Clinical Oral Investigations (2021) 25:6347–6356

https://doi.org/10.1007/s00784-021-03935-3

ORIGINAL ARTICLE

Clinical evaluation of the treatment of multiple gingival recessions

with connective tissue graft or concentrated growth factor using
tunnel technique: a randomized controlled clinical trial
Birsen Korkmaz 1 & Umut Balli 2

Received: 7 December 2020 / Accepted: 30 March 2021 / Published online: 8 April 2021
# The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

Abstract
Objective To assess the effectiveness of the combination of tunnel technique (TT) and concentrated growth factor (CGF) for root
coverage in treating multiple gingival recessions (GR) and compare with the connective tissue graft (CTG).
Materials and methods Forty patients with Miller Class I and II maxillary or mandibular GR were randomly divided into two
groups as follows: TT + CTG and TT + CGF. The results at baseline and 6 months were evaluated for the following clinical
parameters: complete root coverage (CRC), mean root coverage (MRC), gingival thickness (GT), gingival recession width (RW),
gingival recession depth (RD), and keratinized tissue width (KTW).
Results At 6 months, a statistically significant difference was found in RD, RW, MRC, CRC, KTW, and GT compared with the
baseline (p < 0.05). MRC was determined 89.52±16.36% in the TT + CTG and 76.60±24.10% in the TT + CGF (p < 0.05). CRC
was achieved in 66.7% of the TT + CTG and 47.4% of the TT + CGF (p < 0.05). The increase in KTW and GT was significantly
better in the TT + CTG group compared to the TT + CGF (p < 0.05).
Conclusions The study showed that TT + CGF did not improve the results as much as TT + CTG in the treatment of Miller Class I
and II GR. However, this finding is not sufficient to advocate the true clinical effects of CGF on GR treatment with TT.
Clinical relevance CGF could not serve as a direct alternative biomaterial to the gold standard CTG.
Trial registration ClinicalTrials.gov Identification Number: NCT04561947

Keywords Gingival recession . Growth factors . Plastic periodontal surgery . Connective tissue graft

Introduction and inability to always achieve the graft of the desired size [4,
5]. To overcome these disadvantages, attempts have been
Many techniques and biomaterials have been used for treat- made to search for materials alternative to CTG [1, 6]. One
ment of gingival recessions (GR) [1]. Connective tissue graft of these materials is platelet concentrates (PCs) [7–9].
(CTG) and coronally advanced flap (CAF) have been accept- Growth factors (GFs) released from platelets are important
ed as the most effective surgical techniques in regard to root for wound healing and increase cell angiogenesis, prolifera-
coverage predictability and long-term stability and have been tion, and extracellular matrix synthesis [10]. Therefore, the
stated as the gold standard [1–3]. In some cases, the disadvan- use of platelet-derived GFs for tissue regeneration in peri-
tages of CTG are inadequate palate tissue thickness, creating a odontal plastic surgery has been suggested [6, 7].
secondary surgical area that increases morbidity for a patient, Concentrated growth factor (CGF) is obtained by centrifuging
venous blood in a special centrifuge device at varying speeds
(2400 to 3000 rpm) [11]. In CGF isolation, the modified speed
* Birsen Korkmaz ratio is used rather than the constant speed used while obtaining
[email protected] platelet-rich fibrin (PRF). Thus, it is stated that a dense matrix is
formed in a way that allows increase of GF release [12].
1
Department of Periodontology, Faculty of Dentistry, Bulent Ecevit
CGF contains thrombocytes, leukocytes, and abundant
University, Zonguldak, Turkey GFs including transforming growth factor-beta 1 (TGF-β1),
2
Department of Periodontology, Faculty of Dentistry, Bezmialem
platelet-delivered growth factor (PDGF), vascular endothelial
Vakif University, Istanbul, Turkey growth factor (VEGF), insulin-like growth factors (IGF),
6348 Clin Oral Invest (2021) 25:6347–6356

