Clinical Oral Investigations

https://doi.org/10.1007/s00784-020-03683-w

ORIGINAL ARTICLE

Effect of cyanoacrylate tissue adhesive in postoperative palatal

pain management: a systematic review
Mario Escobar 1 & Patrícia Pauletto 2 & Cesar Augusto Magalhães Benfatti 1 & Ariadne Cristiane Cabral Cruz 1,3 &
Carlos Flores-Mir 4 & Bruno Alexandre Pacheco Castro Henriques 5

Received: 2 September 2020 / Accepted: 4 November 2020

# Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract
Objective To critically appraise available literature concerning the effect of cyanoacrylate tissue adhesive (CTA) in postoperative
palatal pain management.
Materials and methods Electronic databases (Cochrane, PubMed, LILACS, Scopus, and Web of Science) were searched,
complemented with grey literature databases up to June 2020. Studies reporting the effect of cyanoacrylate tissue adhesive
compared to any other methods in postoperative palatal pain management were considered eligible. The risk of bias among
and across included studies was assessed.
Results Finally, four studies were considered eligible. Regarding free gingival graft (FGG), cyanoacrylate tissue adhesive with
hemostatic sponge promoted less postoperative pain (PP) and analgesic consumption (AC). Also, cyanoacrylate tissue adhesive
with platelet-rich fibrin produced less PP and more wound healing at the palatal area than cyanoacrylate tissue adhesive and wet
gauze. Additionally, cyanoacrylate tissue adhesive promoted less PP and AC than wet gauze and suture. Concerning connective
tissue graft (CTG), cyanoacrylate tissue adhesive, and suture produced similar PP, AC, and willingness for retreatment.
Conclusions Based on the low certainty level, cyanoacrylate tissue adhesive appears to promote less PP and AC than wet gauze
and suture regarding FGG. Additionally, cyanoacrylate tissue adhesive appears to increase the effect of hemostatic sponge,
contributing to the reduction of PP and AC. Regarding CTG, cyanoacrylate tissue adhesive appears to promote similar PP, AC,
and willingness for retreatment than the suture. Therefore, cyanoacrylate tissue adhesive has shown promising usefulness for PP
management in FGG, but not a clear benefit for CTG.
Clinical relevance The adoption of different agents for the protection of the palatal donor site following gingival harvesting
procedures may provide better comfort to the patient.

Supplementary Information The online version contains

supplementary material available at https://doi.org/10.1007/s00784-020-
03683-w.

* Ariadne Cristiane Cabral Cruz 1

Department of Dentistry, Center for Education and Research on
ariadne.cruz@ufsc.br Dental Implants, Federal University of Santa Catarina,
Florianópolis, Brazil
Mario Escobar
2
marioescobar23@me.com Department of Dentistry, Brazilian Centre for Evidence-Based
Research, Federal University of Santa Catarina, Florianópolis, Brazil
Patrícia Pauletto
patricia.pauletto.p@gmail.com 3
Laboratory of Applied Virology, Federal University of Santa
Cesar Augusto Magalhães Benfatti Catarina, Florianópolis, Brazil
cesarbenfatti@yahoo.com
4
Faculty of Medicine and Dentistry, Department of Dentistry,
Carlos Flores-Mir
University of Alberta, Edmonton, Alberta, Canada
cf1@ualberta.ca
5
Bruno Alexandre Pacheco Castro Henriques Ceramic and Composite Materials Research Group, Federal
bruno.henriques@ufsc.br University of Santa Catarina, Florianópolis, Brazil

