DOI: 10.1111/clr.
13920
S Y S T E M AT I C R E V I E W
Efficacy of soft tissue augmentation procedures on tissue
thickening around dental implants: A systematic review and
meta-­analysis
Cristina Valles  | Javi Vilarrasa  | Lucía Barallat | Andrés Pascual | Jose Nart
Department of Periodontology,
Universitat Internacional de Catalunya,
Barcelona, Spain
Correspondence
Cristina Valles, Department of
Periodontology, Universitat Internacional
de Catalunya, C/ Josep Trueta s/n, 08195,
Sant Cugat del Vallès, Barcelona. Spain.
Email: cristinavallveg@uic.es
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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72    
wileyonlinelibrary.com/journal/clr
Abstract
Objectives: The first focused question (FQ1) was: What is the efficacy of connec-
tive tissue graft (CTG), as compared to the absence of soft tissue grafting procedure,
in terms of gain in peri-­implant soft tissue thickness (STT) reported by randomized
controlled clinical trials (RCTs) or controlled clinical trials (CCTs)? The second focused
question (FQ2) was: What is the efficacy of CTG, as compared to soft tissue substi-
tutes, in terms of gain in peri-­implant STT reported by RCTs or CCTs?
Materials and methods: A manual and electronic search was performed for each ques-
tion to identify RCTs and CCTs published up to July 2020. The primary outcome vari-
able was changes in peri-­implant STT and secondary outcomes were marginal bone
level (MBL), clinical parameters for the diagnosis of peri-­implant health, changes in the
position of peri-­implant soft tissues, esthetic outcomes, and patient-­related outcome
measures (PROMs). For primary and secondary outcomes, data reporting mean values
and standard deviations for each study were extracted. Weighted mean differences
(WMDs) or standardized mean differences as well as 95% confidence intervals (CIs)
and prediction intervals (PIs) were calculated.
Results: Eight trials were included to answer the first focused question and eight to
answer the second one, providing data for 254 and 192 patients, respectively. For
the first focused question, a statistically significant difference of 0.64 mm in STT was
found in favor of the grafted group (n = 8; 95% CI [0.16; 1.13]; 95% PI [−1.06; 2.35];
p = .01). Moreover, sites treated with CTG exhibited statistically significant less re-
cession than implants without a graft (n = 4; WMD = 0.50 mm; 95% CI [0.19; 0.80];
95% PI [−0.70; 1.69]; p < .001). For the second focused question, the meta-­analysis
showed a statistically significant gain of STT in the CTG group when compared to
soft tissue substitutes (n = 8; WMD = 0.51 mm; 95% CI [0.28; 0.75]; 95% PI [−0.09;
1.12]; p  < .001). Furthermore, the use of CTG resulted in significantly higher pink
esthetic score values (n = 3; WMD = 1.02; 95% CI [0.29; 1.74]; 95% PI [−3.67; 5.70];
p  = .01) and less recession (n  = 2; WMD = 0.50 mm; 95% CI [0.10; 0.89]; 95% PI
[not estimable]; p = .014) when compared to soft tissue substitutes. No statistically
significant differences between groups were observed for any of the following sec-
ondary variables: MBL, clinical parameters for the diagnosis of peri-­implant health,
Clin Oral Impl Res. 2022;33(Suppl. 23):72–99.
VALLES et al. |
      73

position of the interproximal tissues, keratinized mucosa or PROMS (p > 0.05), except
for medication intake, which was significantly higher when using CTG as compared
to soft tissue substitutes (n = 2; WMD = 1.68; 95% CI [1.30; 2.07]; 95% PI [not esti-
mable]; p < .001).
Conclusions: Soft tissue augmentation procedures are efficacious on soft tissue thick-
ening and, in particular, CTG demonstrated a significant STT gain when compared to
no graft or soft tissue substitutes.

KEYWORDS
dental implants, esthetic outcomes, meta-­analyses, soft tissue thickness, systematic review

1  |  I NTRO D U C TI O N the presence of interdental (Chow et al., 2010) and inter-­implant

Nowadays, both the characteristics and the quantity of peri-­implant
soft tissue around dental implants are acknowledged to be of sig-
nificance for the maintenance of peri-­implant healthy tissues and
successful esthetic outcomes. Recently, Avila-­Ortiz et al. (2020) de-
fined the peri-­implant phenotype as the “morphologic and dimen-
sional features characterizing the clinical presentation of the tissues
that surround and support osseointegrated implants” (i.e., the soft
tissue component—­peri-­implant keratinized mucosa (KM) width, the
mucosal thickness, and the supracrestal tissue height—­and the peri-­
implant bone thickness). Although a recent preclinical study showed
that a buccal bone thickness >1.5 mm is necessary to minimize bone
resorption after implant insertion (Monje et al., 2019), there is limited
clinical evidence regarding the minimum bone thickness required to
obtain predictable stability, esthetics, and health of the peri-­implant
soft tissues (Avila-­Ortiz et al., 2020).
In recent years, the impact of KM width (i.e., distance from the
mucosal margin to the mucogingival junction) and buccal soft tissue
thickness (STT) (i.e., horizontal mucosal thickness) on the mainte-
nance of peri-­implant health has been addressed in some systematic
reviews (Tavelli et al., 2020; Thoma et al., 2018). Although a few au-
thors have found that the absence of KM is not directly associated
with worse peri-­implant conditions (Chung et al., 2006; Wennström
et al., 1994), others have observed higher plaque levels, mucosal in-
flammation, marginal bone loss, and brushing discomfort (Monje &
Blasi, 2019; Perussolo et al., 2018; Roccuzzo et al., 2016) at sites with
lack of adequate KM.
Additionally, the amount of buccal STT plays a critical role in the
achievement of positive esthetic perceptions of dental implants.
Several studies have suggested that a threshold value of 2 mm STT
is advisable to minimize implant or prosthetic component trans-
parency through peri-­implant mucosa (Lops et al., 2017; Sala et al.,
2017). Moreover, it has been claimed that thicker soft tissues may
have a positive influence on mucosal margin stability as they re-
duce the likelihood of mid-­buccal soft tissue recession (Zucchelli
et al., 2018), especially after immediate implant placement (De
Rouck et al., 2008; Evans & Chen, 2008). Likewise, the amount of
STT has been identified as an influencing factor with respect to the
interproximal marginal bone levels (MBLs; Thoma et al., 2018) and
papillae (Chow & Wang, 2010). As a matter of fact, compared with
thinner peri-­implant tissues, thicker tissues have been reported to
favor the appearance of the papilla in the esthetic zone (Chow &
Wang, 2010).
In this context, the use of soft tissue grafting procedures in
conjunction with dental implant therapy has been suggested to
achieve adequate biological, esthetic, and functional outcomes at
those sites lacking KM and/or soft tissue volume (Cairo et al., 2019;
Thoma et al., 2018). It has been reported that the use of autoge-
nous grafts to gain KM not only results in a significant reduction
in probing pocket depth, soft tissue dehiscence, and plaque index
(Tavelli et al., 2020) but also improves bleeding indexes and MBLs
(Thoma et al., 2018). In addition, STT increased by means of autoge-
nous grafts exhibited less marginal bone loss compared with control
non-­grafted sites (Thoma et al., 2018). In this context, autogenous
grafts could be considered the gold standard when performing soft
tissue augmentation procedures for maintenance of peri-­
implant
health (Thoma et al., 2018). On the other hand, substitutes such as
xenogeneic or allogenic dermal matrix have also been contemplated
as possible alternatives to autogenous grafts for KM and mucosal
thickness augmentation (Hutton et al., 2018; Lorenzo et al., 2012)
as patient morbidity may be minimized and the need for a second
surgical site is avoided.
As mentioned above, STT at the site of dental implants appears of
paramount importance for the maintenance of peri-­implant health.
Nonetheless, the impact of different soft tissue grafting techniques
(i.e., autogenous graft and soft tissue substitutes) on the amount of
STT gain and the esthetic appearance is still the subject of research.
Therefore, the purpose of the present systematic review was to criti-
cally assess the evidence on the efficacy of soft tissue augmentation
procedures around dental implants in terms of gain in peri-­implant
STT and esthetic outcomes. To address the aim, the following fo-
cused questions, in the Patient, Intervention, Comparison, Outcome,
and Study Design (PICOS) format, were developed:
PICOS question 1: In systemically healthy humans
with at least one dental implant (immediate or staged
implant), what is the efficacy of connective tissue
graft (CTG), as compared to the absence of a soft
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74      VALLES et al.
tissue grafting procedure, in terms of gain in peri-­
implant STT reported by randomized controlled clini-
cal trials (RCTs) or controlled clinical trials (CCTs)?
PICOS question 2: In systemically healthy humans
with at least one dental implant (immediate or staged
implant), what is the efficacy of CTG, as compared to
soft tissue substitutes, in terms of gain in peri-­implant
STT reported by RCTs or CCTs?
2  |   M ATE R I A L S A N D M E TH O DS
The present systematic review and meta-­
analysis was per-
formed in accordance with the Preferred Reporting Items for
Systematic Review and Meta-­analysis (PRISMA) statement (Liberati
et al., 2009; Moher et al., 2009) and the protocol was registered
in the International Prospective Register of Systematic Reviews
(PROSPERO) (CRD42020201609).
2.1  |  Eligibility criteria
2.1.1  |  Inclusion criteria for studies
• Population: Studies including systemically healthy patients, older
than 18 years, with at least one dental implant requiring an in-
crease in peri-­implant STT.
• Intervention: CTG procedure aimed at increasing STT (simultane-
ous—­at implant placement—­or staged—­after implant placement).
• Comparisons:
a. PICOS question 1: Absence of a soft tissue grafting procedure.
b. PICOS question 2: Soft tissue substitutes aimed at increasing
STT (simultaneous—­
at implant placement—­
or staged—­
after
implant placement).
In this context, PICOS question 1 was developed to assess the
efficacy of CTG [i.e., gold standard (Thoma, Buranawat, et al., 2014)]
in increasing the STT and PICOS question 2 was designed to com-
pare soft tissue substitutes with the gold standard.
• Outcome: Studies reporting data on at least the primary outcome
variable (i.e., peri-­implant STT).
• Study design: RCTs or CCTs with at least 3 months of follow-­up
after the surgical intervention and a minimum of 10 patients (5
patients per group).
2.1.2  |  Exclusion criteria for studies
• Studies evaluating the treatment of peri-­
implant recession
defects.
• Studies investigating peri-­implant STT at pontic sites.
• Studies evaluating pediculated CTG.
• Studies that combined guided bone regeneration and soft tissue
augmentation, in which data regarding changes in peri-­implant
STT could not be obtained.
• Studies in which soft tissue augmentation was conducted before
implant placement.
• Implants with signs of peri-­implantitis.
• Defects requiring bone grafting procedure.
2.2  |  Outcome variables
The primary outcome was changes of the peri-­
implant STT as-
sessed with endodontic instruments, ultrasonic devices, periodontal
probes, or STL image superimposition (i.e., linear measurements).
The secondary outcomes were the following:
implant soft tissue (mm3)
-­ Volumetric changes in the peri-­
-­ Changes in MBL (mm)
-­ Changes in pocket probing depth (PPD) (mm)
-­ Changes in plaque indices
-­ Changes in bleeding indices
-­ Changes in the position of the peri-­implant soft tissues (mm) (level
of the soft tissue margin, clinical crown height, KM dimensions,
level of the papilla)
-­ Shrinkage (%)
-­ Mucosal phenotype changes
-­ Esthetic indices (i.e., professional-­reported esthetic outcomes)
-­ Peri-­implant soft tissue color
-­ Surgical time (min)
-­ Patient-­related outcome measures (PROMs) (i.e., morbidity and
esthetics)
2.3  |  Search strategy
An electronic search was conducted on the following online data-
bases for studies published up to and including July 2020: (i) The
National Library of Medicine (MEDLINE via Pubmed), (ii) Scopus, and
(iii) Cochrane Central Register of Controlled Trials.
The search was conducted using MeSH terms as well as text
words, and Boolean operators (OR, AND) were used to combine
searches. Detailed search strategies were developed for each PICOS
question (Appendices S1 and S2).
Moreover, reference lists of selected studies and previously pub-
lished systematic reviews were manually searched to identify addi-
tional papers (Appendix S3). Also, gray literature of unpublished data
was searched through clinical trials registries (www.clini​caltr​ials.gov
and www.who.int/ictrp/​en/) and Open Grey databases (Appendices
S1 and S2).
The following journals were manually searched online from
January 2000 to July 2020: Journal of Clinical Periodontology,
Clinical Oral Implants Research, Clinical Implant Dentistry and
Related Research, Journal of Periodontology, European Journal of Oral
VALLES et al.
Implantology, Clinical Oral Investigations, International Journal of Oral
and Maxillofacial Surgery, Journal of Oral and Maxillofacial Surgery,
International Journal of Oral and Maxillofacial Implants, International
Journal of Periodontics and Restorative Dentistry, and Implant Dentistry.
2.4  |  Study selection
The search results were entered into the EndNote library (EndNote
X8.1; Thomson Reuters) and duplicates were removed.
Before the beginning of the screening process, the reviewers (CV
and JV) were trained and calibrated to ensure reliability in selecting
articles for inclusion. Previously, a meeting was required to discuss
the eligibility criteria. Subsequently, a random sample of 100 cita-
tions (i.e., 5 blocks of 20 studies) was screened on the basis of title
and abstract and calibration was accepted when a complete agree-
ment was obtained. Discrepancies were resolved by a discussion
between the two reviewers. Then, the full text was independently
screened and the same criteria were applied.
A two-­stage screening process was performed for each PICOS
question. In the first stage, two reviewers (CV and JV) independently
screened the titles and abstracts derived from the electronic and
manual searches. The reasons for rejecting studies at this or at sub-
sequent stages were recorded and a coding scheme for reasons for
exclusion, based on the PICO elements (i.e., population, interven-
tion, comparison, and outcome), was developed and tested prior
to the screening process. If the title and abstract did not provide
sufficient information regarding the inclusion/exclusion criteria,
the full text was obtained as well, along with the selected articles.
Studies selected by at least one reviewer were included in the full-­
text analysis. At the second stage, the final selection of the included
studies was performed based on inclusion/exclusion criteria after
the independent screening of the full-­text articles, and consensus
was obtained through discussion between the two reviewers (CV
and JV). Disagreements were resolved by discussion between all the
authors of this review. All investigations that met the inclusion cri-
teria underwent a validity assessment. Moreover, in cases in which
the results of a study had been published more than once (i.e., differ-
ent reported outcomes or follow-­up), the most complete data were
preferentially selected. To avoid selection bias, the reviewers were
blinded to the study authors, institutions, and journal of publication
at every stage of the screening process. Furthermore, due to time
limitations, only studies published in English were selected.
The inter-­
reviewer reliability (percentage of agreement and
kappa coefficient) was calculated at every stage of the screening
process.
2.5  |  Data extraction
Prior to the data collection process, a standardized data extraction
form for each PICOS question was developed and reviewed by all
authors, and a training exercise was performed to minimize discrep-
ancies between the reviewers.
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      75
Then, data were extracted by two reviewers (CV and JV) under
the supervision of three reviewers (LB, AP, and JN). Any differ-
ences in the data extracted were resolved by discussion between
the five reviewers. In cases of missing or unclear information, the
corresponding authors were contacted by email (maximum three at-
tempts) and asked for clarification.
Information on the following parameters was extracted: au-
thor(s), title, year of publication, study design, study setting, patient/
sample characteristics, interventions, comparisons, and follow-­up.
Furthermore, data on primary and secondary outcomes were ex-
tracted and the evaluation method of each outcome variable was
also registered.
2.6  |  Risk of bias (quality) assessment
The quality of each study was independently assessed by two re-
viewers (CV and JV).
The risk of bias in RCTs was assessed with a revised Cochrane
risk-­of-­bias tool for randomized trials (RoB 2.0) (Sterne et al., 2019).
The following domains were evaluated: (1) risk of bias arising from
the randomization process; (2) risk of bias due to deviations from
the intended interventions; (3) missing outcome data; (4) risk of bias
in the measurement of the outcome; and (5) risk of bias in the selec-
tion of the reported results. Additionally, other potential risks of bias
were also assessed (e.g., funding source).
The risk of bias in non-­randomized clinical trials was evaluated
with the ROBINS-­1 tool (Sterne et al., 2016), which comprises seven
domains: (1) bias due to confounding; (2) bias in the selection of par-
ticipants into the study; (3) bias in classification of interventions; (4)
bias due to deviations from intended interventions; (5) bias due to
missing data; (6) bias in the measurement of outcomes; and (7) bias
in the selection of the reported result.
Again, any disagreement was resolved by discussion between
the two reviewers. To assess inter-­reviewer reliability in quality as-
sessment, the percentage of agreement and kappa coefficient were
calculated.
2.7  |  Data synthesis
For data analysis, change in the peri-­implant STT (i.e., between base-
line and the final examination) was defined as the primary outcome.
For primary and secondary outcomes, data reporting mean values
and standard deviations (SD) [or standard error of the mean (SEM) if
SD could not be obtained] for each study were extracted. Weighted
mean differences (WMD) and 95% confidence intervals (CIs) as well
as 95% prediction intervals (PIs) were calculated for all the outcome
variables except for volumetric changes (CTG vs. substitutes), that
required standardized mean differences (SMD) (Hedges estimator)
calculation since different scales of volumetric measurements were
reported. To calculate the PIs, a minimum of three studies was re-
quired (i.e., not estimable [NE] in meta-­analysis with two studies).
Some studies presented data on STT at different reference points
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76      VALLES et al.