fibroblast growth factor (FGF), and bone morphogenic protein To the best of our knowledge, this is the first study which
(BMP) in a complex three-dimensional fibrin network [11, 13, compares CGF and CTG in terms of root coverage efficiency
14]. This fibrin network is highly cohesive due to the presence using TT. The aim of this study was to evaluate the success of
of thrombin, factor XIII, and fibrinogen. Factor XIIIa, activat- CGF with TT and to compare it with the gold standard CTG in
ed by thrombin, causes the coagulation of fibrin. This protects the treatment of GR.
the clot from plasmin degradation and provides high tensile
strength and stability [11, 15].
Some studies have reported the biological and mechanical Materials and methods
advantages of CGF compared with PRF. CGF has a rigid tex-
ture thanks to its interwoven fiber structure [16, 17]. The fibrin Study design
matrix of CGF is larger and denser and contains more GF as a
result of different centrifuge speeds [18]. Lee et al. stated that This study was a single-center, parallel-group design, random-
CGF has stronger tensile strength and higher potential to induce ized controlled clinical study including 40 individuals who
proliferation of osteoblast and gingival fibroblast compared applied to the Department of Periodontology, Bulent Ecevit
with PRF [19]. Moreover, the GFs are homogeneously distrib- University, between October 2017 and July 2018. The study
uted in the plasma protein layer of CGF, and the release of the protocol in accordance with Declaration of Helsinki, as
GFs is for a longer duration compared with that for the usual revisited in 2000, was approved by Clinical Research Ethics
fibrin clot because of the fibrin matrix [20, 21]. The high tensile Committee of University with the protocol number 2017-82-
strength and viscosity of CGF protect GFs from proteolysis and 09/08 (ClinicalTrials.gov ID: NCT04561947).
prolong the release time of GFs [15]. GFs release due to con-
tinuous collision and rupture of platelets increases during cen- Sample size calculation
trifugation in the preparation of CGF [22]. Studies have shown
that CGF is slowly dissolved and released GFs for more than Data in two studies were used as guide to estimate sample size
13 days [21, 23]. Thus, CGF functions as a biomaterial that is a calculation [33, 34]. According to difference in root coverage
reservoir of integrated GFs [24]. of 1±0.9 mm (80% power which is equal β = 0.20 type II error
Many studies have shown the bioactivity, GFs content, and level with 5% type I error level which is equal α = 0.05
GFs release times of CGF [15, 16, 24, 25]. CGF stimulates the probability level), 14 participants in every group were needed.
proliferation, osteogenic maturation, and mineralization of In addition to these 14 participants, six more were recruited for
mesenchymal stem cells. Also, it has a good regenerative ca- each group to make up for any potential withdrawals.
pacity and versatility by increasing proliferation of the peri-
odontal ligament stem cells [26]. The high regeneration, vas- Investigator calibration
cularization, and angiogenesis capacity of CGF may be asso-
ciated with the presence of CD34 (+) cells [11, 12, 22]. The investigator calibration was provided to determine the
CGF is used in a wide variety of application areas, includ- repeatability of clinical measurements made by the researcher.
ing extraction sockets, sinus-lifting operations, alveolar ridge For this purpose, clinical measurements were made twice at an
augmentation, treatment of GR, and guided bone regenera- interval of 72 h in 20 defects of 5 patients. The repeatability of
tion, and achieved good results [8, 22, 27]. the measurements made by the researcher using the correla-
Scientific and technical innovations in the field of peri- tion coefficient was determined as 90% [7].
odontal plastic surgery and the increasing aesthetic expecta-
tions of patients have enabled the development of existing Patient population
treatment approaches. These developments have focused es-
pecially on wound healing and on increasing the blood supply The inclusion criteria were as follows: (1) age ≥ 18 years; (2)
of the treated area [28]. It is believed that the tunnel technique periodontally and systemically healthy; (3) presence of Miller
(TT), in which vertical releasing incisions are not performed, Class I or II GR defects in at least two teeth on the buccal
provides better nutrition to the area because of the blood sup- aspect of maxillary or mandibular incisors, canines, and pre-
ply provided to the flap and graft. Moreover, the aesthetic molars (≥ 2 mm in depth); (4) gingival thickness (GT) ≥
results are considered to develop due to avoiding the 0.8 mm at 2 mm apical from gingival margin; (5) presence
use of vertical incisions and no dissection of the papil- of identifiable cementoenamel junction (CEJ) (step ≤ 1 mm at
lae [29]. The TT is reported to provide some advantages the CEJ level and/or presence of a root irregularity/abrasion
such as reduced patient morbidity and faster and earlier with identifiable CEJ was accepted); (6) full-mouth plaque
healing [30–32]. The use of TT and its modifications score (FMPS) and full-mouth bleeding score (FMBS) ≤
for treatment of GR have been reported to provide high- 20%. The exclusion criteria were as follows: (1) smoking;
ly effective and aesthetic results [28, 29]. (2) contraindications for surgical periodontal treatment; (3)
Clin Oral Invest (2021) 25:6347–6356 6349