Keywords Systematic review; Palatal gingival harvesting . Wound healing . Autografts
Introduction
Periodontal and peri-implant plastic surgeries are being
performed more frequently due to promising results
achieved through the use of different techniques and
by increasing aesthetic demands [1]. The most predict-
able results seem to occur with the use of free gingival
graft (FGG) and connective tissue graft (CTG) in peri-
odontal and peri-implant plastic surgeries. In several sit-
uations, epithelium and/or connective tissue is removed
from the palatal area [1, 2] to be used in other adjacent
areas. Frequently, the chief complaints of patients un-
dergoing these plastic surgeries are discomfort in the
palatal area [3].
Therefore, to accelerate the healing process and to
reduce the discomfort and the delayed bleeding caused
by the palatal wound after FGG or CTG harvesting,
materials such as hemostatic agents, medicinal plant ex-
tract, and platelet concentrate have been used [4–9].
Recently, bio-adhesive materials, such as cyanoacrylate
tissue adhesive, have been successfully introduced in
dentistry as a way to prevent the formation of ischemic
areas resulting from sutures in periodontal aesthetic sur-
geries, as well as for wound closure in dermatology due
to their strong sealing, bacteriostatic, and hemostatic
properties [10, 11].
Moreover, cyanoacrylate tissue adhesive application
has been reported to reduce the postoperative morbidity
caused by FGG or CTG harvested technique due to the
proper protection of the palatal wound during the
healing. After the use, the adhesive film develops by
fast polymerization generated by hydroxyl groups on
the surfaces to be approximated. The exothermic reac-
tion of polymerization leads to strong and flexible
bonds [12]. Interestingly, water can act as a catalyst,
activating this anionic polymerization. Therefore, cyano-
acrylate tissue adhesive retains its adhesive qualities in
the presence of humidity. Additionally, bacteriostatic,
biodegradable, and hemostatic properties have been re-
lated to cyanoacrylate tissue adhesive [13].
Therefore, due to the hemostasis, tissue adhesion, and
bacteriostatic capacity of cyanoacrylate tissue adhesive,
the purpose of this systematic review (SR) was to critically
appraise available evidence to answer the following focused
question: “In patients who underwent surgical removal of
palatal tissue for graft purposes what is the effect of cyano-
acrylate tissue adhesive in comparison with other protection
methods regarding postoperative pain, consumption of an-
algesic, willingness for retreatment, and wound healing?”
Clin Oral Invest
Methods
Protocol and registration
The protocol of this SR is registered in the International
Prospective Register of Systematic Reviews (PROSPERO)
under the identification number CRD 42019135853. This
study was conducted according to the guidelines of the
Preferred Reporting Items for Systematic Reviews and
Meta-analysis checklist (PRISMA) [14].
Eligibility criteria
Inclusion criteria
The PICOS acronym (population, intervention, comparison,
outcome, and type of studies) was used to create the question
of this SR [15], where:
Patients (P): Patients who underwent surgical removal of
palatal tissue (connective and/or epithelized tissue graft).
Intervention (I): The protection of the palatal harvested area
was performed with cyanoacrylate tissue adhesive.
Comparison (C): The protection of the palatal harvested
area was performed with another method, such as suture,
platelet-rich fibrin, hemostatic agent, gauze compression, or
periodontal dressing material.
Outcome (O): Postoperative pain, consumption of analge-
sic, willingness for retreatment, and wound healing.
Studies were considered eligible when they met the follow-
ing inclusion criteria: Randomized clinical trials (RCTs) in-
volving patients of 18 years of age or older, no restriction on
ethnicity or gender, who underwent surgical removal of pala-
tal tissue for a graft, whose protection of the harvested area
was performed with cyanoacrylate tissue adhesive in the test
group, and another healing method in the control group. No
language or publication period restrictions were included.
Exclusion criteria
The exclusion criteria adopted were (1) studies that did not pres-
ent cyanoacrylate tissue adhesive intervention; (2) studies that
did not present a control group; (3) studies showing other tissue
donor sites than from the palatal area; (4) book chapters, guide-
lines, reviews, letters, conference, abstracts, case series, personal
opinions, animal studies, and technique description; (5) full study
copy not available; (6) duplicate data (e.g., dissertations/thesis in
which correspondent published articles were available).
Clin Oral Invest
Information sources
Keywords and MeSH terms were selected, and electronic
search strategies were conducted for the following databases:
Cochrane, LILACS (Latin American and Caribbean Health
Sciences), PubMed/MEDLINE, Scopus, and Web of
Science. Furthermore, an additional search in the grey litera-
ture (ProQuest Dissertations and Thesis, Google Scholar, and
OpenGrey databases), as well as a hand search of the included
studies references, was performed to ensure a trough screening
process. The search was carried out up to June 2020.
The software reference manager (Mendeley®, Elsevier,
London, UK) was used to collect references and remove du-
plicate. More information concerning appropriate truncation
and word combinations for each specific database is available
in Appendix 1.
Study selection
Two independent reviewers (M.E and P.P) selected the in-
cluded studies through screening, eligibility, and inclusion in
two phases. In phase 1, the reviewers independently assessed
title and abstract reading to identify potentially eligible studies
using online software (Rayyan, Qatar Computing Research
Institute) [16]. In phase 2, full texts of included studies were
screened. In case of disagreement, a third reviewer (C.B) was
consulted.
Data collection process
Two reviewers (M.E. and P.P) independently collected the
data. Any mistyping was further checked for accuracy by the
third reviewer (C.B). For the included studies, the following
information was collected: author, year of publication, coun-
try, sample size, mean age, interventions (test and control),
outcomes and evaluation method, statistical analysis, findings,
and principal conclusions. The authors of the included studies
were contacted if the required data were not complete.
Data items
The outcomes and evaluation method were:
Postoperative pain: to evaluate the postoperative pain, an
analogical visual scale (VAS) should have been used.
Consumption of analgesic: patients were asked about the
use of additional painkillers, in addition to those prescribed by
the surgeon.
Willingness for retreatment: patients were asked if they
would be willing to repeat the procedure, if necessary.
Wound healing score: the color of the palatal mucosa was
assessed by comparing it to the adjacent and opposite mucosa
side using the VAS scale (0−10).
Risk of bias in individual studies
The risk of bias (RoB) assessment of selected studies was
performed by two investigators (M.E. and P.P) independently.
All the studies were assessed using The Joanna Briggs
Institute Critical Appraisal Checklist for RCT [16].
Disagreements were solved by the third reviewer (C.B). The
possible answers to each of the RoB questions were “yes (Y),”
“no (N),” or “unclear (UN).” RoB was categorized as high
when the study reaches up to 49% score “yes,” moderate when
the study reached 50 to 69% score “yes,” and low when the
study reached more than 70% score “yes.”
Summary measures
Postoperative pain: measurements of VAS for each group
could be organized by mean (or median) and standard devia-
tions represented in numbers and/or percentages.
Consumption of analgesic: measurements of each group
could be expressed by mean (or median) and standard devia-
tions represented in numbers and/or percentages.
Willingness for retreatment: descriptive analysis with a di-
chotomous variable (yes/no).
Wound healing score: measurements for each group could
be performed by visual evaluation comparing the wound with
the contralateral counterpart using a visual analog scale
(VAS), clinical color photographs, epithelium chemical reac-
tion with hydrogen peroxide bubbling, and the presence of
fibrin or necrosis on the palatal wound, represented in num-
bers and/or percentages.
Synthesis of results
The synthesis of the results was described as narrative analy-
sis. First, a description per study was made and also a sum-
mary of the assessed outcome. To facilitate interpretation of
the results, the studies were divided into different harvesting
technique groups: (a) FGG and (b) CTG. Meta-analysis was
not justified due to clinical, methodological, and statistical
heterogeneity.
Certainty of evidence assessment
The Grading of Recommendations Assessment,
Development, and Evaluation (GRADE) evidence profile
was used to verify the overall certainty of the assessed evi-
dence [17]. Evidence was made based on these outcomes:
postoperative pain, consumption of analgesic, willingness
for retreatment, and wound healing score: a summary of find-
ings table was generated using online software (GRADE pro
GDT; the GRADE Working Group) (Table 3).

