized-controlled clinical trial; APF, apically positioned ap; 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.
Statistics postoperatively
tissue. This information is derived from studies comparing APF/V plus autogenous tissue vs. scaling and root planing and vs. untreated controls. The overall WMD was statistically signicant, despite 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 because 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 signicance compared with 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 signicant 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, an FGG, or an SCTG (Harris 2001). The ADMG was more favorable as the FGG, but was slightly less effective compared with the SCTG. On the other hand, the tissue-engineered grafts (HFDDS, BCT) demonstrated statistically signicantly 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, HFDDS) 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 two studies, where the width of the grafts for control and test sites was held constant (5 mm) (McGuire & Nunn 2005; McGuire et al. 2008). Unfortunately, the rst study does not provide information on the width of the graft that was transplanted (Harris 2001).
Effect of device vs. control 1
Effect of device vs. control 2
Comments
Not signicant Signicant
Change control SD
Signicant Signicant
Signicant Signicant Signicant 0.44 5.57 0.1 0.49 0.7 0.5 6.15 2.3 0.1 0.41 0.4 0.3 0.57 0.3 0.92 2.59 5 3.25 3 0.1 0.26 0.4 Kennedy et al Wei et al. Mohammadi et al. 0.3 0.68 0.2 0.1 0.89 1
Signicant
Signicant
Signicant
0.26
0.46
Change control
0.34
3.33
0.24
3.4 2.6 3.1
2.87
0.07
0.34
SD
Postsurgery control
5 3.8 3.49 6
1.67 1.42
0.11
0.07
0.3
4.13
2.87 3.5
0.36
4.01 1.71
0.38
0.14
0.3
0.25
0.05
Baseline control
SD
0.14
0.97
0.07
0.33
1.6 1.2 0.4 1.6
0.74
0.71
0.8
Change test SD
0.25
0.3
0.38
Change test
0.25
4.37
0.26
3.7 2.8 4.2
4.06
0.41
0.21
0.25
Postsurgery test
SD
4.9 4.3 4.31 5.2
4.13 4
4.71
5.18 3.53
3.67
1.82 1.79
0.27
0.23
4.5
0.05
4.8
0.08
0.07
0.02
Baseline test
SD
1.3 1.5 0.11 1.6
0.08
0.98
0.06
0.13
0.35
0.46
0.91
Table 7. Continued.
Fagan Lange & Flores de Jacoby de Trey & Bernimoulin Dorfman et al.
Diedrich et al. Richter et al. Fagan & Freeman Matthiessen & Diedrich Fagan
0.1
Gher et al. Hangorsky & Bissada Dorfman et al.
0.3
McGuire et al.
Author
0.26
0.14
1.1
0.38
0.85
0.37
0.24
0.14
2.62
0.37
2.37
0.37
Signicant
159 |
160 |
2 favours control group 0 2 4 favours test/active group
Fig. 5. (AE). 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) 98.4%; test for overall effect: z 25.83, P 0. B: I-squared 78.4%; test for overall effect: z 3.91, P 0. C: signicance test: z 1.72, P 0.085. D: signicance test: z 14.33, P 0. E: signicance test: z 4.08, P 0.CI, condence interval; APF, apically positioned ap.
Not mentioned how measurements were performed
Percent shrinkage of keratinized tissue
SCTG, subepithelial connective tissue graft; ADMG, acellular dermal matrix graft; FGG, free gingival graft; NA, not applicable; SD, standard deviation.
Table 8. Characteristics of the included studies: soft tissue volume
14 of 14 sites: shrinkage within rst 46 weeks, then stable for 3 years 159 1.72 0.61 41.4
The meta-analysis revealed statistically signicant less shrinkage for the autogenous control groups (FGG; Table 5; Fig. 3). The reason for the large shrinkage of ADMG compared with 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 bers with scattered elastic bers. The epithelial layer covering the connective tissue showed heterogenous expression of keratinization and a at epithelium connective tissue interface. The epithelium was mostly para- or orthokeratinized toward the gingiva and non-keratinized to the alveolar mucosa. The authors suggested that due to the non-vital matrix of the ADMG, the epitheliumconnective tissue of the surrounding recipient site directed the epithelium differentiation of the ADMG (Wei et al. 2002). These ndings may predominantly explain the high shrinkage of this allogenic dermal matrix. On the other hand, the HF-DDS is obtained from neonatal broblasts 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 with 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, bers, and growth factors.
Shrinkage (descriptive)
Soft tissue volume (mm3)
Gain in horizontal ridge width (mm) Gain in vertical ridge height (mm) % shrinkage horizontal
Localized alveolar ridge defect Localized alveolar ridge defect Localized alveolar ridge defect
Type of defect
Localized alveolar ridge defect Localized alveolar ridge defect
Effect of control 1 vs. control 2
Comments
Outcome measure
Untreated defect
Control 2 treatment
Hydroxylapatite
Control 1 treatment
FGG
Test treatment
SCTG
SCTG
ADMG
ADMG
ADMG
Effect of test vs. control 2
Follow-up period (weeks)
24
14
27
27
27
SD control 2
Number of sites test
Number of patients test
Number of sites control 2
Outcome control 2
12
Number of patients control 2
SD control 1
Number of sites control 1
Number of patients control 1
10 of 12 sites: no shrinkage
Outcome control 1
12
12
12
26
30
18
18
21
30
18
SD test
80 0.59 0.77
104
31
5.4
14
12
18
18
18
Signicant NA NA NA
Effect of test vs. control 1
NA
Signicant
Signicant
Shrinkage of the graft/grafted area
No statistically signicant 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 because the periosteum is known to
Study design
Cohort study
Cohort study
Author Year of publication
1985
2000
2001
2001
2001
Outcome test
Case series
Case series
Case series
Studer et al. Batista et al. Batista et al. Batista et al.
Allen et al.
Studer et al.
Batista et al.
Batista et al.
Batista et al.
Author
Allen et al.
161 |