presence of recession defects associated with caries, restora- to advance the flap in the coronal direction and prevent the
tion, and deep abrasion; (4) use of systemic antibiotics for any collapse of the sutures on the interproximal areas.
reason in the last 3 months; (5) pregnant or lactating women. The patients were randomly assigned to one of the two
The study plan was explained to the patients by giving treatment groups by the flip of a coin by an independent third
detailed information about the treatments to be applied before person immediately before the surgery. After local anesthesia,
any procedure, and the informed consent forms were signed. the exposed root surfaces were mechanically treated with cu-
Four weeks prior to surgery, all patients were given detailed rettes (Gracey Curettes, Hu-Friedy, Chicago, IL, USA).
oral hygiene instructions to modify their oral hygiene habits. Tunneling knives (Stoma, Emmingen-Liptingen, Germany)
The full-mouth professional tooth cleaning was performed. were used to prepare a split-thickness flap and create a con-
The patients were re-evaluated; if they met the inclusion tinuous tunnel in the buccal soft tissues, following the
criteria, they were scheduled for the surgical periodontal treat- intrasulcular incision with a microblade (69 WS Swann-
ment. TT + CTG was applied to 20 patients in the control Morton, Sheffield, England). Split-thickness flap preparation
group (51 defects) and TT + CGF was applied to 20 patients was performed beyond the mucogingival junction with
in the test group (57 defects). supraperiosteal dissection by placing the tunneling knives to
the soft tissue. This process was repeated by entering through
Primary and secondary outcome variables the sulcus of each tooth. After the elevation of the flap, a
papilla elevator placed under the flap was entered through
Complete root coverage (CRC) was established as the primary the sulcus to mobilize the papilla, the periosteum at the base
outcome variable, while mean root coverage (MRC), GT, gin- of the papilla was cut, and the full-thickness flap was elevated.
gival recession width (RW), gingival recession depth (RD), Thus, the entire buccal soft tissue complex was mobilized
and keratinized tissue width (KTW) were the secondary out- coronally.
come variables.