Results
Study selection
The first stage of the study selection process resulted in 1317
articles. Duplicate articles were removed, resulting in 1129
articles. A further 112 articles from the gray literature were
added, totaling 1241 articles. After phase 1 (title and abstract
reading), 30 potentially useful studies were included in phase
2 (full-text reading). Finally, after full-text reading, only four
Fig. 1 Flow diagram of literature search and selection criteria
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studies matched the inclusion criteria and were included for
further analysis in phase 2 (see Appendix 2). Fig. 1 shows a
flowchart describing the complete process of identification,
inclusion, and exclusion of studies.
Study characteristics
As expected, due to the selection criteria, all four studies in-
cluded in this SR are randomized controlled trials published
between 2017 and 2018. Two studies belonged to the same
Clin Oral Invest
author [8, 9] and were conducted in Germany. Two other
studies were conducted in Turkey [18] and Canada [7].
A total of 254 participants in all studies were included, with
an average age of 47.88 years. A maximum of 28 days and a
minimum of 24 h follow-up were evaluated at intervals of 1, 2,
3, 4, 5, 6, 7, 14, 21, and 28 days. More information concerning
study characteristics is provided in Table 1.
Risk of bias within studies
The RoB was assessed using the Joanna Briggs Institute’s
Critical Appraisal Checklist for the RCTs tool was considered
low for the four RCTs. The question related to the blinding
treatment of participants remained unclear in 3 studies [7, 8,
18] (Fig. 2). Further details about the RoB assessment is given
in Appendix 3.
Results of individual studies
FGG harvesting technique
Ozcan et al. [18] treated 141 patients in three different groups:
PRF (platelet-rich fibrin + cyanoacrylate tissue adhesive), BC
(cyanoacrylate tissue adhesive), and WG (wet gauze). The
immediate bleeding time (IBT) duration was 0.57 ± 0.15,
1.65 ± 0.69, and 3.18 ± 0.61 min for PRF, BC, and WG,
respectively (p = 0.001). While no delayed bleeding (DB)
was observed in PRF group throughout by 7 days postopera-
tive, most of BC group (34/42) demonstrated DB on the first
day and none after that. Conversely, patients from WG group
experienced DB throughout the first week (p = 0.0001).
Concerning sensibility, PRF demonstrated less sensibility
than WG (p = 0.0001), as well as BC, promoted less sensibil-
ity than WG (p < 0.05) at all time points, except at days 21 and
28, when most pain scores were zero for all groups.
Additionally, PRF demonstrated less sensibility than BC for
the first 5 days (p < 0.05), while no difference was detected
after day 6. Regarding healing, none group demonstrated
complete healing at week 1. BC and WG promoted similar
healing on week 2 (p = 0.106), while PRF showed better
results than WG on weeks 2 and 3 (p = 0.001). PRF
demonstrated better healing than BC at week 2 (p =
0.001), while no difference was observed at week 3 (p
= 0.314). Concerning feeding habits (FH), PRF demon-
strated better results than BC and WG at week 1 (p =
0.0001) and 2 (p = 0.05). At week 3, all groups dem-
onstrated similar FH (p = 0.417). Regarding pain per-
ception, PRF promoted less pain than WG (p < 0.001),
as well as BC, showed less pain than WG (p < 0.05) at
days 1, 2, 3, 4, 5, 6, 7, and 14. PRF also demonstrated
less pain than BC in the first 5 days (p < 0.05).
Concerning sensation, PRF demonstrated better results
than BC and WG at week 2 (p = 0.0001) and 3 (p =
0.0001), while similar sensation was reported for PRF
and BC at week 4 (p = 0.134). PRF suggested better
sensation than WG at week 4 (p < 0.05). Regarding
root coverage, all groups demonstrated similar results
(p > 0.05) at 6 months. The dimensions of the donor
site and graft tissue were similar for all groups (p >
0.05) (Table 2). Additionally, gender and age showed
no influence on VAS pain perception at all evaluated
time (p > 0.05).
Tavelli et al. [8] described 50 patients randomly distributed
in the following groups: suture only; suture + cyanoacrylate
tissue adhesive (PeriAcryl); suture + hemostatic sponge
(Spongostan); suture + periodontal dressing (Peripac); suture
+ hemostatic sponge + cyanoacrylate tissue adhesive
(Spongostan + PeryAcryl). Hemostasis was achieved in all
patients, regardless of the palatal wound protection method.
Participants who received only suture showed the highest pain
scores (p < 0.001), while suture + hemostatic sponge + cya-
noacrylate tissue adhesive reported the lowest VAS values
throughout the entire 2-week follow-up period (p > 0.05).
Concerning painkiller consumption, the lowest drug con-
sumption was reported for suture + hemostatic sponge + cya-
noacrylate. Sixty percent of patients from suture and 90% of
cyanoacrylate tissue adhesive, hemostatic sponge, and peri-
odontal dressing reported willingness to repeat the treatment,
while 100% of suture + hemostatic sponge + cyanoacrylate
tissue adhesive. Additionally, the lowest healing score was
awarded to suture (p < 0.001). Regarding pain (VAS) corre-
lated to age, it was observed an inverse correlation during
postoperative days 3 to 7 (– 0.03 VAS points per 10 years
on average, p < 0.05). Concerning graft dimensions, grafts
with more height demonstrated more pain perception 7 days
following the surgery (p < 0.05). Additionally, the graft di-
mensions were similar for all groups (p > 0.05) (Table 2).
Tavelli et al. [9] included 44 patients randomly distributed
into the following groups: suture + hemostatic sponge
(Spongostan); and suture + hemostatic sponge + cyanoacry-
late tissue adhesive (Spongostan + PeryAcryl). Concerning
patient pain perception, suture + hemostatic sponge + cyano-
acrylate tissue, adhesive promoted lower VAS values than
suture + hemostatic sponge on all evaluated days (p < 0.01).
Specifically, on day 7, suture + hemostatic sponge + cyano-
acrylate tissue adhesive suggested 1.8 lower VAS values than
suture + hemostatic sponge, while suture + hemostatic sponge
+ cyanoacrylate demonstrated 0.4 fewer values on day 14.
Regarding painkiller consumption, 2 patients from suture +
hemostatic sponge + cyanoacrylate tissue adhesive and 10
patients from suture + hemostatic sponge took 600 mg ibu-
profen (p < 0.01) for pain on the donor site. Concerning will-
ingness to repeat the treatment if necessary, 21 patients from
suture + hemostatic sponge + cyanoacrylate tissue adhesive
and 18 from suture + hemostatic sponge willing to retreatment
(p > 0.05). Also, regarding graft dimensions, grafts with less
Table 1 Summary of descriptive characteristics of included studies (n = 4)

Author (year) Group (n) Evaluated outcome Results Main

Country Mean age ± SD (years) conclusion
Type of study *Harvesting technique Evaluated Findings (p value)
Statistical analysis time