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 inuence on the shrinkage (Mo rmann et al. 1981). The thickest grafts showed statistically signicantly the least shrinkage. Similar ndings 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 signicantly less shrinkage and greater keratinized tissue than monolayer HF-DDS.
Width of attached gingiva
using the ADMG (Mohammadi et al. 2007). The direct comparison between a tissue-engineered product (BCT) and an FGG, both in combination with an APF/ V, resulted in statistically signicantly more attached gingiva for the autogenous group (FGG) (McGuire et al. 2008). Again, no other control group (APF/V alone) was included. Therefore, the effect of the APF/ V alone could not be calculated.
Patient-reported outcomes and esthetics
between the two sites. Another explanation is that the questionnaires were not administered to the patients until 312 months following the surgery. Important information of the postoperative outcome might have been missed.
The results of the present review indicate that the combination of APF/V plus autogenous tissue is a successful treatment concept with a statistically signicantly greater increase in attached gingiva compared with untreated control groups. The addition of autogenous tissue to an APF/V improved the outcome compared with an APF/V alone. Unfortunately, no studies were identied comparing an APF/V with 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 0.83 mm (0.42, 1.25), and a WMD between APF/V plus autogenous tissue and untreated controls of 3.94 mm (3.64, 4.23), the effect of the APF/V should be around 3 mm. The greatest increase in the 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 signicant based on two included studies. When using an APF/V in combination with an FDS it was found that the fenestration of the ap had a statistically signicant inuence 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
A recent publication evaluating patient outcomes following SCTG and FGG procedures demonstrated that FGG is associated with a greater incidence of donor site pain compared with SCTG at 3 days (Wessel & Tatakis 2008). In the present review, ve included studies reported outcomes on the tolerance 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. 1976a, 1976b). The major advantage of using allogenic grafts instead of 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) signicantly reduced the probability of swelling and bleeding at the donor site (Grifn et al. 2006). The same treatment modalities (ADMG, FGG, and 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 signicant differences were observed with respect to postoperative bleeding in a study comparing a tissueengineered graft (BCT) with an FGG; however, the patients treatment preference was signicantly greater in the allogenic group (BCT; McGuire et al. 2008). The overall patient morbidity (pain, swelling, and 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 difcult for the patients to differentiate
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 signicant differences from 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 signicant decrease in volume (graft shrinkage) between 4 and 14 weeks. Several reasons may be responsible for the low number of studies published in this eld: rst, 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 induce 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, because these grafts tend to show less shrinkage than acellular dermal substitutes. On the other hand, these grafts appear 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
162 |
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 because 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 on cast measurements was applied. For the measurements using method, extensive the so-called Moire appliances are required (Studer et al. 2000). These aspects inuence and limit the clinical applicability. In another study, measurements were performed using a periodontal probe. These measurements may not reect 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 (Mo rmann & 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 were 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). Because 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.
Conclusions
The present systematic review revealed that with respect to increasing the width of keratinized tissue or attached gingiva around teeth, APF/V procedures are successful treatment concepts. The addition of autogenous tissue statistically signicantly 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 the width of keratinized tissue and the width of attached gingiva postoperatively compared with the use of
APF/V plus autogenous tissue. Indeed, allogenic grafts (BCT, HF-DDS) resulted in better color and texture match to surrounding tissue compared with FGGs harvested from the palate. For soft tissue volume augmentation only limited data are available. For localized alveolar defects 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 the current techniques and substitutes in RCT including patient-reported outcome measures and esthetics. Future studies should be conducted to provide long-term data within an observation period of at least 12 months. 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 toward 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 eld.
Acknowledgement: This review has been funded by the Clinic for Fixed and Removable Prosthodontics and Dental Material Science, University of Zurich. No conict of interest is reported for this article.
References
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2009 A Systematic Review Assessing Soft Tissue