Preparation of CTG and CGF membrane

Clinical measurements
After the tunnel was prepared, CTG was harvested using the
FMPS and FMBS were evaluated before the surgery [35, 36]. de-epithelialized graft technique [38]. The epithelial tissue on
PD: The distance between the sulcus base and the gingival the outer surface of the graft was removed with a 15 blade, and
margin in the midbuccal aspect of the teeth; CAL: distance a 1-mm-thick graft was obtained. After the CTG was harvest-
between the sulcus base and the CEJ in the midbuccal aspect ed, donor site was covered by a hemostatic sponge. The sur-
of the teeth; RD: distance between the gingival margin at the gical procedure in the test group was prepared as in the control
deepest point of recession and the CEJ; RW: horizontal dis- group. Intravenous blood samples were collected in two tubes
tance between the mesial and distal margin of the recession of 10 mL without anticoagulant (Vacuette tubes, Greiner Bio-
defect at the CEJ; KTW: distance between the gingival margin One, GmbH, Kremsmunster, Austria) and immediately cen-
and the mucogingival junction; GT: measured midbuccally trifuged in a CGF centrifuge machine (Medifuge, Silfradent,
from 2 mm apical to the gingival margin with a No. 20 end- S.Sofia, Italy) using a program with the following features:
odontic spreader with a rubber stopper and evaluated with a accelerated for 30 s; centrifuged at 2700 rpm × 2 min, 2400
precision caliper with 0.05 resolution. rpm × 4 min, 2700 rpm × 4 min, and 3000 rpm × 3 min; and
The CRC and MRC in the present study were calculated in decelerated for 36 s to stop.
the same way as Naik et al.’s study [37]. Acrylic stents were After centrifugation, four layers were formed in the tube:
used to standardize clinical measurements. Clinical measure- the serum layer at the top, the second buffy coat layer, the third
ments were made at baseline and at 6 months by a single blind CGF layer containing GF and unipotent stem cells, and the red
investigator (U.B.) using a periodontal probe (UNC-15, Hu- blood cell layer at the bottom [11]. The resulting CGF was
Friedy, Chicago, IL, USA), guided by previously prepared removed from the tube and separated from the red blood cell
acrylic stents. The values obtained were recorded the nearest layer using microsurgical scissors. CGF was made into a
0.5 mm. thickness of 1 mm membrane (Fig. 1) with a special pressing
kit. Both the CTG and CGF membranes were placed horizon-
Surgical technique tally at or 1 mm below the CEJ, and were stabilized with the
monofilament absorbable sutures (PGCL, Katsan 6/0 13 mm
All surgeries were performed by the same researcher (B.K.) 3/8, Izmir, Turkey). The buccal soft tissue complex was
using the TT as described by Zuhr et al. [31]. Before the coronally positioned and sutured with a double cross-suture
surgery, temporary suspension points were created with a flu- technique with monofilament nonabsorbable sutures
id composite at the contact point of the teeth to be treated so as (Polypropylene, Katsan 5/0 18 mm 3/8, Izmir, Turkey) [39].
6350 Clin Oral Invest (2021) 25:6347–6356

Results

The study was completed with 108 defects in 40 patients

(mean age 41.1 ± 9.3; min: 26; max: 63). Furthermore, 51
defects in the TT + CTG group were located at 16 incisors
(11 upper, 5 lower), 15 canines (11 upper, 4 lower), and 20
premolars (12 upper, 8 lower). Fifty-seven defects in the TT +
CGF group were located at 21 incisors (13 upper, 8 lower), 13
canines (9 upper, 4 lower), and 23 premolars (14 upper, 9
lower). Seventy of the defects were located in maxilla (TT +
CTG group: 34, TT + CGF group: 36), whereas 38 of the
defects were in mandible (TT + CTG group: 17, TT + CGF
group: 21). Wound healing was uneventful in both groups
after the treatment, and no complications were encoun-
tered in the recipient site. In 5 patients of the control
group, some postoperative complications, such as post-
operative bleeding (one patient) and pain (four patients),
were reported in the donor site. But these cases did not
require any additional intervention. All patients included
in the study completed the study by regularly participat-
ing in the control sessions (Fig. 2).
At baseline, there was no significant difference in the charac-
teristics of the defects and clinical parameters in the test and
control groups. All parameters except PI, GI, and PD were sta-
Fig. 1 CGF membrane
tistically different at 6 months compared with the baseline (p <
0.05). Patients achieved good plaque control at 6 months of
evaluation compared with the baseline: PI ≤ 20% and GI = 0
A nonsteroidal anti-inflammatory drug (ibuprofen 600 mg scores. The comparisons between the clinical view of the patients
twice a day) was prescribed to reduce postoperative pain and at baseline and 6 months are shown in Figs. 3, 4, 5, and 6.
edema. It was recommended to use 0.12% chlorhexidine glu- PD: No statistically significant difference was found in
conate (CHX) mouthwash three times a day. The sutures were both groups during the study period (Table 1).
removed 14 days after the surgery, and plaque control was CAL: In both groups, a significant decrease was achieved
provided with CHX for another 2 weeks. Furthermore, the at 6 months compared with the baseline. However, there was
patients were proposed to gently brush the surgical area using no statistically significant difference in the comparison be-
the roll technique with an ultra-soft toothbrush. They were tween groups (Table 1).
regularly invited to control sessions. RD and RW: A statistically significant decrease was ob-
served in both test and control groups at 6 months compared
with the baseline (p < 0.05). No difference was observed be-
Statistical analysis tween the groups at 6 months compared with the baseline
(Table 1).
Statistical evaluation was performed using the SPSS 19.0 KTW: The increase of KTW between baseline and 6
program (SPSS Inc., IL, USA). The data were analyzed months was statistically significant in both groups (p <
in terms of compliance with normal distribution using 0.05). There was a significant higher value in the control
the Shapiro-Wilk test. The Mann-Whitney U test was group compared with the test group (Table 1).
used to analyze the statistically significant difference be- GT: In both groups, there was a significant increase in GT
tween the medians of the independent groups in the data at 6 months compared with the baseline values (p < 0.05). The
that did not fit the normal distribution in terms of nu- increase in the control group was significantly higher than in
merical variables. Wilcoxon’s signed-rank test was used the test group (Table 1).
to analyze the difference before and after treatment be- MRC: MRC was 89.52 ± 16.36% and 76.60 ±
tween groups. Comparison between groups for CRC was 24.10%, respectively, in the control and test groups. A
made using the chi-square test. Descriptive statistics were statistically significant difference was found in favor of
expressed as mean ± standard deviation. Statistical sig- the control group in the intergroup comparison at 6
nificance was established for p < 0.05. months (p = 0.004) (Table 2).
Clin Oral Invest (2021) 25:6347–6356 6351