Ozcan et al. (2017) 1. PRF group (n = 42) Immediate and delayed Throughout IBT PRF: 0.57 ± 0.15 min PRF provided
Turkey 34.55 ± 7.64 bleeding: as reported by patient the study (p = 0.001) BC: 1.65 ± 0.69 min benefits for
RCT 2. BC group (n = 42) WG: 3.18 ± 0.61 min wound
Kolmogorov Smirnov 37.11 ± 4 DB PRF: no bleeding healing, pain,
3. WG group (n = 41) (p = 0.309) BC: day 1 and
37.61 ± 6.64 WG: day 1–7 medication
*FGG technique Sensibility: means of Week 2–3 Better results for PRF intake after
probing around donor area than BC and WG (p = 0.0001) FGG
Week 4 Similar findings for PRF and BC (p = 0.134) harvesting,
Better results for PRF than WG (p < 0.05) comparing to
Complete wound epithelialization Week 1 No CE in any group BC and WG.
(CE): using color photographs and H2O2 Week 2 85.7% CE for PRF
26.1% for BC
12.2% for WG
No significant difference
between BC and WG (p = 0.106)
Week 2–3 Better results for PRF than WG (p = 0.001)
Week 3 No significant difference
between PRF and BC (p = 0.314)
Feeding habits Week 1–2 Better results for PRF than BC
and WG groups (p < 0.05)
Week 3 Return to normal in all groups
Pain perception: (VAS) Day 1–14 Better results for PRF
compared to WG (p = 0.0001)
Day 1–14 Better results for BC compared to WG (p < 0.05)
Day 1–5 Better results for PRF compared to BC (p < 0.05)
Root coverage 6 months PRF 92.9%
BC 93.6%
WG 95.1%
Gender/age Throughout No influence VAS pain
the study perception at any time (p > 0.05)
Stravopolou et al. (2018) 1.Suture group Discomfort Week 1 No significant differences Cyanoacrylate
Canada (n = 18) between groups (p = 0.56) and suture
RCT 58.5 ± 13.52 Pain (VAS) Day 1 No significant differences performed
Wilcoxon rank sum test and Fisher exact 2. Cyanoacrylate between groups (p = 0.96) similarly
test group (n = 17) Week 1 No significant differences findings.
53.18 ± 20.2 between groups (p = 0.28) Moreover,
*CTG technique Self-analgesic intake Week 1 No significant differences the
between groups (p = 0.94) cyanoacry-
Suture group: 5 late
Cyanoacrylate group: 6 application
Application time (min) Throughout Better results for cyanoacrylate was about
the study than suture (p = 0.0001) 5 min faster
than suture,
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Table 1 (continued)

Author (year) Group (n) Evaluated outcome Results Main

Country Mean age ± SD (years) conclusion
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Type of study *Harvesting technique Evaluated Findings (p value)

Statistical analysis time

Modified-early wound Throughout No significant differences reducing the

healing index (MEHI) the study between groups (p = 0.91) total time of
Sex Throughout Groups were noticeably different the surgical
the study in their gender profiles (10 males 25 females) procedure.
Age, thickness of palate, length Throughout There were no major imbalances
of incision, thickness of graft, the study between the two wound closure methods
height of graft, or length of graft
Tavelli et al. (2018) 1. Suture group (n = 10) Immediate and Delayed bleeding: Throughout Hemostasis was achieved in all 50 patients, regardless In the protection
Germany 46.4 ± 14.4 as reported by patient the study of the palatal wound protection method of the palatal
RCT 2. Cyanoacrylate Palatal wound healing Throughout Optimal healing was associated with hemostatic agent wound,
Kruskal-Wallis or chi-square test to analyze + suture group the study + cyanoacrylate + suture group (p < 0.001) gelatin
characteristics across the treatment (n = 10) Throughout No palatal protection was lost prior to its removal (day sponge
groups 45.3 ± 11.5 the study 10) combined
3. Hemostatic agent Pain perception: (VAS) Day 1–14 Less pain for hemostatic agent + with
+ suture group cyanoacrylate + suture group than suture group cyanoacry-
(n = 10) (day 1–2 p = < 0.05) late was the
54.7 ± 10.3 (day 3–14 p = < 0.01) best option in
4. Periodontal dressing Better result for DLP group compared to the other test reducing
+ suture group (n = 10) groups (p > 0.05) pain and
52.8 ± 7.1 Painkillers Throughout 50% of participants from suture group reported taking postoperative
5. Hemostatic agent + the study additional doses of pain-relief medication discomfort.
cyanoacrylate+suture Throughout Agent + cyanoacrylate + suture group promoted the
group (n = 10) the study lowest drug consumption
50.9 ± 11.5 Willingness to repeat treatment Throughout Suture group 60%
*FGG technique the study Peripac + suture group 80%
Hemostatic agent + duture group 90%
Periodontal dressing + suture group 90%
Hemostatic agent + cyanoacrylate
+ suture group 100%
Correlations between postoperative pain and graft Throughout Age: − 0.03 VAS points per 10 years (younger
thickness, width, height, palatal thickness, and the study patients demonstrated less pain, p < 0.05)
age Throughout Graft width No correlation with pain
the study Graft thickness
Palatal thickness
Throughout Graft height 0.4 VAS per 1 mm (higher grafts
the study demonstrated more pain, p <
0.05)
Tavelli et al. 2019 1. Hemostatic sponge + suture Pain perception (VAS) Day 1–14 Less pain for hemostatic sponge + cyanoacrylate + Adding an
Germany group (n = 22) suture than hemostatic sponge + suture (p < 0.05) additional
RCT 52.6 ± 9.3 Analgesic consumption Day 1–14 Self-medication Hemostatic sponge + layer of
Student’s t test 2. Hemostatic sponge + (600 mg cyanoacrylate + suture: 2 cyanoacry-
ANOVA test cyanoacrylate + suture ibuprofen) Hemostatic sponge + suture: 10 late over a
group (n = 22) (p < 0.01) hemostatic
50.86 ± 12.55 Willingness for retreatment sponge on
Table 1 (continued)

Author (year) Group (n) Evaluated outcome Results Main

Country Mean age ± SD (years) conclusion
Type of study *Harvesting technique Evaluated Findings (p value)
Statistical analysis time

*FGG technique Throughout Hemostatic sponge + cyanoacrylate + suture: 21 the palatal

the study patients wound
Hemostatic sponge + suture:18 patients following
(p > 0.05) FGG
Full plaque score Throughout The FMPS and FMBS remained < 15% during the harvesting
the study study (p > 0.05) minimized
Graft size correlation with VAS scale Throughout Thickness of the Graft size correlation the
the study palate with VAS scale postoperative
Height of the graft discomfort
Width of the graft and the need
Thickness of the for
graft analgesics.
Graft size correlation with pain Throughout Graft width and thickness
the study showed no significant
differences (p > 0.05)
Day 3–14 Grafts with 14 mm width
or less promoted less pain
for both groups (p < 0.05).
Graft size between groups Throughout No significant difference
the study between groups (p > 0.05)