and MBL at mesial and distal sites separately, and in these cases, (<1 year and ≥1 year), and timing of soft tissue augmentation (at im-
the data were combined into a single value following the recom- plant placement or after implant surgery).
mendations of the Cochrane Handbook for Systematic Reviews Forest plots were created to graphically represent the outcomes
of Interventions (Higgins et al., 2020). Additionally, if standard de- of the different analyses. All the statistical analyses were conducted
viations of the difference from final to baseline (changes) were not using STATA v.16 (StataCorp LLC, College Station, Texas, USA) soft-
provided by the authors, an imputation was carried out assuming a ware. Statistical significance was defined as a p-­value < .05.
correlation coefficient of 0.5 (Philbrook et al., 2007) using the fol-
lowing formula:
3  |  R E S U LT S
√
2 2
( )
SDE,change = SDE, base line
+ SDE, final
− 2 × Corr × SDE, base line × SDE, final
3.1  |  Study selection
Cochran's Q test (Cochran, 1954) was performed to assess
the degree of heterogeneity among studies and the I2 index The study selection process is illustrated in the PRISMA flow diagrams
(Higgins et al., 2003) was used to describe the percentage of vari- (Figure 1) and reasons for exclusion are detailed in Appendix S4.
ation across studies due to heterogeneity (I2 = 25%: low hetero-
geneity; I2  = 50%: moderate heterogeneity; and I2  = 75%: high
heterogeneity). The study-­s pecific estimates were pooled using 3.2  |  Focused question 1 (CTG vs. no soft tissue
both the fixed and random-­e ffect models (restricted maximum grafting)
likelihood method), and the random-­e ffect model results were
presented. 3.2.1  |  Search results
Publication bias was evaluated using Funnel plots and Begg's
test. A sensitivity analysis was performed to explore the contribu- Initially, 597 records were identified by the search of electronic data-
tion of each study to the totality of the evidence after omitting one bases and 72 by the search of other sources (i.e., gray literature and
study at a time. unpublished articles). After removing duplicates, a total of 494 stud-
In addition, subgroup analyses were performed based on the ies were screened by title and abstract. Of these, 464 were excluded.
protocol of implant placement (immediate and delayed), follow-­up An additional manual search identified four more potentially eligible

F I G U R E 1  (a) Flow-­chart on the search and selection process for PICOS 1. *Inter-­reviewer agreement = 99.40%; kappa = 0.893; 95% CI
(0.773; 1.013); p < .001. **Inter-­reviewer agreement = 95%; kappa = 0.898; 95% CI (0.704; 1.091); p < .001. (b) Flow-­chart on the search
and selection process for PICOS 2. *Inter-­reviewer agreement = 98.40%; kappa = 0.897; 95% CI (0.817; 0.979); p < .001. **Inter-­reviewer
agreement = 100%; kappa = 1; 95% CI (1; 1); p < .001
VALLES et al.
articles. Accordingly, 21 full-­text articles were obtained. Of these,
12 studies were excluded since they did not meet the strict inclu-
sion and exclusion criteria. Eventually, nine articles, which reported
data from eight studies [two publications (Puzio et al., 2018, 2020)
showed different outcome variables from the same population] were
used for data extraction.
3.2.2  |  Study characteristics
Study design
Table 1a describes the general information of the selected studies.
All studies were published between 2010 and 2020 and, except
for one CCT (Hosseini et al., 2020), all were RCTs: four had a two-­
arm parallel design (Jiang et al., 2020; Migliorati et al., 2015; van
Nimwegen et al., 2018; Papapetros et al., 2019), one a split-­mouth
design (Wiesner et al., 2010), and two included more than one ex-
perimental group (i.e., three-­arm studies: no graft, CTG, and colla-
gen matrix) (Frizzera et al., 2019; Puzio et al., 2018). All studies were
conducted in a university environment except for two, which were
done in a private setting (Migliorati et al., 2015; Wiesner et al., 2010).
Study population and follow-­up
The included studies provided data for 271 patients treated with
a total of 297 implants (155 implants corresponded to the control
group and 142 to the CTG group). Sample size within studies ranged
from 10 (Wiesner et al., 2010) to 60 patients (van Nimwegen et al.,
2018). The mean follow-­up period was 19.71 ± 18.56 months, rang-
ing from 3 (Papapetros et al., 2019) to 60 months (Hosseini et al.,
2020). During follow-­up, nine dropouts were registered, including
for the following reasons: two due to inability to establish contact
(Jiang et al., 2020), two for personal reasons (Papapetros et al.,
2019), three for non-­compliance (Hosseini et al., 2020; Migliorati
et al., 2015), and two due to early implant failure (van Nimwegen
et al., 2018). Furthermore, van Nimwegen et al. (2018) excluded eight
cases because of the lack of precision of the stone casts and Hosseini
et al. (2020) excluded one control implant due to the necessity of
a soft tissue graft. Thus, the final sample consisted of 254 patients
(144 and 133 implants in the control and CTG group, respectively).
Information relating to patient characteristics is shown in Table 2a.
Data relating to gender distribution and age, either as a range
or as a mean, were reported in all studies by treatment group (Jiang
et al., 2020; van Nimwegen et al., 2018; Papapetros et al., 2019;
Puzio et al., 2018, 2020) or for the whole sample (Frizzera et al.,
2019; Hosseini et al., 2020; Migliorati et al., 2015; Wiesner et al.,
2010). Regarding smoking habits, five investigations (Hosseini et al.,
2020; Jiang et al., 2020; Migliorati et al., 2015; Papapetros et al.,
2019; Puzio et al., 2018) included smokers.
Site and implant characteristics
The mucosal phenotype was assessed in only three studies by
means of the transparency of the probe (Frizzera et al., 2019; van
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      77
Nimwegen et al., 2018) and the height of the keratinized gingiva at
the reference central incisor (Migliorati et al., 2015).
Regarding implant design and dimensions, implant brands varied
among the studies and implant diameter was only reported in four arti-
cles (range 3.25–­4 mm). The majority of the studies focused on the es-
thetic area (maxillary premolars, canines, and incisors); two also included
mandibular anterior sites (Papapetros et al., 2019; Puzio et al., 2018) and
maxillary and mandibular molars (Papapetros et al., 2019), and one in-
vestigation only included mandibular premolar and molar sites (Wiesner
et al., 2010). Site and implant characteristics are summarized in Table 2a.
Surgical interventions and provisionalization
Regarding the timing of implant placement, immediate implants
were placed in four studies (Frizzera et al., 2019; Jiang et al., 2020;
Migliorati et al., 2015; van Nimwegen et al., 2018). One of these
studies included intact buccal bone walls as an inclusion criterion
(Jiang et al., 2020), while two accepted buccal bone dehiscences
up to 3 mm at the time of tooth extraction (Migliorati et al., 2015;
van Nimwegen et al., 2018) and one selected only sites with buccal
wall dehiscence (Frizzera et al., 2019). These four studies followed
a flapless approach, filled the gap with a graft, performed soft tis-
sue grafting, and placed a provisional restoration in the same surgi-
cal procedure. Additionally, Frizzera et al. (2019) covered the buccal
bone defect with a bone graft (i.e., xenograft) and non-­cross-­linked
membrane.
In those studies with a delayed protocol (Hosseini et al., 2020;
Papapetros et al., 2019; Puzio et al., 2018; Wiesner et al., 2010), a
flap was raised to place the implants. In two of these studies, si-
multaneous guided bone regeneration was performed, with soft tis-
sue augmentation at 2–­3 months (Hosseini et al., 2020) or 3 months
(Puzio et al., 2020) afterward. In the other two studies (Papapetros
et al., 2019; Wiesner et al., 2010), soft tissue augmentation was per-
formed at the time of implant placement, using a two-­stage protocol.
No implant-­supported provisional restoration was placed in any of
these four studies.
The preferred donor site for CTG harvesting was the palate ex-
cept in one study, where the grafts were obtained from the tuberos-
ity (van Nimwegen et al., 2018).
3.3  |  Effects of intervention
Table 3a shows all the relevant outcomes from the included studies.
3.3.1  |  Primary outcome: STT changes
Methodology of assessment
Changes in peri-­implant STT were assessed with different methodolo-
gies: superimposition of STL files (Jiang et al., 2020; van Nimwegen
et al., 2018), transmucosal probing with an endodontic file and a rub-
ber stopper (Hosseini et al., 2020; Migliorati et al., 2015; Wiesner et al.,
TA B L E 1 A  Methodological characteristics of the selected studies comparing connective tissue graft and no soft tissue graft
|