Fig. 2 Consort flow diagram of

the study

CRC: CRC was achieved in 34 (66.7%) of 51 defects in the addition to GR treatment might have positive effects, shorten-
control group and 27 (47.4%) of 57 defects in the test group. ing the surgical time in patients requiring large amounts of
The difference between the groups was statistically significant CTG, and could be a potential alternative [44]. Many studies
in favor of the control group (p = 0.043) (Table 2). comparing CAF with CTG and PRF suggested that PRF
showed good results for all parameters and could be a success-
ful alternative to the gold standard CTG [45].
Discussion A recent meta-analysis reported that PRF used in addition
to CAF surgery was associated with higher percentage of root
GFs are bioactive proteins secreted by platelets, which control coverage, but did not create a significant change in terms of
wound healing [40]. Clinical outcomes can be improved with KTW. Studies comparing CTG and PRF achieved better re-
the use of GFs in the treatment of GR [41]. Limited data exist sults in the CTG group in terms of KTW and percentage of
on the use of CGF, the new-generation PC, in the treatment of root coverage, and CTG was a better option in patients with
GR compared with the commonly used PRF [8, 42]. This KTW insufficiency and deficiency [46].
randomized controlled clinical trial was designed to evaluate Based on the available information and results, it was still
the effectiveness of TT + CGF in the treatment of multiple not possible to clearly conclude about the use of PRF in the
Miller Class I/II GR and whether CGF was an alternative treatment of GR. The variety of results could be explained
biomaterial to CTG. The results showed that both techniques considering different PRF properties resulting from different
were effective in the treatment of GR, but better results were PRF preparation protocols, process of collecting blood, cell
obtained in the CTG group in terms of KTW, GT, and root counts, and concentrations of GFs [47].
coverage percentages at 6 months. Unlike other PCs, CGF is obtained with a centrifuge pro-
The results of studies comparing CTG and PC were con- tocol at varying speeds in a special centrifuge device (accel-
tradictory. A systematic review evaluating the effects of PC on erated for 30 s; centrifuged at 2700 rpm × 2 min, 2400 rpm × 4
surgical periodontal treatment results reported that PC did not min, 2700 rpm × 4 min, and 3000 rpm × 3 min; and deceler-
provide a significant benefit in the treatment of GR [43]. ated for 36 s to stop) [11]. The centrifuge devices and proto-
Another systematic review showed that the use of PC in cols used for PRF production vary considerably. The changes