Note: PRF platelet rich fibrin, BC cyanoacrylate, WG wet gauze, IBT immediate bleeding time, DB delayed bleeding, CE complete epithelization, VAS visual analog scale, MEHI modified-early wound
healing index, HV high viscosity, FMPS full mouth plaque score, FMBS full mouth bleeding score. Note: mean age ± SD was expressed in years. All studies used n-butyl and 2-octyl cyanoacrylate tissue
adhesive (Periacryl HV, GluStitch, Delta, Canada)
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Clin Oral Invest
Fig. 2 Risk of bias - Joanna Briggs Institute Critical Appraisal Checklist for Randomized Clinical Trials
than 14 mm of width demonstrated less pain perception (p <
0.05) for both groups at days 3, 4, 6, 7, 10, and 14.
Furthermore, no correlation was observed between the
dimensions of the harvested graft and the VAS results
(p > 0.05) (Table 2).
CTG harvesting technique
Stavropoulou et al. [7] assessed data from 35 patients, accord-
ing to the groups: suture; and cyanoacrylate. Regarding the
level of discomfort from the palate at day 1, the mean value ±
standard deviation was 1.42 ± 1.88 and 1.27 ± 1.92 for suture
and cyanoacrylate, respectively, with no significant difference
(p = 0.96). During the first postoperative week, no significant
difference (p = 0.56) was also observed between the groups
(1.07 ± 1.87 and 1.55 ± 2.32 for suture and cyanoacrylate,
respectively). Concerning analgesic intake, similar results be-
tween groups were found (p = 0.94) since 5 patients from the
suture and 6 from the cyanoacrylate took analgesic. The au-
thors observed similar findings between cyanoacrylate and
suture regarding wound closure (p = 0.91). Concerning time
application, cyanoacrylate was faster than suture (2.16 ± 1.21
and 7.31 ± 2.19 min, respectively) (p < 0.0001). Additionally,
wound closure, analgesic intake, and postoperative pain per-
ception at week 1 was not correlated with the donor site or
graft dimensions (p > 0.05) (Table 2).
Synthesis of results
FGG harvesting technique
Postoperative pain All included studies regarding FGG eval-
uated postoperative pain [8, 9, 18]. In summary, use of cya-
noacrylate tissue adhesive when associated with hemostatic
sponge stabilized with suture promoted less postoperative pal-
atal pain (maximum VAS = 0.5) than hemostatic sponge sta-
bilized with suture (maximum VAS = 1.9) (p < 0.01) [8, 9],
and less postoperative pain than periodontal dressing and
suture (maximum VAS = 1.7), cyanoacrylate tissue adhesive
and suture (maximum VAS = 1.9), and suture alone (maxi-
mum VAS = 2.9) (p < 0.001) [8]. Additionally, cyanoacrylate
tissue adhesive with platelet-rich fibrin suggested less pain
(maximum VAS = 2.0) than cyanoacrylate alone (maximum
VAS=4.53) (p < 0.05), and wet gauze (maximum VAS =
6.10) (p < 0.001) [18]. It is relevant to mention that cyanoac-
rylate tissue adhesive alone (maximum VAS = 4.53) promot-
ed less pain than wet gauze (maximum VAS = 6.10) (p < 0.05)
[18], as well as, cyanoacrylate tissue adhesive associated with
suture (maximum VAS = 1.9) demonstrated less pain than
suture alone (maximum VAS = 2.9) (p < 0.01) [8].
Consumption of analgesic This outcome was addressed by
two studies [8, 9]. Both studies used cyanoacrylate associated
with suture. In summary, Tavelli et al. [8] demonstrate that
analgesic consumption was reduced for cyanoacrylate associ-
ated with hemostatic sponge stabilized with suture (2 pa-
tients), compared to hemostatic sponge secured with suture
(10 patients) (p < 0.01). Also, Tavelli et al. [9] demonstrate
that in cyanoacrylate associated with hemostatic sponge sta-
bilized with suture group, only 10% of patients consume ad-
ditional analgesic, versus 20% of cyanoacrylate and suture
group, 50% periodontal dressing and suture, 40% hemostatic
and suture, and 50% of suture alone group.
Willingness for retreatment Concerning the patient’s willing-
ness for retreatment, Tavelli et al. [8] observed similar find-
ings for cyanoacrylate tissue adhesive associated with hemo-
static sponge stabilized with suture (21 patients) and hemo-
static sponge secured with suture (18 patients) (p > 0.05).
Conversely, Tavelli et al. [9] demonstrated that 100% of pa-
tients showed willingness for retreatment for cyanoacrylate
tissue adhesive associated with hemostatic sponge stabilized
with suture versus 60% of patients for the suture group.
Wound healing According to this outcome addressed by two
studies [9, 18], cyanoacrylate tissue adhesive associated with a
Table 2 Summary of palatal mucosa and graft dimensions of included studies (n = 4)

Author, year Clinical dimensions Included groups/p value

PRF BC WG p value
(mean ± SD) (mean ± SD) (mean ± SD)
Ozcan et. al. 2017 Palatal mucosa thickness 4.0 ± 0.52 4.20 ± 0.54 4.21 ± 0.72 0.239
Palatal wound area 26.06 ± 1.67 26.34 ± 4.50 25.67 ± 1.53 0.578
Graft thickness 1.41 ± 0.13 1.42 ± 0.19 1.36 ± 0.14 0.125
Stravopolou et al. 2018 Sutures Cyanoacrylate
(mean ± SD) (mean ± SD)
Thickness palate 3.44 ± 0.77 3.38 ± 0.78
Length incision Thickness 18.94 ± 2.78 17.06 ± 5.51
Thickness graft 2.14 ± 0.36 2.41 ± 0.51
Height graft 7.03 ± 4.83 6.41 ± 2.67
Length graft 15.06 ± 4.26 13.76V± 6.42
Tavelli et al. (a) 2018 Spongostan (control) Cyanoacrylate (test) p value
(mean ± SD) (mean ± SD)
Graft height 4.63 ± 1.22 4.68 ± 0.84 > 0.05
Graft width 13.32 ± 4.32 13.87 ± 4.12 > 0.05
Graft thickness 1.59 ± 0.33 1.70 ± 0.3 > 0.05
Palatal thickness 4.27 ± 1.24 4.25 ± 0.84 > 0.05
Tavelli et al. (b) 2018 Suture (control) PeriAcryl Spongostan Peripac Spongostan + PeriAcryl p value
(mean ± SD) (mean ± SD) (mean ± SD) (mean ± SD) (mean ± SD)
Graft height 5±1 5.4 ± 1.8 5.2 ± 1.1 4.6 ± 1.6 4.9 ± 0.7 0.94
Graft width 18.2 ± 5 13.0 ± 4.9 14.8 ± 5.4 13.2 ± 4.5 11.9 ± 4.4 0.08
Graft thickness 1.6 ± 0.4 1.3 ± 0.4 1.8 ± 0.4 1.6 ± 0.4 1.7 ± 0.4 0.08