Follow-­up Control Test Test Level of

78     

References Study design Setting (months) group group 1 group 2 Funding analysis Study outcomes measured

Frizzera et al. RCT (three-­ University 12 NSTG CTG XCM Brazilian agencies FAPESP and CNPq. Patient STT (2 mm below the buccal mucosal
(2019) armed) Conexão Sistemas de Prótese and margin), STL, mesial and distal
Geistlich Pharmaceutical provided papilla, buccal MBL, buccal bone
the materials used thickness, esthetic outcomes
Hosseini et al. CCT University 60 NSTG CTG KOF/Calcin Foundation of The Danish Implant STT (1 and 3 mm below the margin
(2020) Dental Association of the crown at the buccal
aspect), dimensional changes,
plaque scores, bleeding scores,
PPD, KM, STL, interproximal
MBL, peri-­implant color changes,
esthetic outcomes
Jiang et al. RCT (parallel) University 6 NSTG CTG Grants from National Key Research and Patient STT (1–­5 mm below the buccal
(2020) Development Project and Capital´s mucosal margin), STL, buccal
Funds for Health Improvement and plate resorption, buccal bone
Research thickness
Migliorati et al. RCT (parallel) Private 24 NSTG CTG NR Patient STT (at the middle of the apico-­
(2015) coronal width of the keratinized
tissue), plaque scores, bleeding
scores, PPD, KM, clinical crown
height, interproximal MBL,
esthetic outcomes
Papapetros RCT (parallel) University 3–­4 NSTG CTG NR Patient STT (at the alveolar crest and at 2
et al. (2019) and 4 mm apical to the alveolar
crest on the buccal and lingual
aspects), KM, MBL, the thickness
of the buccal and lingual bone
Puzio et al., RCT (three-­ University 12 NSTG CTG XCM Geistlich Pharma AG and Camlog Implant STT (at the level of the cemento-­
2018 armed) Foundation enamel junction of adjacent
Puzio et al. teeth and at the level of the
(2020) mucogingival junction of the
implant)
STT (at the level of the cemento-­
enamel junction of adjacent
teeth and at the level of the
mucogingival junction of the
implant), interproximal MBL
VALLES et al.
VALLES et al. |
      79

2010), bone sounding (Papapetros et al., 2019), and ultrasonography

crest at buccal and lingual sites),

satisfaction, patient preference)

margin), volume, plaque scores,

Note: RCT, randomized clinical trial; CCT, controlled clinical trial; NSTG, no soft tissue graft; CTG, connective tissue graft; XCM, xenogeneic collagen matrix; NR, not reported; STT, soft tissue thickness;
bleeding scores, PPD, mucosal

STT (1 cm below the center of the

(Puzio et al., 2018). Moreover, in the three-­arm study performed by

interproximal MBL, esthetic

inflammation, STL, esthetic
outcomes, PROMs (patient

outcomes, PROMs (patient

STT (1–­2 mm below the crown
Frizzera et al. (2019), linear measurements on cone-­beam computed

Study outcomes measured

tomography (CBCT) scans were performed.

Synthesis of the results

satisfaction)
All studies were included in the meta-­analysis; when the results of
an investigation had been published more than once, the publication
that provided the most complete data was considered (Puzio et al.,
2018). A statistically significant difference of 0.64 mm in STT was
found in favor of the grafted group (n = 8; 95% CI [0.16; 1.13]; 95%
analysis

PI [−1.06; 2.35]; p = .01). The heterogeneity across the studies was

Level of

Patient

Patient

high (I2 = 88.97%; T2 = 0.42) (Figure 2).

When evaluating the subgroups depending on the implant place-
ment protocol, the timing of soft tissue grafting, or the follow-­up,
Grant from Nobel Biocare Services AG

PPD, probing pocket depth; KM, keratinized mucosa; STL, soft tissue level; MBL, marginal bone level; PROMs, patient-­reported outcomes measures
no statistically significant differences were found in terms of STT
changes between the subgroups (Table 4a).

Publication bias
No publication bias for STT changes was observed (t = 0.33; p = 1)
and the sensitivity analysis showed that the removal of a single study
did not alter the results.
Funding

NR

3.3.2  |  Secondary outcomes

group 2

Volumetric changes
Test

When comparing the CTG with the control group, only one study
evaluated volumetric changes (van Nimwegen et al., 2018). In this
group 1

particular study, data were obtained from the superimposition

CTG

CTG
Test

of STL files, and no statistically significant difference was found

(9.32  ± 7.19 and 7.77 ± 7.26 mm3 in the test and control group,
respectively).
Control
group

NSTG

NSTG

Additionally, none of the studies assessed the volumetric shrink-

age over time.
Follow-­up
(months)

Marginal bone level changes

Interproximal MBL changes were measured in five studies that com-
12

12

pared CTG with no graft by means of standardized periapical X-­rays

(Hosseini et al., 2020; Migliorati et al., 2015; Papapetros et al., 2019;
Puzio et al., 2020; Wiesner et al., 2010) and customized bite blocks
University
Setting

Private

(Hosseini et al., 2020; Migliorati et al., 2015; Papapetros et al., 2019;

Wiesner et al., 2010).
Interproximally, MBL changes ranged from 0.12 to 0.86 mm in
the control group, and from 0.09 to 0.79 mm in the CTG group. The
RCT (parallel)
Study design

RCT (split-­
mouth)

meta-­analysis showed no significant differences in MBL changes be-

TA B L E 1 A  (Continued)

tween CTG and no soft tissue graft (n = 5; WMD = −0.01 mm; 95% CI

[−0.13; 0.11]; 95% PI [−0.32; 0.29]; p = .85) (I2 = 24.93%; T2 = 0.01).
Moreover, three studies assessed the hard tissue remodeling at
van Nimwegen

Wiesner et al.

the buccal aspect, measuring the distance between the implant plat-
References

(2018)

(2010)

form and the first radiographically visible bone-­to-­implant contact

et al.

(fBIC) (Frizzera et al., 2019; Papapetros et al., 2019) or the percent-

age of buccal plate resorption length (Jiang et al., 2020). The authors
TA B L E 1 B  Methodological characteristics of the selected studies comparing connective tissue graft and soft tissue substitutes
|

Follow-­up Control Test Test Level of

80     

References Study design Setting (months) group group 1 group 2 Funding analysis Study outcomes measured

Cairo et al. (2017) RCT (parallel) University 6 CTG XCM Self-­funded by the authors Patient STT (1 mm coronal to the
and their institution and mucogingival junction), plaque
a research grant from scores, bleeding scores, PPD, KM,
Geistlich Pharma AG STL, interproximal MBL, surgical
time, PROMs (perception of
procedure, pain during surgery,
medication intake, postoperative
pain, patient satisfaction,
esthetics)
Frizzera et al. (2019) RCT (three-­ University 12 NSTG CTG XCM Brazilian agencies FAPESP and Patient STT (2 mm below the buccal mucosal
armed) CNPq. Conexão Sistemas margin), STL, mesial and distal
de Prótese and Geistlich papilla, buccal MBL, buccal bone
Pharmaceutical provided the thickness, esthetic outcomes
materials used
Hutton et al. (2018) RCT (parallel) University 4 CTG ADM Grant from BioHorizons Patient STT (1, 3, and 5 mm below the buccal
and University of Iowa mucosal margin), KM, modified
Department of Periodontics wound healing index, PROMs
Graduate Student Research (postoperative pain, patient
Fund. BioHorizons provided satisfaction)
the implant components and
the ADM samples
Kamal et al. (2020) RCT (parallel) University 9 CTG PRF Self-­funded Patient STT (2 mm coronal to the
mucogingival junction), KM,
interproximal MBL, esthetic
outcomes, PROMs (postoperative
pain, postoperative swelling,
patient satisfaction)
Puzio et al., 2018 RCT (three-­ University 12 NSTG CTG XCM Geistlich Pharma AG and Implant STT (at the level of the cemento-­
Puzio et al. (2020) armed) Camlog Foundation enamel junction of adjacent
teeth and at the level of the
mucogingival junction of the
implant)
STT (at the level of the cemento-­
enamel junction of adjacent
teeth and at the level of the
mucogingival junction of the
implant), interproximal MBL
Schmitt et al. (2020) CCT University 6 CTG XCM Grant from Botiss Biomaterials Patient STT (region of interest selected for
each augmented site) and volume
VALLES et al.
 VALLES et al.