Fig. 3 Control group. a

Preoperative view. b Immediate
postoperative view. c 6 months
postoperative view
6352 Clin Oral Invest (2021) 25:6347–6356

Fig. 4 Test group. a Preoperative

view. b Immediate postoperative
view. c 6 months postoperative
view

to be made in centrifuge speed and time might affect the achieved with both techniques [54]. In the 6-month results of
PRF’s cell content and number, growth factor, and fibrin ma- their study comparing the modified TT + CTG and the mod-
trix directly; change its biological activities; and cause differ- ified TT + titanium-prepared PRF (T-PRF), Uzun et al. [9]
ences in clinical results [48, 49]. In this respect, it has been showed the MRC was 91.06% for T-PRF and 92.04% for
reported that CGF may be more stable and suitable for acquir- CTG, with no difference between groups. In the 12th month
ing predictable results since CGF is obtained with more con- results of their study, the MRC was reported to be 93.29% for
sistent centrifuge protocols [50]. the T-PRF and 93.22% for the CTG group; the results obtain-
CTG is still the most suitable graft material in the treatment ed at the end of the study period were stable. The MRC and
of gingival recession. However, it causes increased patient CRC in the present study were lower than those in their study.
morbidity [4, 5]. PRF has positive effects on wound healing The details of TT in their study indicated that the researchers
in various soft tissue defects and reduces postoperative pain used a 3-mm vertical incision in the alveolar mucosa close to
and discomfort regardless of the type of PRF used [51, 52]. In base of the vestibule. No vertical incision was used in the TT
addition, it is easy to use and inexpensive, and requires less applied in the present study. It was believed that this situation
time. PRF should be considered a living tissue for natural might directly affect the CRC and MRC. The lower MRC and
guided tissue regeneration rather than just a growth factor– CRC in the present study may be related to the different sur-
rich surgical adjuvant [52]. With these advantages, the use gical approaches used.
of PRF and/or CGF in treatment of gingival recession may In a study evaluating the effect of CTG thickness on surgi-
be effective. cal outcomes, no statistically significant differences were
In the present study, MRC and CRC were found to be found between the 1 mm and 2 mm thick groups, but a ten-
89.52% and 66.7%, respectively, in the CTG group and dency for improved outcomes in terms of root coverage, GT,
76.6% and 47.4%, respectively, in the CGF group. The and KTW for 2 mm thick CTG is noted in the third month
MRC and CRC values in the TT + CTG group in this study [55]. In the treatment of gingival recessions, PRF should be
were compatible with the recent systematic review [53]. In a applied in at least two layers, if possible in three layers, so that
study by Bozkurt Dogan et al. [8], MRC and CRC were re- the desired volume is reached [56]. Studies on this subject are
ported as 86.67% and 45.8%, respectively, in the CAF + CGF limited. Culhaoğlu et al. [57] obtained much better results
group, with no significant difference between the groups. with 4 PRF layers than with 2 PRF layers in terms of root
They stated that CGF did not provide an additional benefit coverage in the treatment of gingival recessions and found
in terms of root coverage. Akcan and Unsal [42] in their study that the effects of 4 PRF layers and CTG were similar. In
comparing CAF + CTG and CAF + CGF stated the MRC is the present study results, this situation might affect obtaining
52.45% for the CGF group and 72.45% for the CTG group. lower MRC, CRC, and GT values with CGF compared with
They reported that CTG provided superior results in terms of CTG. Increasing the layer of CGF can improve these results;
GT, KTW, and root coverage, but CGF was more preferable however, further studies testing this hypothesis are needed.
in reducing postoperative pain. According to these results, In the current study, the mean KTW increased from 2.10 ±
although CGF did not improve the outcomes of root coverage, 0.49 to 4.80 ± 0.57 mm in the TT + CTG group and from 2.26
it is not possible to reach a clear conclusion due to insufficient ± 0.40 to 2.81 ± 0.56 mm in the TT + CGF group; this increase
clinical evidence. In a case report, multiple Miller Class II GR was statistically significantly higher in the CTG group. In the
were treated with TT + PRF and TT + CTG and followed up present study, as in previous studies, KTW increased in the
for 45 days, revealing that successful root coverage (90%) was CGF group [8, 42]. Akcan and Unsal [42] demonstrated a