Note: PRF platelet rich fibrin, BC cyanoacrylate, WG wet gauze

Clin Oral Invest
Clin Oral Invest

hemostatic agent, such as platelet-rich fibrin (36 and 42) dem- to the small samples and different outcome analyses.
onstrated more sites of complete epithelialization than cyano- Further explanations concerning the evidence appraisal
acrylate (11 and 39) and wet gauze (5 and 19) at the second are presented in Table 3.
and third week, respectively [18]. Also, cyanoacrylate tissue
adhesive associated with hemostatic sponge and suture (9.0
±0.7) promoted better healing scores than a hemostatic sponge
with suture (6.8±1) (p<0.001) [9]. Discussion

Due to the predictable results concerning the use of FGG and

CTG harvesting technique
Postoperative pain Cyanoacrylate tissue adhesive alone (1.27
± 1.92 and 1.55 ± 2.32) or suture alone (1.42 ± 1.88 and 1.07 ±
1.87) promoted similar postoperative palatal pain at the first
day (p = 0.96) and first week (p = 0.28), respectively [7].
Consumption of analgesic Regarding the consumption of an-
algesic, similar findings were observed for cyanoacrylate tis-
sue adhesive alone (6 patients) or suture alone (5 patients)
(p>0.05) [7].
Wound healing Similar results were demonstrated for cyano-
acrylate (35.3%, 23.5%, and 41.2%) and suture (44.4%,
16.7%, and 38.9%) groups regarding the 3 levels of early
wound healing, respectively (p > 0.05) [7].
Certainty of evidence assessment
The certainty in cumulative evidence assessed by
GRADE was considered low for all outcomes. Overall,
for all the outcomes, the “risk of bias” topic was cate-
gorized as “not serious”, the “inconsistency” was con-
sidered “serious” due to the high methodological hetero-
geneity, mainly regarding different interventions in the
studies. The “indirectness” topic was deemed “not seri-
ous.” Also, “imprecision” was considered “serious” due
CTG in periodontal and peri-implant plastic surgeries, in sev-
eral clinical situations, epithelium, and/or connective tissue is
removed from the palatal area [1, 2]. Despite the promising
results regarding these plastic surgeries, most patients reported
discomfort in the wounded palatal area [2, 3, 19–22].
Therefore, to minimize this discomfort, accelerate the healing
process, and reduce delayed bleeding caused by the palatal
wound during FGG or CTG harvesting, some methods have
been proposed, including cyanoacrylate tissue adhesive.
Therefore, the purpose of this SR was to critically appraise
available literature concerning the effect of cyanoacrylate tis-
sue adhesive in postoperative palatal pain management.
In summary, regarding FGG, cyanoacrylate tissue adhesive
associated with hemostatic sponge stabilized with suture pro-
moted less postoperative palatal pain and analgesic consump-
tion than hemostatic sponge secured with suture, periodontal
dressing and suture, cyanoacrylate tissue adhesive and suture,
and suture alone. Also, cyanoacrylate tissue adhesive with
platelet-rich fibrin suggested less pain and more wound
healing at the palatal area than cyanoacrylate tissue adhesive
alone and wet gauze. Additionally, cyanoacrylate tissue adhe-
sive alone promoted less pain and analgesic consumption than
wet gauze, as well as cyanoacrylate tissue adhesive associated
with suture, demonstrated less pain and analgesic consump-
tion than suture alone. Concerning CTG, cyanoacrylate tissue
adhesive alone and suture alone promoted similar postopera-
tive palatal pain, analgesic consumption, and willingness for

Table 3 GRADE summary of findings

Certain of evidence Certain

№ of studies Outcome Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations

04 Postoperative pain RCT Not serious Seriousa Not serious Seriousb None ⨁⨁◯◯
Low
02 Consumption of analgesic RCT Not serious Seriousa Not serious Seriousb None ⨁⨁◯◯
Low
02 Willingness for retreatment RCT Not serious Seriousa Not serious Seriousb None ⨁⨁◯◯
Low
02 Wound healing score RCT Not serious Seriousa Not serious Seriousb None ⨁⨁◯◯
Low

Explanations
a
Different approaches between control groups, inability to do meta-analysis
b
The analysis changes according to the type of variable in some outcomes. Samples still small