TA B L E 1 B  (Continued)

Follow-­up Control Test Test Level of

References Study design Setting (months) group group 1 group 2 Funding analysis Study outcomes measured

Thoma et al. (2016) RCT (parallel) University 90 days CTG XCM Clinic of Fixed and Removable Patient STT, plaque scores, bleeding
Thoma et al. (2020) 36 months Prosthodontics and Dental scores, PPD, KM, STL, surgical
Material Science (University time, PROMs (medication
of Zurich) and Geistlich intake, postoperative pain,
Pharma AG oral health impact profile),
histomorphometric analysis
STT (1 mm below the buccal mucosal
margin), profilometric changes of
the soft tissues, plaque scores,
bleeding scores, PPD, KM, papilla
fill, STL, interproximal MBL,
esthetic outcomes, PROMs (oral
health impact profile)
Ustaoğlu et al. (2020) RCT (parallel) NR 3 CTG T-­PRF NR Patient STT (at the level of the alveolar crest,
at midbuccal mucosal level, and
1 mm above the mucogingival
junction), KM, interproximal MBL

Note: RCT, randomized clinical trial; CCT, controlled clinical trial; NR, not reported; NSTG, no soft tissue graft; CTG, connective tissue graft; XCM, xenogeneic collagen matrix; ADM, acellular dermal
matrix; PRF, platelet rich fibrin; T-­PRF, titanium-­prepared platelet rich fibrin; STT, soft tissue thickness; PPD, probing pocket depth; KM, keratinized mucosa; STL, soft tissue level; MBL, marginal bone level;
PROMs, patient-­reported outcomes measures
|
      81
 |
82      VALLES et al.
reported no statistically significant differences between CTG and
no graft (Frizzera et al., 2019; Jiang et al., 2020), with the exception
of Papapetros et al. (2019), who observed a significantly greater dis-
tance from the implant platform to the fBIC at the buccal aspect of
those implants with thin mucosa (i.e., ≤2.5 mm) that were placed in
conjunction with a CTG.
Clinical parameters for the diagnosis of peri-­implant health
Periodontal parameters (i.e., PPD as well as plaque and bleeding indi-
ces) were hardly recorded for comparisons between control and CTG
groups (Hosseini et al., 2020; Migliorati et al., 2015; van Nimwegen
et al., 2018), and meta-­analyses failed to reach statistically significant
differences for any of these outcomes (Appendix S5).
Changes in the position of peri-­implant soft tissues
Changes in the level of the soft tissue margin were evaluated in three
studies that compared CTG versus no graft using an image software
on standardized photographs (van Nimwegen et al., 2018) or STL files
(Jiang et al., 2020) and, clinically, with a dental ruler (Hosseini et al.,
2020). Furthermore, in the three-­arm study by Frizzera et al. (2019),
clinical pictures were analyzed with software. The meta-­analysis
showed statistically significant differences between the control and
CTG groups (n = 4; WMD = 0.50 mm; 95% CI [0.19; 0.80]; 95% PI
[−0.70; 1.69]; p < .001) (I2 = 54.51%; T2 = 0.05), in favor of CTG.
Data on clinical crown height was reported in only one study that
addressed the efficacy of CTG. The results showed a mean clinical
crown height of 8.6 and 8.7 mm for the CTG and the control group
at baseline, respectively (Migliorati et al., 2015). At a 2-­year examina-
tion, the length of the clinical crown height had not changed signifi-
cantly in either group (CTG group: 9.1 mm; control group: 9.6 mm).
Regarding the position of the interproximal tissue, two studies
compared the control and CTG groups with respect to the height
of the papilla (Frizzera et al., 2019; Migliorati et al., 2015). The re-
sults of the meta-­
analysis did not reveal statistically significant
differences in changes in mesial (n  = 2; WMD =  −0.10  mm; 95%
CI [−0.54; 0.34]; 95% PI [NE]; p  = .66) (I2  = 0%; T2  = 0) or distal
(n = 2; WMD = 0.02 mm; 95% CI [−0.32; 0.37]; 95% PI [NE]; p = .89)
2 2
(I  = 0%; T  = 0) papilla height between the groups.
Furthermore, one study (Hosseini et al., 2020) evaluated the
presence of papilla at mesial and distal sites by means of the papilla
index (Jemt, 1997) and no statistically significant differences were
observed between the groups.
The KM was assessed in three (Hosseini et al., 2020; Migliorati
et al., 2015; Papapetros et al., 2019) studies evaluating the efficacy
of CTG. The meta-­analysis revealed no significant differences in
changes in the KM when comparing the CTG and the control group
(n = 3; WMD = 0.38 mm; 95% CI [−0.24; 0.98]; 95% PI [−3.58; 4.33];
p = .23) (I2 = 0%; T2 = 0).
Esthetic outcomes
With respect to professional-­reported esthetic outcomes, five stud-
ies included an esthetic evaluation of the different treatment mo-
dalities (i.e., CTG vs. no graft) on photographs by means of the pink
esthetic score (PES) (Fürhauser et al., 2005) (Frizzera et al., 2019;
van Nimwegen et al., 2018; Wiesner et al., 2010), the PES proposed
by Belser et al. (2009) (Migliorati et al., 2015), or the Copenhagen
Index Score (CIS) (Hosseini et al., 2020). In addition, one investiga-
tion reported each item of the PES separately (van Nimwegen et al.,
2018). Meta-­analysis failed to show any significant difference in PES
between the CTG and the control group (n = 3; WMD = 1.18; 95% CI
[−0.56; 2.91]; 95% PI [−19.73; 22.08]; p = .18) (I2 = 82.87%; T2 = 1.93).
Patient-­reported outcomes in terms of esthetics were evaluated
in one study at the end of the examination period (van Nimwegen
et al., 2018). The authors did not find statistically significant differ-
ences between no graft and CTG in terms of color or shape of the
peri-­implant mucosa.
Color of peri-­implant mucosa
Only one study evaluated the changes in color of the peri-­implant
mucosa using a spectrophotometer at a 5-­year follow-­up (Hosseini
et al., 2020). The results showed significantly less color change at
implant sites with CTG as compared to no graft (0.57 ± 4.35 and
2.17 ± 3.38, respectively).
Patient-­related outcomes
When comparing autogenous graft and no soft tissue augmentation
procedure, none of the studies evaluated discomfort and pain per-
ceived by patients after harvesting a CTG from the palate. Overall
patient satisfaction was evaluated in two studies and no differences
were observed between the groups (van Nimwegen et al., 2018;
Wiesner et al., 2010).
3.4  |  Quality assessment of the included studies
Results in respect of quality assessment are shown in Figure 3 and
detailed information for each criterion is depicted in Appendix S6.
The quality assessment identified only one study with a low risk
of bias (Puzio et al., 2018); most of the investigations presented some
concerns in one (Frizzera et al., 2019; Jiang et al., 2020; Migliorati
et al., 2015; Papapetros et al., 2019) or two domains (Van Nimwegen
et al., 2018), mainly related to the randomization process, outcome
measurements, and/or selection of the reported results. Moreover,
the study of Wiesner et al. (2010) demonstrated a high risk of bias
for one criterion (i.e., measurement of the outcome) (Figure 3a), and
the non-­randomized study was at critical risk of bias due to the se-
lection of participants (Hosseini et al., 2020).
3.5  |  Focused question 2 (CTG vs. substitutes)
3.5.1  |  Search results
After discarding duplicates, a total of 441 studies were identified
by the search of electronic databases and clinical trial registries.
Screening by title and abstract identified 17 eligible articles for
 VALLES et al.

TA B L E 2 A  Sample, implant, and intervention characteristics of included studies comparing connective tissue graft and no soft tissue graft

Baseline
Gender patients Final patients
Mean age (range) (% females) Smoking habit (implants) (implants)
Timing of Timing of soft
Test/Control Test/Control Test/Control implant Type of implant and tissue grafting
References *Global *Global *Global Test/Control Test/Control placement position and donor site Provisionalization

Frizzera et al. Test 1: 40.25 Test 1: 87.5 Smokers were Test 1: 8 (8) Test 1: 8 (8) Immediate Conexão Sistemas de At implant Day of implant surgery
(2019) Test 2: 44.1 Test 2: 50 excluded Test 2: 8 (8) Test 2: 8 (8) Prótese placement
Control: 43.63 Control: 75 Control: 8 (8) Control: 8 (8) 12–­22
Hosseini et al. 22 (18–­31)* 57.89* 15.79* (10)/(23) (8)/(20) Delayed Astra Tech Implant 2–­3  months No
(2020) System after implant
Anterior MX surgery
Jiang et al. (2020) 34.3 (25–­51)/37.7 60/45 10/5 21 (21)/21 20 (20)/20 (20) Immediate Nobel Biocare At implant Within 24h after
(20–­66) (21) 12–­22 placement implant surgery
Migliorati et al. 47.5 (22–­70)* 52.08* 4.17* 24 (24)/24 24 (24)/23 (23) Immediate Straumann At implant Day of implant surgery
(2015) (24) 14–­24 placement
Papapetros et al. 50 (27–­78)/47 56.52/60.87 21.74/26.09 24 (24)/24 23 (23)/23 (23) Delayed Biomet 3i At implant Tooth-­supported
(2019) (23–­72) (24) Anterior/Posterior placement provisional
and MX/MB restoration
Puzio et al. Test 1: 41.1 Test 1: 40 Test 1: 13.3 Test 1: 13 (15) Test 1: 13 (15) Delayed Camlog 3 months after No implant-­supported
(2018, 2020) (19–­59) Test 2: 66.7 Test 2: 0 Test 2: 12 Test 2: 12 (15) Anterior region (first implant provisional
Test 2: 42.1 Control: 60 Control: 0 (15) Control: 15 (15) PM to first PM) surgery restoration
(19–­6 4) Control: 15 of MX/MB
Control: 43.3 (15)
(20–­65)
van Nimwegen 45.5 (19.5–­ 56.67/50 Smokers were 30 (30)/30 25 (25)/25 (25) Immediate Nobel Biocare At implant Day of implant surgery
et al. (2018) 67.8) /47.8 excluded (30) 14–­24 placement
(20.9–­82.2)
Wiesner et al. 39 (25–­60)* 70* Smokers were 10 (10)/10 10 (10)/10 (10) Delayed Neoss Dental At implant No
(2010) excluded (10) Implant System placement
PM and molar of MB
Note: MX, maxilla; MB, mandible; PM, premolar Test 1, connective tissue graft; Test 2, collagen matrix; Control, no graft
|
      83
TA B L E 2 B  Sample, implant, and intervention characteristics of included studies comparing connective tissue graft and soft tissue substitutes
|

Baseline Final
84     

Gender (% patients patients

Mean age (range) females) Smoking habit (implants) (implants)
Timing of Timing of soft tissue
Test/Control Test/Control implant Type of implant and grafting and donor
References Test/Control *Global *Global *Global Test/Control Test/Control placement position site Provisionalization