Fig. 5 Control group. a Preoperative view. b 6 months postoperative view Fig. 6 Test group. a Preoperative view. b 6 months postoperative view
Clin Oral Invest (2021) 25:6347–6356 6353

Table 1 Descriptive statistics of the clinical parameters measured at the increase in the groups in the present study were consistent
baseline and 6 months after the surgery
with previous studies [57–59]. Many GFs released from plate-
Control group (n = 51) Test group (n = 57) p value lets in the natural fibrin matrix of PRF increased KTW by
Mean ± SD Mean ± SD positively affecting the proliferation of gingival/periodontal
fibroblasts [7, 60]. Based on these studies, it is presumed that
PD
CGF, which contains more GFs [11, 22], may have a similar
Baseline 1.42 ± 0.41 1.37 ± 0.26 0.834
effect. The increase in KTW in the CTG group could be ex-
6 months 1.37 ± 0.40 1.26 ± 0.35 0.314
plained by the ability of CTG to induce the keratinization of
p value 0.284 0.103
the epithelium [61].
CAL
In the present study, an increase of 0.94 ± 0.05 mm in the
Baseline 3.96 ± 0.67 3.83 ± 0.56 0.482 CTG group and 0.26 ± 0.09 mm in the CGF group was ob-
6 months 1.64 ± 0.48 1.88 ± 0.59 0.225 served in the GT values, and this increase was found to be
p value 0.000* 0.000* significantly higher in the CTG group. Studies have reported
RD that the use of CGF increases GT significantly [8, 42]. Most
Baseline 2.53±0.66 2.45±0.45 0.805 studies showed that PRF increased GT values, but better re-
6 months 0.26±0.34 0.62±0.57 0.053 sults were obtained in the CTG group [9, 57]. The results of
p value 0.000* 0.000* the present study were compatible with previous studies. The
RW increase in GT with PRF might be due to the proliferative
Baseline 3.56±0.51 3.37±0.37 0.222 effect of GFs on gingival/periodontal fibroblasts or the space
6 months 1.14±0.99 1.13±1.43 0.585 provided by the PRF membrane with histoconduction [7, 9].
p value 0.000* 0.000* The significant increase in GT in the CTG group compared
KTW with the CGF group may be explained by that CGF does not
Baseline 2.10±0.49 2.26±0.40 0.722 serve as good scaffold supporting the migration of cells from
6 months 4.80±0.57 2.81±0.56 0.000* adjacent tissues.
p value 0.000* 0.000* A meta-analysis reported no difference between CTG and
GT PRF in terms of PD and CAL [46]. In this study, the decrease
Baseline 1.16±0.05 1.19±0.05 0.101 in PD values and the significant increase in CAL obtained in
6 months 2.10±0.10 1.45±0.14 0.000* both groups were compatible with those in other studies [7, 8].
p value 0.000* 0.000* More reliable results could be obtained with the split-
mouth design to minimize the individual differences depend-
CAL, clinical attachment level; GT, gingival thickness; KTW, keratinized
ing on patient. In such a manner, the inter-patient influence on
tissue width; PD, probing depth; RD, recession depth; RW, recession
width post-surgical wound healing could be reduced for both surgi-
Data are expressed as the mean ± standard deviation cal procedures. This study had some limitations. First, this
Wilcoxon signed-rank test study was designed as parallel group, but initial RD, RW,
*
p < 0.05 GT, and KTW values were similar in both groups, minimizing
the negative effect of this factor. In addition, the results of this
study were limited to only short 6 months follow-up period,
statistically significant increase in KTW in the CTG group and patient-related outcomes (such as pain, patient satisfac-
compared with CGF. Many studies reported that the use of tion, and aesthetics) were not evaluated. Another limitation of
CTG increased the KTW more statistically significantly com- this study was that histological analysis was not performed to
pared with PRF, and the use of CTG to increase KTW was a evaluate the regenerative capacity of CGF. Therefore, no com-
more suitable option [46, 57–59]. Thus, the results on KTW ments could be made on the type of tissue formed.