retreatment. Therefore, we may affirm cyanoacrylate tissue
adhesive showed fair usefulness for pain management in
FGG but no meaningful difference for CTG.
Cyanoacrylate tissue adhesive has been applied intraorally
with different purposes due to its strong sealing, hemostatic,
and antimicrobial properties. Several studies that tested the
use of cyanoacrylate tissue adhesive as an alternative to sutur-
ing intraoral and extraoral wounds concluded that cyanoacry-
late tissue adhesive is faster to place, more reliable, prevent
ischemic zones caused by suture stitches, and enhance hemo-
stasis [11]. Moreover, despite cyanoacrylate tissue adhesive
did not improve the evaluated outcomes in CTG, the time
necessary to apply the bio-adhesive was shorter than the su-
ture method, [7].
Herein all the included studies used a blend of n-butyl
cyanoacrylate and 2-octyl cyanoacrylate. Cyanoacrylate tissue
adhesive sets within 5–10 s by polymerization in the presence
of humidity by saline solution and even blood. Longer-chain
derivatives such as ethyl-2-cyanoacrylate, isobutyl-2-cyano-
acrylate, butyl-2-cyanoacrylate, n-butyl cyanoacrylate, and
2-octyl-cyanoacrylate have been developed. Changing the
type of alkyl chains in the compound to one with a longer
molecular chain can reduce tissue toxicity [23]. Numerous
studies have been demonstrated that n-butyl cyanoacrylate
may be compared with any other wound closure devices, of-
fering additional benefits such as strength and flexible bind-
ing, which make it appropriate for wound closure, tissue bar-
rier capability, and short action time [24–27]. Additionally,
comparing the cost of cyanoacrylate tissue adhesive and con-
ventional sutures, a bottle containing 5 mL of cyanoacrylate
has an average cost of $ US 130 and can be used in 10 to 15
patients, while the average cost of nylon 5–0 conventional
sutures is $ US 40 per package. Therefore, although the cya-
noacrylate tissue adhesive may represent an additional cost, in
case it is added to the suture, this cost is not relevant.
Despite the cyanoacrylate tissue adhesive capacity to poly-
merize in the presence of humidity, the recommendation for
this bio-adhesive is that tissue surfaces should be cleaned and
dried as much as possible before its application. Probably, for
this reason, the included articles achieved hemostasis with
different materials before cyanoacrylate tissue adhesive appli-
cation to enhance and facilitate bio-adhesive useful time ad-
herence. Additionally, the mechanisms to reach hemostasis
used in the included articles were porcine-derived collagen
hemostatic absorbable sponge with suture for all groups [8];
sterile gauze for few seconds for all groups [9]; 15% ferric
sulfate solution applied by sterile gauze for 1 min with mod-
erate pressure for one group [7, 18]; platelet-rich fibrin
and wet gauze for one group [7, 18]; cyanoacrylate directly
applied without previous gauze pressure for one group [7, 18];
and suture alone for one group [7].
It is relevant to mention that careful application of cyano-
acrylate tissue adhesive drop by drop is recommended than
Clin Oral Invest
rapid massive application to promote the cyanoacrylate tissue
adhesive application on the entire wound and also minimize
waste of bio-adhesive [7–9, 18]. Also, limitations re-
garding the use of cyanoacrylate tissue adhesive have
been related to the incorrect application, food intake
after surgery that removes cyanoacrylate tissue adhesive
from the wounded palatal area, a rapid peel off, and
constant bleeding during the cyanoacrylate tissue adhe-
sive application that may jeopardize its adhesion.
In this SR, we reported that regarding FGG, cyanoacrylate
tissue adhesive promoted less pain and analgesic consumption
than wet gauze and suture. Also, cyanoacrylate tissue adhe-
sive increased the role of hemostatic sponge and platelet-rich
fibrin, contributing to the reduction of postoperative pain and
analgesic consumption. Platelet-rich fibrin membrane
used in several applications releases high amounts of
various growth factors, such as thrombospondin-1
(TSP-1) for at least 7 days, which eventually accelerates
the immune system, cell migration, and proliferation,
supporting hemostasis and wound healing [28, 29].
While the findings referring to FGG showed that cyanoac-
rylate tissue adhesive, combined with other materials or alone,
improved postoperative pain and decreased analgesic intake,
regarding CTG, cyanoacrylate tissue adhesive suggested no
benefits for the assessed outcomes. Probably, these findings
are because, in the CTG, there is the remaining epithe-
lium in the palatal donor area that allows healing by
primary intention, which reduces postoperative bleeding,
wound infection, and increase the protection of the sur-
gical wound compared to healing by secondary inten-
tion, as occurred in FGG harvesting technique [19].
Low RoB judgments indicate that none or minor method-
ological flaws occurred in the included studies. Therefore,
none or small deviations from the true effect estimation be-
fallen, providing confidence in the interpretation of the find-
ings [30]. Thus, with regards to the limitations of this SR,
some included studies used cyanoacrylate tissue adhesive as-
sociated with other materials, such as suture and platelet-rich
fibrin. Moreover, further studies shall be performed, compar-
ing only cyanoacrylate tissue adhesive with other materials.
Conclusions
Based on the low certainty level, cyanoacrylate tissue adhe-
sive seems to promote less postoperative pain and analgesic
consumption than wet gauze and suture regarding FGG.
Additionally, cyanoacrylate tissue adhesive appears to in-
crease the effect of hemostatic sponge, contributing to the
reduction of postoperative pain and analgesic consumption.
Concerning CTG, cyanoacrylate tissue adhesive seems to pro-
mote similar postoperative pain, analgesic consumption, and
willingness for retreatment than the suture.
Clin Oral Invest
Acknowledgments The authors thank Ms. Maria Gorete Manteguti Savi
for the instructions regarding the search strategy construction.
Authors’ contributions Mario Escobar, Patrícia Pauletto, Cesar Augusto
Magalhães Benfatti, Ariadne Cristiane Cabral Cruz, Carlos Flores-Mir,
and Bruno Alexandre Pacheco Castro Henriques contributed to the con-
ception and the design of the study; Mario Escobar, Patrícia Pauletto, and
Ariadne Cristiane Cabral Cruz collected the data; Mario Escobar, Patrícia
Pauletto, and Ariadne Cristiane Cabral Cruz analyzed the data; and Mario
Escobar, Patrícia Pauletto, Cesar Augusto Magalhães Benfatti, Ariadne
Cristiane Cabral Cruz, Carlos Flores-Mir, and Bruno Alexandre Pacheco
Castro Henriques drafted and critically revised the manuscript. All au-
thors read and approved the final manuscript.
Funding This study was not supporter by any funding.
Patrícia Pauletto is supported with scholarship by Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)
(Coordination for the Improvement of Higher Education Personnel),
Brazil.
Compliance with ethical standards
Conflict of interest Mario Escobar declares that he has no conflict of
interest. Patrícia Pauletto declares that she has no conflict of interest.
Cesar Augusto Magalhães Benfatti declares that he has no conflict of
interest. Ariadne Cristiane Cabral Cruz declares that she has no conflict
of interest. Carlos Flores-Mir declares that he has no conflict of interest.
Bruno Alexandre Pacheco Castro Henriques declares that he has no con-
flict of interest.
Ethical approval This article does not contain any studies with human
participants or animals performed by any of the authors.
Informed consent The formal consent is not required for this type of
study.
References
1. Cairo F (2017) Periodontal plastic surgery of gingival recessions at
single and multiple teeth. Periodontol 75(1):296–316. https://doi.
org/10.1111/prd.12186
2. Zucchelli G, Tavelli L, McGuire MK et al (2020) Autogenous soft
tissue grafting for periodontal and peri-implant plastic surgical re-
construction. J Periodontol 91(1):9–16. https://doi.org/10.1002/
JPER.19-0350
3. Zucchelli G, Mounssif I, Mazzotti C et al (2014) Does the dimen-
sion of the graft influence patient morbidity and root coverage out-
comes? A randomized controlled clinical trial. J Clin Periodontol
41(7):708–716. https://doi.org/10.1111/jcpe.12256
4. Keceli HG, Aylikci BU, Koseoglu S, Dolgun A (2015) Evaluation
of palatal donor site haemostasis and wound healing after free gin-
gival graft surgery. J Clin Periodontol 42(6):582–589. https://doi.
org/10.1111/jcpe.12404
5. Madi M, Kassem A (2018) Topical simvastatin gel as a novel ther-
apeutic modality for palatal donor site wound healing following
free gingival graft procedure. Acta Odontol Scand 76(3):212–219.
https://doi.org/10.1080/00016357.2017.1403648
6. Ozcan-Kucuk A, Alan H, Gul M, Yolcu U (2018) Evaluating the
effect of resveratrol on the healing of extraction sockets in cyclo-
sporine a–treated rats. J Oral Maxillofac Surg 76(7):1404–1413.
https://doi.org/10.1016/j.joms.2018.02.030
7. Stavropoulou C, Atout RN, Brownlee M et al (2019) A randomized
clinical trial of cyanoacrylate tissue adhesives in donor site of con-
nective tissue grafts. J Periodontol 90(6):608–615. https://doi.org/
10.1002/JPER.18-0475
8. Tavelli L, Asa’ad F, Acunzo R et al (2018) Minimizing patient
morbidity following palatal gingival harvesting: a randomized con-
trolled clinical study. Int J Periodontics Restorative Dent 38(6):
e127–e134. https://doi.org/10.11607/prd.3581
9. Tavelli L, Ravidà A, Saleh MHAA et al (2019) Pain perception
following epithelialized gingival graft harvesting: a randomized
clinical trial. Clin Oral Investig 23(1):459–468. https://doi.org/10.
1007/s00784-018-2455-5
10. Rossberg M, Dent M (2008) Long-term results of root coverage
with connective tissue in the envelope technique: a report of 20
cases. Int J Periodontics Restorative Dent 28(1):19–27
11. Nevins M, Mendoza-Azpur G, De Angelis N, Kim D (2018) The
biocompatibility of cyanoacrylate tissue adhesive in conjunction
with a collagen membrane for providing soft and hard tissue regen-
eration in extraction socket preservation procedures. Int J
Periodontics Restorative Dent 38s37–s42. https://doi.org/10.
11607/prd.3770
12. Singer AJ, Quinn JV, Hollander JE (2008) The cyanoacrylate top-
ical skin adhesives. Am J Emerg Med 26(4):490–496. https://doi.
org/10.1016/j.ajem.2007.05.015
13. Rewainy M, Osman S (2015) The use of N-butyl cyanoacrylate
adhesive in the closure of muco- periosteal flap after the surgical
extraction of impacted mandibular third molar. Alexandria Dent J
40(PeriAcryl 90):152–159
14. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred
reporting items for systematic reviews and meta-analyses: the
PRISMA statement. Ann Intern Med 151(4):264–269
15. Stone PW (2002) Popping the (PICO) question in research and
evidence-based practice. Appl Nurs Res 15(3):197–198. https://
doi.org/10.1053/apnr.2002.34181
16. Tufanaru C, Munn Z, Aromataris E et al (2017) Chapter 3:
Systematic reviews of effectiveness. In: Aromataris E, Munn Z
(eds). Joanna Briggs Institute Reviewer’s Manual. Joanna Briggs
Inst
17. Manheimer E (2012) Summary of findings tables: presenting the
main findings of cochrane complementary and alternative
medicine–related reviews in a transparent and simple tabular for-
mat. Glob Adv Health Med 1(1):90
18. Ozcan M, Ucak O, Alkaya B et al (2017) Effects of platelet-rich
fibrin on palatal wound healing after free gingival graft harvesting:
a comparative randomized controlled clinical trial. Int J
Periodontics Restorative Dent 37(5):e270–e278. https://doi.org/
10.11607/prd.3226
19. Zucchelli G, Mele M, Stefanini M et al (2010) Patient morbidity
and root coverage outcome after subepithelial connective tissue and
de-epithelialized grafts: a comparative randomized-controlled clin-
ical trial. J Clin Periodontol 37(8):728–738. https://doi.org/10.
1111/j.1600-051X.2010.01550.x
20. Gobbato L, Nart J, Bressan E et al (2016) Patient morbidity and root
coverage outcomes after the application of a subepithelial connec-
tive tissue graft in combination with a coronally advanced flap or
via a tunneling technique: a randomized controlled clinical trial.
Clin Oral Investig 20(8):2191–2202. https://doi.org/10.1007/
s00784-016-1721-7
21. Wyrębek B, Górski B, Górska R et al (2018) Patient morbidity at
the palatal donor site depending on gingival graft dimension. Dent
Med Probl 55(2):153–159. https://doi.org/10.17219/dmp/91406
22. Chiu T-S, Chou H-C, Kuo P-J et al (2020) A novel design of palatal
stent to reduce donor site morbidity in periodontal plastic surgery. J
Dent Sci 15(2):136–140. https://doi.org/10.1016/j.jds.2020.03.014