Cairo et al. 50.3 (21–­73)/48.3 67/24 30/20 30 (30)/30 28 (28)/30 Delayed Astra Tech Implant At the second-­stage After soft tissue
(2017) (22–­69) (30) (30) System/Straumann augmentation, 30
MX/MB patients received
a temporary
crown placed at
3.9 months
Frizzera et al. Test 1: 40.25 Test 1: 87.5 Smokers were Test 1: 8 (8) Test 1: 8 (8) Immediate Conexão Sistemas de At implant Day of implant
(2019) Test 2: 44.1 Test 2: 50 excluded Test 2: 8 (8) Test 2: 8 (8) Prótese placement surgery
Control: 43.63 Control: 75 Control: 8 (8) Control: 8 (8) 12–­22
Hutton et al. 59.7/51.2 40/50 Non-­smokers 10 (10)/10 10 (10)/10 Delayed BioHorizons At implant No implant-­supported
(2018) (6 months (10) (10) Single-­rooted tooth placement provisional
before (except for MB
study incisors)
onset)
Kamal et al. 41/37 83.33* Smokers were 6 (6)/6 (6) 6 (6)/6 (6) Delayed Neobiotech At implant No
(2020) excluded Maxillary tooth in placement
the esthetic zone
including PM
Puzio Test 1: 41.1 (19–­59) Test 1: 40 Test 1: 13.3 Test 1: 13 (15) Test 1: 13 Delayed Camlog 3 months after No implant-­supported
et al. (2018, Test 2: 42.1 (19–­6 4) Test 2: 66.7 Test 2: 0 Test 2: 12 (15) (15) Anterior region (first implant surgery provisional
2020) Control: 43.3 Control: 60 Control: 0 Control: 15 Test 2: 12 PM to first PM) of restoration
(20–­65) (15) (15) MX/MB
Control. 15
(15)
Schmitt et al. 50.3/42.3 42.86/28.57 Smokers were 7 (7)/7 (7) 7 (7)/7 (7) Early Different type of At the second-­stage One-­ and
(2020) excluded implants three-­month
The location of the follow-­up visits in all
augmented regions patients
was 12–­23 and 43
Thoma et al. 44.1/43.4 70/60 0/1 cig/day 10 (10)/10 8 (8)/9 (9) Delayed Astra Tech Implant After implant Temporary removable
(2020) (10) System/Straumann placement partial dentures
(bone level) (3 months before
Second PM to second the abutment
PM of MX and MB connection)
Ustaoğlu et al. 37.67/39.13 53.33/66.67 Smokers were 15 (15)/15 15 (15)/15 Delayed Semados At implant NR
(2020) excluded (15) (15) Incisor, canine and PM placement
Note: MX, maxilla; MB, mandible; PM, premolar; NR, not reported Test 1, connective tissue graft; Test 2, collagen matrix; Control, no graft
VALLES et al.
VALLES et al.
full-­text reading and seven additional papers were obtained through
manual search. Of these, ten articles were selected, reporting data
from eight investigations [two groups of papers showed different
outcome variables (Puzio et al., 2018, 2020; Thoma et al., 2016,
2020) and different follow-­up (Thoma et al., 2016, 2020) from the
same study population].
3.5.2  |  Study characteristics
Study design
Table 1b summarizes the main features of the selected studies.
The included studies were published between 2017 and 2020.
Seven studies were single-­center, parallel RCTs that compared dif-
ferent soft tissue substitutes with CTG and two of them, as men-
tioned above, also included a negative control group in which no
grafting procedure was performed (Frizzera et al., 2019; Puzio et al.,
2018). Moreover, one study was a CCT (Schmitt et al., 2020). Seven
studies were carried out in a university setting and one did not re-
port the setting (Ustaoğlu et al., 2020).
Study population and follow-­up
At baseline, the pooled sample consisted of 197 patients, 98 cor-
responding to the comparison group and 99 to the CTG group, with
a total of 202 implants placed (101 in the experimental and 101 in
the CTG group). The number of patients in each study varied be-
tween 12 (Kamal et al., 2020) and 60 (Cairo et al., 2017). The mean
follow-­up was 11.71 ± 11.29 months with a minimum of 4 months
(Hutton et al., 2018) and a maximum of 36 months (Thoma et al.,
2020). During the evaluation period, there were five drop-­outs
due to loss to follow-­up (Cairo et al., 2017; Thoma et al., 2020),
resulting in a final sample of 192 patients. Demographic data were
reported in all studies and are described in Table 2b. Smokers were
included in three studies (Cairo et al., 2017; Puzio et al., 2018;
Thoma et al., 2020).
Site and implant characteristics
Regarding mucosal phenotype, three studies only included sites with
a thin soft tissue phenotype (Hutton et al., 2018; Kamal et al., 2020;
Ustaoğlu et al., 2020), while two also included sites with a thick soft tis-
sue phenotype (Frizzera et al., 2019; Puzio et al., 2018) and the remain-
ing three did not report the phenotype. Several implant systems were
employed and only one study specified implant diameter (Frizzera et al.,
2019). The majority of the studies focused on the anterior region, either
only on the maxillary (Frizzera et al., 2019; Kamal et al., 2020) or on
both the maxillary and the mandibular anterior teeth (Puzio et al., 2018;
Schmitt et al., 2020; Thoma et al., 2020; Ustaoğlu et al., 2020; Table 2b).
Surgical interventions and provisionalization
Implants were usually placed following a delayed protocol, but in
two studies early (Schmitt et al., 2020) or immediate (Frizzera et al.,
|
      85
2019) implant placement was performed. Hard tissue conditions at
the time of implant placement varied greatly between studies. While
some of them excluded sites with insufficient bone availability
(Hutton et al., 2018; Kamal et al., 2020; Ustaoğlu et al., 2020), oth-
ers included bone defects and performed guided bone regeneration
at the time of implant placement (Frizzera et al., 2019; Puzio et al.,
2020; Schmitt et al., 2020). Soft tissue grafting was performed ei-
ther in the same surgical procedure (Frizzera et al., 2019; Hutton
et al., 2018; Kamal et al., 2020; Ustaoğlu et al., 2020) or at second-­
stage surgery (Cairo et al., 2017; Puzio et al., 2020; Schmitt et al.,
2020) or after implant placement but 3 months before the abutment
connection (Thoma et al., 2020).
In the experimental group, xenogeneic collagen matrix
(XCM) (Cairo et al., 2017; Frizzera et al., 2019; Puzio et al., 2018;
Schmitt et al., 2020; Thoma et al., 2020), allogenic dermal matrix
(Hutton et al., 2018), or platelet derivatives (Kamal et al., 2020;
Ustaoğlu et al., 2020) were used. The intervention was always made
with CTG obtained from the palate, an exception being one patient
in whom the tuberosity was selected as the donor site (Cairo et al.,
2017). Regarding the soft augmentation procedure, seven studies
raised a flap to position the graft and one prepared a buccal pouch,
avoiding trauma to the mesial and distal papilla (Frizzera et al.,
2019). Provisional implant-­supported restorations were placed im-
mediately in one study (Frizzera et al., 2019) and after 1–­3 months
of healing in two studies (Cairo et al., 2017; Schmitt et al., 2020).
3.6  |  Effects of intervention
The main results of the included studies are shown in Table 3b.
3.6.1  |  Primary outcome: STT changes
Methodology of assessment
Peri-­implant STT was assessed either by transmucosal probing
[i.e., using a needle (Cairo et al., 2017; Kamal et al., 2020), periodon-
tal probe (Hutton et al., 2018), or endodontic file (Thoma et al., 2020;
Ustaoğlu et al., 2020)] or using software to match scanned casts
(Schmitt et al., 2020). As mentioned above, Frizzera et al. (2019) and
Puzio et al. (2018) analyzed changes in STT by means of CBCT and
ultrasonography, respectively.
Synthesis of the results
Again, all studies were considered for the meta-­analysis and
publications providing the most complete data (Puzio et al., 2018)
or the longest follow-­
up (Thoma et al., 2020) were selected.
Meta-­
analysis showed a statistically significant gain in STT in
the CTG group when compared to soft tissue substitutes (n  = 8;
WMD  =  0.51  mm; 95% CI [0.28; 0.75]; 95% PI [−0.09; 1.12];
p  < .001), and there was moderate heterogeneity (I2  = 50.10%;
T2 = 0.05) (Figure 4).
86     | VALLES et al.

When considering the timing of soft tissue grafting and the
implant placement protocol, no statistically significant differences
were observed between subgroups with respect to changes in STT.
In contrast, statistically significant differences in STT changes were
found when considering the follow-­up as a subgroup (Table 4b), with
greater mean differences between CTG and substitutes in the long-­
term (≥ 1-­year follow-­up) compared to short-­term (<1 year).
Publication bias
No publication bias was observed for this outcome (t  = 0.05;
p  = 1) and the leave-­one-­out sensitivity analysis showed that the
exclusion of a single study did not alter any result.
3.6.2  |  Secondary outcomes
Volumetric changes
Volumetric analysis was conducted in two studies that evalu-
ated the efficacy of XCM in comparison to CTG (Schmitt et al.,
2020; Thoma et al., 2020). Different scales were used to pre-
sent the results of these two studies and meta-­
analysis using
SMD was performed to combine them. The meta-­
analysis did
not show statistically significant differences between the groups
(n  = 2; SMD =  0.61; 95% CI [−0.14; 1.36]; 95% PI [NE]; p  = .11)
(I2 = 15.85%; T2 = 0.05).

TA B L E 3 A  Outcomes of the selected studies comparing connective tissue graft and no graft

Mucosal thickness (mm) KM (mm)

Baseline Final Final-­Baseline Baseline

References Mean (SD) Mean (SD) Mean (SD) Mean (SD)

Frizzera et al., (2019) NSTG: 1 (0.18) NSTG: 2.11 (0.6)

CTG: 0.98 (0.29) CTG: 3.04 (0.61)
Hosseini et al., (2020) NSTG
1 mm: −0.68 (0.96);
3 mm: −0.46 (1.01)
CTG
1 mm: −0.04 (1.03);
3 mm: −0.16 (0.77)
Jiang et al., (2020) NSTG CTG
1 mm: −1.07 (0.45) 1 mm: −0.89 (0.48)
2 mm: −1.12 (0.52) 2 mm: −0.78 (0.48)
3 mm: −1.07 (0.62) 3 mm: −0.54 (0.59)
4 mm: −1.03 (0.75) 4 mm: −0.30 (0.66)
5 mm: −0.99 (0.82) 5 mm: −0.18 (0.74)
Migliorati et al., (2015) NSTG: 1.2 (0.5) NSTG: 1 (0.5) NSTG: 4.3 (1.1)
CTG 1.1 (0.6) CTG 1.5 (0.8) CTG: 3.3 (1.2)
Papapetros et al., (2019) Buccally Buccally
NSTG NSTG
0 mm: 2.58 (0.75); 0 mm: 1.54 (0.86);
2 mm: 2.61 (1); 2 mm: 1.93 (1.09);
4 mm: 2.45 (1.13) 4 mm: 2.10 (1.16)
CTG CTG
0 mm: 3.02 (1.33); 0 mm: 2.76 (1.25);
2 mm: 3.07 (1.26); 2 mm: 2.78 (1);
4 mm: 2.70 (1.48) 4 mm: 2.66 (1.02)
Puzio et al., (2018) NSTG NSTG NSTG
CEJ: 1.39 (0.65); CEJ: 2.1 (0.7); CEJ: 0.7 (0.8);
MGJ: 1.10 (0.44) MGJ: 1.46 (0.34) MGJ: 0.35 (0.6)
CTG CTG CTG
CEJ: 1.15 (0.4); CEJ: 2.68 (0.96); CEJ: 1.52 (1);
MGJ: 0.90 (0.3) MGJ: 2.05 (0.56) MGJ: 1.15 (0.5)
Puzio et al., (2020)

van Nimwegen et al., NSTG: −0.49 (0.54)

(2018) CTG: −0.68 (0.59)
Wiesner et al., (2010) NSTG: 2.05 (0.5) NSTG: 1.9 (0.32) NSTG: −0.15 (0.34)
CTG: 2 (0.47) CTG: 3.2 (0.42) CTG: 1.2 (0.63)

Note: CEJ, cemento-­enamel junction; CTG, connective tissue graft; KM, keratinized mucosa; MBL, marginal bone level; MGJ, mucogingival junction;
NSTG, no soft tissue graft; PES, Pink Esthetic Score; SD, standard deviation.
a
PES described by Fürhauser et al. (2005).
VALLES et al. |
      87