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2009 A Systematic Review Assessing Soft Tissue

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Daniel S. Thoma Goran I. Benic Marcel Zwahlen Christoph H. F. Ha mmerle Ronald E.

A systematic review assessing soft tissue augmentation techniques

Date: Accepted 20 May 2009

Thoma et al Soft tissue grafting: a systematic review

Material and methods

Thoma et al Soft tissue grafting: a systematic review

Table 1. Abbreviations used in text, gures, and tables

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

Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146165

Thoma et al Soft tissue grafting: a systematic review

first electronic search: 1471 titles

inter-reader agreement k = 0.82 0.02

inter-reader agreement k = 0.81 0.05

further handsearching 7 articles (references of full text articles)

excluded: 1 excluded: 30 final number of studies included keratinized tissue: 25

final number of studies included soft tissue volume: 3

Part 1: keratinized tissue Treatment outcomes

Thoma et al Soft tissue grafting: a systematic review

Table 2. Excluded studies

Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146165

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

Year of Study publication design

Diedrich et al. 1972

 c 2009 John Wiley & Sons A/S

APF plus FGG

Fagan & 1974 Freeman Matthiessen 1974 & Diedrich

Fagan 1975 Dordick et al. 1976a

APF APF plus FGG

1976 Vestibuloplasty/ APF plus FGG 12 14

APF plus FGG

Cohort Study CCT

Hangorsky & 1980 Bissada Lange et al. 1981

Thoma et al Soft tissue grafting: a systematic review

Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146165

Thoma et al Soft tissue grafting: a systematic review

Number of Number sites control 1 of sites group control 2 group

Number of sites control 3 group

Number of sites test group

Total number of sites

Total number of patients

Control 2 Control 3 Follow-up treatment treatment period (weeks)

Year of Study publication design

Dorfman 1982 et al. Marxer et al. 1982

Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146165

llmann & Po Scherer

Kennedy et al. Wei et al. Harris

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

Number of patients control 2 group

Allen et al. Studer et al. Batista et al. No treatment

1985 2000 2001

Cohort study Cohort study Case series

SCTG SCTG ADMG

 c 2009 John Wiley & Sons A/S

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

Year of Study Total publication design number of patients

Diedrich et al. Edel

Dorfman 1980 et al. Gher et al. 1980

Cohort 8 study RCT 92

APF plus SCTG (method 3)

Hangorsky 1980 & Bissada Lange 1981 et al.

Dorfman et al. Kennedy et al. Harris

Thoma et al Soft tissue grafting: a systematic review

Clin. Oral Impl. Res. 20 (Suppl. 4), 2009 / 146165

c 2009 John Wiley & Sons A/S

c 2009 John Wiley & Sons A/S

c 2009 John Wiley & Sons A/S

c 2009 John Wiley & Sons A/S

c 2009 John Wiley & Sons A/S

c 2009 John Wiley & Sons A/S

c 2009 John Wiley & Sons A/S

c 2009 John Wiley & Sons A/S