Table 2 Mean and complete root

coverage in the operated patients Control group (n = 51) Test group (n = 57) p value
6 months after the surgery
Mean root coverage 82.52±16.36 76.60±24.10 0.0041*
Complete root coverage 34/51 (66.7%) 27/57 (47.4%) 0.0432*

Data are expressed as the mean ± standard deviation

1
Wilcoxon signed-rank test
2
Chi-square test
*
p < 0.05
6354 Clin Oral Invest (2021) 25:6347–6356

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patient and clinician want to reduce morbidity, and are willing evaluation of a modified coronally advanced flap alone or in com-
to accept less than optimal results. However, this finding is not bination with a platelet-rich fibrin membrane for the treatment of
sufficient to advocate the true clinical effects of CGF on gin- adjacent multiple gingival recessions: a 6-month study. J
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investigate and compare the effectiveness of CGF in terms of (2015) Concentrated growth factor in the treatment of adjacent
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Acknowledgements The authors do not have any financial interest in the
ity of titanium-prepared platelet-rich fibrin for the management of
companies whose materials are included in this study.
multiple gingival recessions. Clin Oral Investig 22(3):1345–1354.
https://doi.org/10.1007/s00784-017-2211-2
Author contribution All authors have made substantial contributions to 10. Anitua E, Andia I, Ardanza B, Nurden P, Nurden A (2004)
conception and design of the study. BK contributed to the design of the Autologous platelets as a source of proteins for healing and tissue
study, treated the patients, analyzed the data, and wrote the manuscript regeneration. Thromb Haemost 91:14–15. https://doi.org/10.1160/
with input from the other author. UB was involved in data collection and TH03-07-0440
interpretation, and revised it critically. All authors have given final ap- 11. Rodella LF, Favero G, Boninsegna R, Buffoli B, Labanca M, Scarì
proval of the version to be published. G, Sacco L, Batani T, Rezzani R (2011) Growth factors, CD34
positive cells, and fibrin network analysis in concentrated growth
Funding This study was supported by the Scientific Research Fund of factors fraction. Microsc Res Tech 74(8):772–777. https://doi.org/
Bulent Ecevit University in Zonguldak/TURKEY (Project Number: 10.1002/jemt.20968
2017-62550515-01). 12. Sohn DS, Heo JU, Kwak DH, Kim DE, Kim JM, Moon JW, Lee
JH, Park IS (2011) Bone regeneration in the maxillary sinus using
Declarations an autologous fibrin-rich block with concentrated growth factors
alone. Implant Dent 20(5):389–395. https://doi.org/10.1097/ID.
0b013e31822f7a70
Ethics approval All the procedures performed in the study involving 13. Qiao J, Na A, Ouyang X (2017) Quantification of growth factors in
human participants were in accordance with the ethical standards of the
different platelet concentrates. Platelets 28(8):774–778. https://doi.
institutional and/or national research committee and with the 1964
org/10.1080/09537104.2016.1267338
Helsinki Declaration and its later amendments or comparable ethical
14. Bonazza V, Hajistilly C, Patel D, Patel J, Woo R, Cocchi MA,
standards.
Buffoli B, Lancini D, Gheno E, Rezzani R, Jahanzeb S, Hunnisett
A, Almasri M, Lucchina AG, Brucoli M, Mortellaro C, Rodella LF
Consent to participate Informed consent was obtained from all individ- (2018) Growth factors release from concentrated growth factors:
ual participants included in the study. effect of beta-Tricalcium phosphate addition. J Craniofac Surg
29(8):2291–2295. https://doi.org/10.1097/SCS.
Conflıct of interest The authors declare no competing interests. 0000000000004607
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