Again, neither of the investigations evaluated the volumetric
shrinkage over time.
Marginal bone level changes
Five studies analyzed MBL changes on periapical x-­rays using the
parallel technique (Cairo et al., 2017; Kamal et al., 2020; Puzio et al.,
2020; Thoma et al., 2020; Ustaoğlu et al., 2020), but only one in-
vestigation used individualized devices to ensure standardization
of radiographic images (Kamal et al., 2020). The meta-­
analysis
did not reveal statistically significant differences in radiographic
MBL changes between CTG and soft tissue substitutes (n  = 4;
WMD  =  0.10  mm; 95% CI [−0.02; 0.23]; 95% PI [−0.18; 0.38];
p = .11) (I2 = 0%; T2 = 0).
Moreover, as mentioned above, Frizzera et al. (2019) evaluated
the vertical resorption of the buccal plate and found no statistically
significant differences between CTG and soft tissue substitutes.
Clinical parameters for the diagnosis of peri-­implant health
When comparing CTG to soft tissue substitutes, changes in
PPD, plaque scores, and bleeding on probing were evaluated in
one study (Thoma et al., 2020), and another study only reported
final values (Cairo et al., 2017). The authors did not observe

MBL (mm) Recession (mm) PESa

Final Final-­Baseline Baseline Final Final-­Baseline

Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)

NSTG: 0.72 (0.57) NSTG: 9.87 (1.64)

CTG: −0.04 (0.3) CTG: 10.75 (1.38)
NSTG: 5.43 (1.9) NSTG: 0.5 (1.31) NSTG: 0.12 (0.33) NSTG: −0.16 (0.53)
CTG: 5.34 (1.7) CTG: 1.75 (0.35) CTG: 0.11 (0.45) CTG: −0.71 (0.39)
(1–­5  years)

NSTG: 0.26 (0.54)

CTG: 0.16 (0.6)

NSTG: 3.6 (1.2) NSTG: −0.01 (0.05) NSTG: −0.17 (0.06)

CTG: 2.9 (1.2) CTG: 0.03 (0.06) CTG: −0.06 (0.09)
CTG: −0.14 CTG
NSTG: −0.31 Distal: 0.73
Mesial: 0.80
NSTG
Distal: 0.66
Mesial: 1.06

NSTG: 0.31 (0.5)

CTG: 0.5 (0.58)
NSTG: −0.48 (1.13) NSTG: 11.36 (1.65)
CTG: 0.2 (0.7) CTG: 11.28 (1.67)
NSTG 0.44 (0.16) NSTG: 1.06 (0.41) NSTG: 0.62 (0.38) NSTG: 8.45 (1.46)
CTG: 0.35 (0.24) CTG: 1.14 (0.29) CTG: 0.79 (0.3) CTG: 11.32 (1.63)
88     | VALLES et al.

TA B L E 3 B  Outcomes of the selected studies comparing connective tissue graft and soft tissue substitutes

Mucosal thickness (mm) KM (mm)

Baseline Final Final-­Baseline Baseline Final Final-­Baseline

References Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)

Cairo et al., CM: 2.1 (0.6) CM: 3 (0.7) CM: 0.9 (0,2) CM: 3.1 (1.2) CM: 4.3 (1.2) CM: 1.1 (0.8)
(2017) CTG: 2.1 (0.6) CTG: 3.4 (0.6) CTG: 1.2 (0.3) CTG: 3.5 (1.7) CTG: 4.4 (1.5) CTG: 0.9 (0.8)
Frizzera et al. CM:0.98 (0.21) CM:2.1 (0.54)
(2019) CTG: 0.98 (0.29) CTG: 3.04 (0.61)
Hutton et al. ADM ADM ADM ADM: 4.95 (1.38) ADM: 4.5 (0.94) ADM: −0.45 (1.3)
(2018) 1 mm: 2.85 (1.40); 1 mm: 2.90 (1.24); 1 mm: 0.05 (1.57); CTG: 5.3 (1.16) CTG: 4.45 (1.14) CTG: −0.85 (1.13)
3 mm: 2.40 (1.02); 3 mm: 3.25 (1.30); 3 mm: 0.85 (1.29);
5 mm: 1.70 (0.67) 5 mm: 3.15 (0.94) 5 mm: 1.45 (1.17)
CTG CTG CTG
1 mm: 3.05 (1.28); 1 mm: 3.61 (1.11); 1 mm: 0.44 (2.04);
3 mm: 2.95 (1.17); 3 mm: 4.15 (1.33); 3 mm: 1.20 (1.48);
5 mm: 1.65 (0.75) 5 mm: 2.85 (0.58) 5 mm: 1.20 (0.89)
Kamal et al. PRF: 1.1 (0.36) PRF: 2.13 (0.46) PRF: 3.97 (0.85) PRF 3.67 (1.21)
(2020) CTG: 1.12 (0.22) CTG: 3.07 (0.65) CTG: 4.17 (1.17) CTG: 4.27 (1.16)
Puzio et al. CM CM CM
(2018) CEJ: 1.21 (0.49); CEJ: 2.10 (0.50); CEJ: 0.89 (0.6)
MGJ: 1.01 (0.41) MGJ: 1.57 (0.52) MGJ: 0.57 (0.6)
CTG CTG CTG
CEJ: 1.15 (0.4); CEJ: 2.68 (0.96); CEJ: 1.52 (1)
MGJ: 0.90 (0.3) MGJ: 2.05 (0.56) MGJ: 1.15 (0.5)
Puzio et al.
(2020)
Schmitt et al. CM: 0.3 (0.16)
(2020) CTG: 0.8 (0.61)
Thoma et al. CM: 3.2 (0.8) CM: 3.6 (1.5) CM: 0.44 (1.1) CM: 2.4 (0.8) CM: 2.5 (1.4) CM: 0.1 (0.8)
(2020) CTG: 2.7 (0.4) CTG: 3.8 (1.5) CTG: 1.1 (1.5) CTG: 3.2 (1.4) CTG: 3.2 (1) CTG: 0.1 (1.3)
Ustaoğlu et al. T-­PRF T-­PRF T-­PRF: 3.12 (0.6) T-­PRF: 3.21 (0.47)
(2020) OAC: 2.24 (0.51); OAC: 2.62 (0.57); CTG: 3.56 (1.07) CTG: 3.83 (0.91)
MBML: 1.89 (0.46); MBML: 2.36 (0.49);
MGJ1: 1.42 (0.35) MGJ1: 1.88 (0.29)
CTG CTG
OAC: 2.35 (0.58); OAC: 2.93 (0.64);
MBML: 2.16 (0.58); MBML: 2.82 0.75);
MGJ1: 1.52 (0.38) MGJ1: 2.20 (0.42)

ADM, acellular dermal matrix; CEJ, cemento-­enamel junction; CM, collagen matrix; CTG, connective tissue graft; KM, keratinized mucosa; MBL,
marginal bone level;
MBML, midbuccal mucosal level; MGJ, mucogingival junction; MGJ1, 1 mm above mucogingival junction; OAC, occlusal part of the alveolar crest;
PES, Pink Esthetic Score; PRF, platelet rich fibrin; SD, standard deviation; T-­PRF, titanium-­prepared platelet rich fibrin.
a
PES described by Fürhauser et al. (2005).

statistically significant differences; however, no meta-­

a nalysis
was performed.
Changes in the position of peri-­implant soft tissues
Two studies clinically evaluated the changes in the level of the soft
tissue margin by means of the clinical crown height (Thoma et al.,
2020) and the vertical distance between the implant shoulder and
the margin of the restoration (Cairo et al., 2017). As mentioned
above, Frizzera et al. (2019) analyzed clinical pictures with software.
When comparisons were made between autogenous graft and soft
tissue substitutes, the meta-­analysis showed significant differences
(n = 2; WMD = 0.50 mm; 95% CI [0.10; 0.89]; 95% PI [NE]; p = .014)
(I2 = 42.06%; T2 = 0.04), favoring the CTG group.
Regarding the position of the interproximal tissue, only two
studies comparing CTG with soft tissue substitutes assessed
changes in mesial and distal papillary length (Frizzera et al., 2019;
Thoma et al., 2020). While the study by Frizzera et al. (2019) showed
a slight decrease in both groups for mesial (CTG: 0.56 ± 0.57 mm;
XCM: 0.41 ± 0.7 mm) and distal (CTG: 0.47 ± 0.53 mm; XCM:
0.52 ± 0.67 mm) papilla height, only minor changes were observed
VALLES et al. |
      89

MBL (mm) Recession (mm) PESa

Baseline Final Final-­Baseline

Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)

CM: 0.7 (0.2) CM: −0.2 (0.4) CM: 0.04 (0.2)

CTG: 0.8 (0.3) CTG: −0.2 (0.4) CTG: 0 (0)
CM: 0.42 (0.6) CM: 10 (1.3)
CTG: −0.04 (0.3) CTG: 10.75 (1.38)

PRF: 0.51 (0.07) PRF: 2.06 (0.14) PRF: 1.55 (0.15) PRF: 11.33 (0.52)
CTG: 0.58 (0.16) CTG: 2.28 (0.28) CTG: 1.7 (0.2) CTG: 12.5 (1.05)

CM: 0.33 (0.62)

CTG: 0.5 (0.58)

CM: 0.4 (0.5) CM: −0.5 (1) CM: −0.9 (1) CM: 0.63 (0.88) CM: 9.1 (2.4)
CTG: −0.1 (0.3) CTG: −0.4 (0.3) CTG: −0.3 (0.3) CTG: 0 (0.66) CTG: 10 (2.3)