23. Leggat PA, Kedjarune U, Smith DR (2004) Toxicity of cyanoacry-
late adhesives and their occupational impacts for dental staff. Ind
Health 42(2):207–211. https://doi.org/10.2486/indhealth.42.207
24. Aksoy F, Yilmaz F, Yildirim YS et al (2010) Use of N-butyl cya-
noacrylate in nasal septoplasty: histopathological evaluation using
rabbit nasal septum model. J Laryngol Otol 124(7):753–758.
https://doi.org/10.1017/S0022215110000095
25. Eggers MD, Fang L, Lionberger DR (2011) A comparison of
wound closure techniques for total knee arthroplasty. J
Arthroplast 26(8):1251–1254. https://doi.org/10.1016/j.arth.2011.
02.029
26. Nguyen AJ, Baron TH, Burgart LJ et al (2002) 2-Octyl-
cyanoacrylate (Dermabond), a new glue for variceal injection ther-
apy: results of a preliminary animal study. Gastrointest Endosc
55(4):572–575. https://doi.org/10.1067/mge.2002.122032
27. Pérez M, Fernández I, Márquez D et al (2000) Use of N-butyl-2-
cyanoacrylate in oral surgery: biological and clinical evaluation.
Artif Organs 24(3):241–243. https://doi.org/10.1046/j.1525-1594.
2000.06519.x
Clin Oral Invest
28. Femminella B, Iaconi MC, Di Tullio M et al (2016) Clinical com-
parison of platelet-rich fibrin and a gelatin sponge in the manage-
ment of palatal wounds after epithelialized free gingival graft har-
vest: a randomized clinical trial. J Periodontol 87(2):103–113.
https://doi.org/10.1902/jop.2015.150198
29. Jain V, Triveni MG, Kumar ABT, Mehta DS (2012) Role of
platelet-rich-fibrin in enhancing palatal wound healing after free
graft. Contemp Clin Dent 3(Suppl 2):S240–S243. https://doi.org/
10.4103/0976-237X.101105
30. Guyatt GH, Oxman AD, Vist GE et al (2008) GRADE: an emerg-
ing consensus on rating quality of evidence and strength of recom-
mendations. BMJ 336(7650):924–926. https://doi.org/10.1136/
bmj.39489.470347.AD
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