in the study by Thoma et al. (2020). However, due to the differ-
ent methodology used in these studies, a meta-­analysis could not
be performed. Moreover, Thoma et al. (2020) assessed the papilla
index described by Jemt (1997) and, again, no statistically sig-
nificant differences were observed between the two treatment
modalities.
The KM was assessed in five (Cairo et al., 2017; Hutton et al., 2018;
Kamal et al., 2020; Thoma et al., 2020; Ustaoğlu et al., 2020) studies
evaluating the efficacy of soft tissue substitutes. The meta-­analysis
revealed no significant differences in changes in the KM when com-
paring CTG to soft tissue substitutes (n = 5; WMD = −0.09 mm; 95%
CI [−0.40; 0.22]; 95% PI [−0.60; 0.41]; p = .57) (I2 = 0%; T2 = 0).
Esthetic outcomes
With respect to professional-­reported esthetic outcomes, only the
PES was used to perform the esthetic assessment (Frizzera et al.,
2019; Kamal et al., 2020; Thoma et al., 2020). Meta-­analysis demon-
strated that CTG resulted in significantly higher PES scores as com-
pared with soft tissue substitutes (n = 3; WMD = 1.02; 95% CI [0.29;
1.74]; 95% PI [−3.67; 5.70]; p = .01) (I2 = 0%; T2 = 0).
Furthermore, patient-­reported outcomes regarding esthetics
were evaluated at the final examination in one study that com-
pared XCM and CTG by means of a Visual Analog Scale (VAS) (Cairo
et al., 2017). The results showed that patients were satisfied with
esthetic outcomes, without statistically significant differences
 |
90      VALLES et al.
F I G U R E 2  Forest plot for soft tissue thickness meta-­analysis for studies comparing no graft and connective tissue graft
between the groups (90 ± 8 and 90 ± 9 for XCM and CTG group,
respectively).
Surgical time
Two studies compared surgical time when performing a soft tis-
sue augmentation procedure with either CTG or soft tissue sub-
stitutes (Cairo et al., 2017; Thoma et al., 2016). The meta-­analysis
failed to reveal a statistically significant reduction in duration of
the surgical procedure when using soft tissue substitutes (n  = 2;
WMD  =  5.54  min; 95% CI [−17.56; 28.65]; 95% PI [NE]; p  = .64)
(I2 = 88.25%; T2 = 247.85).
Patient-­related outcomes
Addressing the efficacy of soft tissue substitutes, only one study
assessed pain perception during the surgical procedure (Cairo et al.,
2017). The results showed statistically significant differences be-
tween both CTG and XCM groups (CTG: 35 ± 23; XCM: 17 ± 13).
On the other hand, three studies used a VAS to evaluate the pain
perceived by patients at 7–­10 days (Thoma et al., 2016), 7 days (Cairo
et al., 2017), and 14 days (Hutton et al., 2018) following soft tissue
thickening. A further study employed a Visual Rating Scale (i.e., mild,
moderate, and severe pain) for this purpose, though the data could
not be used owing to the use of the different scale (Kamal et al.,
2020) (Table 5). The results of the meta-­analysis failed to demon-
strate statistically significant differences between the groups (n = 3;
WMD  =  12.13; 95% CI [−2.88; 27.15]; 95% PI [−183.23; 197.49];
p  = .11) (I2  = 94.06%; T2  = 154.15). Moreover, patients from the
CTG group reported a statistically significant higher intake of anti-­
inflammatory tablets than the XCM group (n = 2; WMD = 1.68; 95%
CI [1.30; 2.07]; 95% PI [NE]; p < .001) (I2 = 0%; T2 = 0).
Finally, patient satisfaction was reported in four studies by
means of a VAS (Cairo et al., 2017; Hutton et al., 2018), a patient
satisfaction questionnaire (Kamal et al., 2020), or OHIP-­G14 (Thoma
et al., 2020) (Table 5). As different methodologies were used, only
two studies were included in the meta-­analysis and, again, no sta-
tistically significant differences were observed between the two
groups (n  = 2; WMD =  −0.49; 95% CI [−7.82; 6.85]; 95% PI [NE];
p = 0.90) (I2 = 80.36%; T2 = 22.60).
3.7  |  Quality assessment of the included studies
Only three studies were considered at low risk of bias (Cairo et al.,
2017; Hutton et al., 2018; Puzio et al., 2018) and four studies (Frizzera
et al., 2019; Kamal et al., 2020; Thoma et al., 2020; Ustaoğlu et al.,
2020) raised some concerns due to the randomization process, incom-
plete outcome data, or selection of the reported results (Figure 3b).
On the other hand, one CCT (Schmitt et al., 2020) was rated as “no
information” because of a lack of information on one criterion (i.e.,
measurement of the outcomes). In general, all the studies demon-
strated a low risk of bias in most domains (Figure 3b and Appendix S6).
The majority of the studies received either economic funding or
donation of biomaterials from the involved companies. One study
was self-­funded (Kamal et al., 2020) and one did not report the
source of funding (Ustaoğlu et al., 2020).
4  |  D I S C U S S I O N
4.1  |  Summary of primary and secondary outcomes
The present systematic review evaluated the efficacy of CTG,
as compared to the absence of a soft tissue grafting procedure
(FQ1) and use of soft tissue substitutes (FQ2), in terms of gain in
 VALLES et al.

TA B L E 4  Meta-­analysis for the soft tissue thickness comparing (a) connective tissue graft and no graft (b) connective tissue graft and soft tissue substitutes

Mean difference (MD) Heterogeneity

p-­value p-­value
Variable Subgroup N REML CI (95%) PI (95%) intra-­group inter-­group I2(%) p-­value

(a)
STT changes (mm) All 8 0.64 0.16, 1.13 −1.06, 2.35 .01 88.97 <.01
Type of implant placement 8
Immediate 4 0.73 −0.01, 1.46 −2.75, 4.21 .06 .73 93.50 <.01
Delayed 4 0.54 0.16, 1.13 −2.85, 3.92 .16 83.38 <.01
Timing of soft tissue grafting 8
At implant placement 6 0.76 0.22, 1.31 −1.30, 2.83 .01 .43 90.31 <.01
At 3 months after implant placement 2 0.21 −1.05, 1.45 NE .75 84.51 .01
Follow-­up 8
<1 year 2 0.96 −0.35, 2.28 NE .15 .55 89.13 <.01
≥1 year 6 0.54 0.01, 1.07 −1.31, 2.37 .05 88.89 <.01
(b)
STT changes (mm) All 8 0.51 0.28, 0.75 −0.09, 1.12 <.001 50.10 .07
Type of implant placement 8
Immediate 2 0.73 0.30, 1.16 NE <.01 .20 44.15 .18
Delayed 6 0.41 0.18, 0.64 −0.03, 0.82 <.01 31.09 .28
Timing of soft tissue grafting 8
At implant placement 4 0.61 0.17, 1.06 −1.17, 2.40 <.01 .32 58.99 .06
At 3 months after implant placement 4 0.37 0.19, 0.55 0.07, 0.60 <.01 13.52 .54
Follow-­up 8
<1 year 5 0.37 0.18, 0.55 −0.12, 0.87 <.01 .03 19.32 .26
≥1 year 3 0.79 0.46, 1.11 −1.29, 2.86 <.01 0 .61

Statistically significant p-­value < .05.

p-­value intra-­group: differences between (a) connective tissue graft and no graft, (b) connective tissue graft and soft tissue substitutes.
p-­value inter-­group: differences between subgroups.
Abbreviations: CI, confidence interval; NE, not estimable; PI, prediction interval; REML, restricted maximum likelihood; STT, soft tissue thickness.
|
      91
 |
92      VALLES et al.
peri-­implant STT and esthetic outcomes. The main outcomes de-
rived from this study were: (1) higher STT gain for CTG compared
to no graft or soft tissue substitutes; (2) no differences between
the groups in terms of changes in MBL or clinical parameters of
peri-­implant health; (3) less recession over time when using CTG
as compared to no graft or soft tissue substitutes; (4) no differ-
ences between any of the groups with regard to the position of the
interproximal tissue or changes in the KM; (5) higher PES scores for
CTG compared with soft tissue substitutes, but no difference as
compared with no soft tissue graft; and (6) no differences between
the groups with regard to PROMs, except for medication intake,
which was significantly higher when using CTG as compared to soft
tissue substitutes.
4.2  |  Agreements and disagreements with
previous findings
Regarding changes in STT, the results of the present meta-­analysis
have shown that mucosal augmentation with autogenous CTG re-
sults in significantly higher STT compared to no soft tissue graft
(WMD  = 0.64 mm; 95% CI [0.16;1.13]). Similarly, when compar-
ing mucosal augmentation between CTG and different types of
soft tissue substitute, in terms of STT, a WMD of 0.51 mm (95%
CI [0.28; 0.75]) in favor of the use of CTG was found. These find-
ings are in agreement with those published in recent systematic re-
views that compared CTG with no soft tissue augmentation (Atieh
& Alsabeeha, 2020) and soft tissue substitutes (Cairo et al., 2019;
Gargallo-­Albiol et al., 2019). When evaluating the efficacy of CTG,
Atieh and Alsabeeha (2020) demonstrated that immediate dental
implants in conjunction with CTG resulted in a significantly higher
F I G U R E 3  Risk of bias assessment of individual studies included in the research question (a) PICOS 1 (inter-­reviewer agreement = 91%;
kappa = 0.490; 95% CI [0.146; 0.835]; p < .001) and (b) PICOS 2 (inter-­reviewer agreement = 91.4%; kappa = 0.72; 95% CI [0.429; 1.011];
p < .001)
gain in STT compared to immediate implants without CTG (WMD:
0.87 mm). Other systematic reviews compared XCM and CTG with
respect to STT and also favored CTG over the use of soft tissue sub-
stitutes, with differences between groups ranging between 0.19 mm
(Gargallo-­Albiol et al., 2019) and 0.30 mm (Cairo et al., 2019).
It should be mentioned at this point that there was moderate
to high heterogeneity in results across the studies, which might be
partially explained by various discrepancies between the included
articles. Different methodologies and different measurements were
employed to evaluate STT. Some studies used transmucosal prob-
ing (i.e., by means of a needle, a periodontal probe, or endodontic
instruments), whereas others analyzed STT with ultrasonic devices
and CBCT scans or even on cast models, which limits the possibil-
ity of distinguishing between soft and hard tissues. Furthermore,
while some studies measured STT before the administration of local
anesthesia, others did so following the administration of the anes-
thetic. In this sense, absolute values of STT may have been over-
estimated since the anesthesia expands the soft tissue (Kobayashi
et al., 2020). Additionally, the fact that measurements were taken
at different vertical points could have influenced the results, since
less gain in STT was observed when the measurements were per-
formed 1 mm apical to the mucosal margin (at this level, wound de-
hiscences may be present and there is less vascular supply) (Hutton
et al., 2018; Jiang et al., 2020).
On the other hand, some investigations included small dehis-
cences (Migliorati et al., 2015; van Nimwegen et al., 2018) and buccal
defects (Frizzera et al., 2019). In this context, it can be assumed that,
if thin buccal bone walls are associated with greater changes in hard
and soft tissue dimensions (Chappuis et al., 2013), there will be an
increased risk of loss of volume if the buccal wall is already partially
or completely missing.
VALLES et al.
In the present study, the subgroup analysis failed to show sta-
tistically significant superior outcomes of CTG versus control (i.e.,
no graft) when the surgery was performed 3 months after implant
placement. In this context, in a systematic review, Lin et al. (2018)
evaluated the influence of timing of soft tissue grafting with au-
togenous CTGs and reported a mean STT gain of 1.12 mm (95% CI
[0.75;1.49]) and 0.95 mm (95% CI [0.58; 1.31]) with a simultaneous
and a staged soft tissue grafting approach, respectively; however,
these differences were not statistically significant. It should be
noted that, in the present investigation, the impact of soft tissue
grafting after the final restoration was not assessed since the graft
was placed before the definitive prosthetic rehabilitation in all of the
included studies. However, staged soft tissue augmentation pro-
cedures are more difficult to perform when the final restoration is
present (Thoma, Mühlemann, et al., 2014).
In addition, the long-­term stability of STT is of major importance
to ensure adequate esthetics and peri-­
implant health over time
(Esposito et al., 2012; Giannobile et al., 2018; Thoma et al., 2018).
The results of the present meta-­analysis showed that follow-­up (i.e.,
≥1 year or <1 year) did not influence the outcomes of STT changes
between CTG and the control group (no graft). In this respect,
Migliorati et al. (2015) and Hosseini et al. (2020) observed more soft
tissue shrinkage at control sites than at test sites after 2 and 5 years,
respectively. However, the present systematic review showed that
differences between CTG and soft tissue substitutes were affected
by follow-­up and that differences between groups were more pro-
nounced in those studies with ≥1 year of follow-­up, in favor of CTG.
Overall, although the evidence is scarce, it can be assumed that CTG
provides higher soft tissue stability than substitutes.
Optimal esthetic results are not always possible, since papillary
and mid-­facial recession may be present following implant therapy
(Cosyn et al., 2012). Some studies showed greater papilla fill when
soft tissue augmentation procedures were conducted at dental
implant sites (Thoma, Buranawat, et al., 2014) and, as mentioned
above, compared with thinner peri-­implant tissues, thicker tissues
have been reported to favor the appearance of the peri-­implant
papilla (Chow & Wang, 2010; Garabetyan et al., 2019). However,
only two studies reported on the height of the papilla and the results
should be interpreted with caution. When comparisons were made
between CTG and soft tissue substitutes, a meta-­analysis could not
be performed due to the different methodology used in the studies
conducted by Frizzera et al. (2019) and Thoma et al. (2020). Also,
it should be noted that Frizzera et al. (2019) included sites with a
buccal bone defect and did not exclude patients with periodontitis.
Certain risk factors for mucosal recession have been identified,
especially in immediately placed implants. These include a thin soft
tissue phenotype (Bittner et al., 2019), a facial malposition of the
implant (Evans & Chen, 2008), and a thin or damaged facial bone wall
at implant placement (i.e., 0.5 mm) (Yang et al., 2019). It should be
mentioned at this point that, in one study, 87% of anterior sites had
a mean width ≤1 mm (Huynh-­Ba et al., 2010) and that ridge preser-
vation procedures (Eghbali et al., 2018) or the use of a bone graft in
the gap between the implant fixture and the alveolar socket (G.-­H.
|
      93
Lin et al., 2014) certainly offered a benefit in maintaining the facial
bone and soft tissue level. In this context, a bone graft was placed in
those studies in which immediate (i.e., the gap was filled) or delayed
implants associated with buccal bone dehiscence were installed.
Furthermore, a flapless protocol and an immediate provisional res-
toration were considered when implants were immediately placed
(Frizzera et al., 2019; Jiang et al., 2020; Migliorati et al., 2015; van
Nimwegen et al., 2018) and, likewise, these two factors may lead
to a less mucosal recession (De Rouck et al., 2009; Lee et al., 2011).
The present study also demonstrated that soft tissue augmentation
with CTG resulted in significantly less recession than either no graft
(WMD  = 0.50 mm; 95% CI [0.19; 0.80]) or soft tissue substitutes
(WMD = 0.50 mm; 95% CI [0.10; 0.89]).
Interestingly, no statistically significant differences were found
between CTG and the absence of soft tissue augmentation with
respect to esthetic outcomes as assessed by means of the PES
(WMD  =  1.18; 95% CI [−0.56; 2.91]). At the last follow-­up, all in-
cluded studies reported a mean PES >8 in all study groups; thus, the
esthetic results were acceptable. However, Migliorati et al. (2015)
reported significantly lower PES scores in a thin soft tissue pheno-
type subgroup compared to a thick soft tissue phenotype subgroup.
Accordingly, soft tissue augmentation procedures around dental
implant sites should be considered to convert a thin soft tissue phe-
notype into a thicker one (Kan et al., 2010). In this regard, a recent
prospective study showed that, after 10 years of follow-­up, PES
scores remained stable in the presence of a thick mucosal pheno-
type (Seyssens et al., 2020). Nevertheless, in the present study, a
subgroup analysis could not be performed to explore the impact of
the mucosal phenotype on esthetic outcomes. On the contrary, the
use of CTG resulted in significantly higher PES scores compared to
soft tissue substitutes (WMD = 1.02; 95% CI [0.29; 1.74]).
The influence of soft tissue grafting procedures intended to
increase mucosal thickness on the gain in KM has seldom been
studied. This systematic review revealed that CTG did not mark-
edly increase the buccal width of KM compared to untreated sites
(WMD = 0.38 mm; CI 95% [−0.24; 0.98]; p = .23). This finding was
not surprising as dental implants are deprived of the periodon-
tal ligament—­
an essential structure that potentiates soft tissue
keratinization over the surrounding tissues (Karring et al., 1975).
Another possible explanation could relate to the quality charac-
teristics and the area of soft tissue harvesting. While almost all the
studies included in the review obtained the CTG from the palate,
Rojo et al. (2020) indicated that tuberosity CTG displayed more KT
gain (0.18 ± 0.53 mm) than CTG harvested from the lateral palate
(−0.42  ± 0.9 mm). Similarly, this systematic review suggested that
the use of soft tissue substitutes (i.e., XCM, ADM, or PRF) yielded
a comparable KM gain to CTG (WMD = −0.09 mm; CI 95% [−0.40;
0.22]; p  = .57). This fact could also be explained by the biological
integration of soft tissue substitutes with the adjacent tissues. Once
the blood clot has stabilized, ingrowth of vessels into the collagen
or acellular matrix subsequently leads to collagen fiber maturation
(Thoma et al., 2011). Similar findings with regard to KM width gain
after peri-­implant thickening were reported in a recent network
 |
94      VALLES et al.
F I G U R E 4  Forest plot for soft tissue thickness meta-­analysis for studies comparing connective tissue graft and soft tissue substitutes
meta-­analysis by Tavelli et al. (2020). Regardless of the soft tissue
graft used, mucosal thickening was not associated with a significant
gain in KM.
STT has been considered a factor that influences the peri-­
implant MBL changes (Valles et al., 2018). In this context, thickening
of the soft tissue profile has been associated with more stable inter-
proximal MBLs over time (Tavelli et al., 2020; Thoma et al., 2018).
However, the results of the present systematic review indicated
marginal bone resorption to be closely similar at sites with and sites
without CTG (WMD = −0.01 mm; CI 95% [−0.13;0.11]; p = .85). It
is likely that the use of soft tissue substitutes resulted in a similar
crestal bone alteration compared to CTG (WMD = 0.10 mm; CI 95%
[−0.02; 0.23]; p  = .11). This contradictory finding may be ascribed
to the impact of the surgical maneuvers associated with implant in-
stallation and soft tissue grafting on the crestal bone. Most of the
studies aimed to minimize alveolar resorption at the recipient site by
preparing a partial-­thickness flap (Cairo et al., 2017; Hosseini et al.,
2020; Migliorati et al., 2015; Puzio et al., 2020; Thoma et al., 2020;
Wiesner et al., 2010), though some used full-­thickness (Ustaoğlu
et al., 2020) or combined full-­partial thickness flaps (Kamal et al.,
2020; Papapetros et al., 2019).
It is also important to note that in some of the studies in-
cluded in the present systematic review, implant placement was
performed with buccal bone augmentation; this may have been a
source of potential bias affecting the applicability of the outcomes
since these studies did not report the effect of the bone regener-
ation on the dimensional changes and MBL. In this context, it has
been reported that the thickness of the buccal bone is significantly
correlated with the STT and the proximal crest width (Chappuis
et al., 2018).
As mentioned above, peri-­implant soft tissue grafting procedures
exert a notable impact on clinical and esthetic outcomes. However,
patient satisfaction with these procedures and perceptions of pain
should also be considered in daily practice and in scientific research.
Although few of the included studies provided data regarding pa-
tient satisfaction, the overall satisfaction scores in respect of soft
tissue reconstruction with CTG or soft tissue substitutes were con-
siderably high. However, the need for a second surgical site for har-
vesting the CTG was inevitably associated with increases in surgical
time, postsurgical discomfort, and medication intake. In accordance
with these considerations, CTG was associated with higher mor-
bidity (WMD =  12.13; 95% CI [−2.88; 27.15]), longer surgical time
(WMD = 5.54 min; 95% CI [−17.56; 28.65]), and higher intake of anti-­
inflammatory tablets (WMD = 1.68; 95% CI [1.30; 2.07]) compared
to soft tissue substitutes, though statistical significance was reached
only in the case of medication intake. These results are in line with
those of a recent meta-­analysis that found reductions in surgical
time, postsurgical discomfort, and painkiller consumption when
using XCM (Gargallo-­Albiol et al., 2019). However, the literature is
scarce in terms of PROMs.
4.3  |  Limitations of this systematic review and
recommendations for future research
This systematic review presents some limitations that should be con-
sidered. First, a small number of studies were included in the meta-­
analysis and there was high variability in the outcome measures. In
this context, measurements of STT (the primary outcome variable)
were taken at different reference points and an average was obtained
 VALLES et al.

TA B L E 5  Patient-­reported outcome measures: morbidity and patient satisfaction of studies comparing connective tissue graft and soft tissue substitutes.

Medication intake (number of pills during

Surgical time (minutes) Postsurgical pain the first week) Patient satisfaction

Soft tissue Soft tissue

substitutes CTG Soft tissue substitutes CTG Soft tissue substitutes CTG substitutes CTG

References Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)
a a a
Cairo et al. (2017) 35.5 (9.4) 51.7 (7) 13 (10) at day 7 37 (15) at day 7 2.2 (0.8) 3.9 (0.7) 95 (5) 91 (9)a
Frizzera et al. (2019)
Hutton et al. (2018) 2 weeks: 10.10 (7.8)a 2 weeks: 23.60 (24.7)a 94.8 (7.3)a 98.3 (2.3)a
4 weeks: 4.40 (4.3)a 4 weeks: 10.40 (16.5)a
8 weeks: 4.40 (8)a 8 weeks: 9.70 (15.5)a
16 weeks: 6.70 (9.5)a 16 weeks: 7.5 (15.5)a
Kamal et al. (2020) Day 0: 50% mild, 33.33% Day 0: 66.67% moderate
moderate and 16.67% and 33.33% severe;
severe; Day 7: no pain Day 7: no pain 16.67%,
83.33%, mild 16.67%b mild 83.33%b
Puzio et al. (2018)
Puzio et al. (2020)
Schmitt et al. (2020)
Thoma et al. (2016) 44.8 (19.7) 37.3 (12.2) −2.09 (0.24)a (change from −2.22 (0.24)a (change from 4 (3.5) 4.8 (3.5) 4.6 (5.9) at day 4.4 (5.6) at day
7 days to surgery) 7 days to surgery) 90 c 90 c
Thoma et al. (2020) 1.0 (1.3) at 0 (0) at 3 yearsc
3 yearsc
Ustaoğlu et al. (2020)

Note: SD, standard deviation

a
Results from a Visual Analogue Scale.
b
Results from a Verbal Rating Scale (Garcia et al., 2008).
c
Results from OHIP-­G14.
|
      95
 |
96      VALLES et al.
from each individual study to perform the meta-­analysis. Second, the
follow-­up of the included studies was short, and long-­term results (i.e.,
5 years) were provided by only one clinical controlled trial; however,
long-­term data are essential to evaluate the stability of the outcomes.
Third, the results could be biased since meta-­analyses were based
on implant-­and patient-­related data. Finally, patient-­related outcome
data were scarce, with high variation in selection and reporting. For
these reasons, there is a need for further long-­term studies with a
similar methodology and reference points focusing not only on clini-
cal but also on patient-­centered outcomes. Additionally, it would be
very interesting to evaluate the impact of mucosal phenotypes and
buccal bone thickness on the outcomes of these procedures.
In conclusion, the present systematic review and meta-­analysis,
while subject to certain limitations, shows that soft tissue augmen-
tation procedures are efficacious on soft tissue thickening. In partic-
ular, CTG is associated with:
• A significantly greater STT gain than is achieved with no graft or
with soft tissue substitutes.
• Significantly reduced recession compared with no graft or with
soft tissue substitutes.
• Significantly more favorable esthetic outcomes compared with
soft tissue substitutes.
• Significantly higher medication intake compared with soft tissue
substitutes.
4.4  |  Implications for clinical practice
According to the outcomes derived from this systematic review and
meta-­analysis, from a clinical perspective, soft tissue augmentation
by means of CTG may be indicated to increase soft tissue volume,
improve esthetic outcomes, and minimize the risk of mucosal reces-
sion over time. The use of soft tissue substitutes shows comparable
outcomes to CTG in terms of MBL changes, clinical parameters for
the diagnosis of peri-­implant health, and KM, as well as a reduction
in the consumption of medications.
AC K N OW L E D G M E N T S
The authors would like to thank all the authors who were contacted
to provide additional data and Antoni Parada for his help in the elec-
tronic search.
C O N FL I C T O F I N T E R E S T
The authors have stated explicitly that there is no conflict of interest
in connection with this article. The study was self-­funded.
AU T H O R C O N T R I B U T I O N S
CV, JV, and JN developed the protocol; CV and JV conducted the
research; LB, AP, and JN were asked for any difference related to
the search; CV and JV performed the data extraction and quality
assessment; CV, JV, LB, AP, and JN interpreted the results and wrote
the paper.
ORCID
Cristina Valles  https://orcid.org/0000-0002-2690-1208
Javi Vilarrasa  https://orcid.org/0000-0003-3494-1426
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