J Clin Exp Dent. 2021;13(2):e190-200.

PRF and palatal wound healing

Journal section: Periodontology doi:10.4317/jced.57451

Publication Types: Review https://doi.org/10.4317/jced.57451

Platelet-rich fibrin for wound healing of palatal donor sites of free

gingival grafts: Systematic review and meta-analysis

David-Jonathan-Rodrigues Gusman 1,2, Henrique-Rinaldi Matheus 1, Breno-Edson-Sendão Alves 1,3, Aman-

da-Munarolo-Piacenza de Oliveira 2, Amanda-Cristine-dos Santos Britto 2, Vivian-Cristina-Noronha Novaes 4,
Maria-José-Hitomi Nagata 1, Victor-Eduardo-de Souza Batista 2, Juliano-Milanezi de Almeida 1

1
Department of Diagnostic and Surgery – Periodontics Division. São Paulo State University (UNESP), School of Dentistry, Araçatuba
2
Department of periodontics, University of Western Sao Paulo (UNOESTE), Presidente Prudente, Sao Paulo, Brazil
3
Department of periodontics, Maringa University Center (UNINGA), Maringa, Parana, Brazil
4
Department of periodontics, University Center of Santa Fe do Sul (UNIFUNEC), Santa Fe do Sul, Sao Paulo, Brazil

Correspondence:
Universidade do Oeste Paulista (UNOESTE)
Rua Jose Bongiovani, 700 - Cidade Universitária
Presidente Prudente, 19050-920, Sao Paulo, Brazil
[email protected]

Received: 09/06/2020
Accepted: 23/09/2020 Gusman DJR, Matheus HR, Alves BES, de Oliveira AMP, Britto ACS,
Novaes VCN, Nagata MJH, Batista VES, de Almeida JM. Platelet-rich
fibrin for wound healing of palatal donor sites of free gingival grafts: Sys-
tematic review and meta-analysis. J Clin Exp Dent. 2021;13(2):e190-200.

Article Number: 57451 http://www.medicinaoral.com/odo/indice.htm

© Medicina Oral S. L. C.I.F. B 96689336 - eISSN: 1989-5488
eMail: [email protected]
Indexed in:
Pubmed
Pubmed Central® (PMC)
Scopus
DOI® System

Abstract
Background: Platelet-rich fibrin (PRF) has been referred to as a second-generation platelet concentrate, associated
with improvements on the healing of palatal wounds followed by FGG harvesting. The aim of this systematic re-
view and meta-analysis was to assess the complete wound epithelialization and postoperative pain when PRF was
used in palatal wounds following free gingival graft (FGG) harvesting.
Material and Methods: PubMed (Medline), EMBASE and Scopus were searched by two independent individuals
up to and including March 2020 in order to identify controlled and randomized controlled clinical trials on the use
of PRF at palatal donor sites of FGG. The outcomes assessed were epithelialization and postoperative pain. The
risk of bias of the included studies was evaluated using Cochrane Collaboration’s domain-based two-part tool.
Random effects meta-analyses were conducted with 95% confidence intervals.
Results: The search strategy identified 555 potentially eligible articles, of which 6 randomized controlled clinical
trials were included. In the qualitative analysis, most studies (83.3%) reported lower postoperative pain in treatment
groups, while all studies accessing epithelialization demonstrated earlier complete wound closure in groups treated
with PRF. The discomfort and complete re-epithelialization were more favorable in groups PRF when compared to
control groups (P<0.00001).
Conclusions: Within the limits of the present study, it can be concluded that the use of PRF for wound healing of
palatal donor sites of FGG may decrease postoperative pain and induce earlier complete wound epithelialization.

Key words: Wound healing, oral surgery procedures, pain, postoperative.

e190
J Clin Exp Dent. 2021;13(2):e190-200. PRF and palatal wound healing

Introduction rred Reporting Items for Systematic Reviews and Me-

The percentage of individuals affected by gingival re- ta-Analyses (PRISMA) statement guidelines (12).
cessions varies depending on populations, averaging -Information sources, search, study selection
from 30% to 100% (1). In addition, the prevalence and Two independent reviewers (D.J.R.G., V.C.N.N.) con-
severity of this condition seems to increase with age (1). ducted an electronic search on the PubMed/Medline,
Gingival recessions predispose to reduction in the width EMBASE, and Scopus databases for articles published
of keratinized gingiva, aesthetic deficiency and dentin in English language, until 02sd March 2020. The key
hypersensitivity, leading to pain during patients’ self-ca- words used were: “palatal wound healing and free gin-
re (1). Some therapies are proposed in order to reduce gival graft; donor site wound healing and free gingival
recessions’ negative impact. Free gingival grafts (FGG) graft; donor site wound healing and connective tissue
and connective tissue grafts (CTG) have been perfor- graft; palatal wound healing and connective tissue graft;
med to increase the width of keratinized gingiva and for palatal wound healing and platelet-rich fibrin”. A further
root coverage, aiming reduction or elimination of dentin manual search was conducted on the reference lists of
hypersensitivity and to recover aesthetics (1). relevant journals in the field (Journal of Clinical Perio-
Different autologous sites are eligible to be donors of dontology, Journal of Periodontology and Journal of
FGG and CTG, such as edentulous areas, maxillary tube- Periodontal Research). The authors also performed a
rosity and palatal mucosa (1,2). Among them, the palate search of non-peer-reviewed literature at http://www.
is the most usually chosen donor site (3). The surgical opengrey.eu/. All potential abstracts and complete texts
intervention for removal of FGG is relatively easy to be were revised for selection of those that met the crite-
performed and enables obtention of substantial amount ria detailed below. Disagreements between researchers
of tissue (1). However, this procedure is almost always were settled by consensus. Cohen’s kappa coefficient
related to, at least, one of the following complications: was used to evaluate the agreement between researchers.
acute pain, hemorrhage, and bone exposure, which lead In accordance with the PICO framework (12), it was
to morbidity and discomfort for the patient during the used the focus question: “Can platelet-rich fibrin to im-
healing process of the donor site (4). It generally takes prove epithelialization and to reduce postoperative pain
2-4 weeks for FGG palatal wounds to heal by secondary at the donor site of FGG?”
intention (5). • Population: adult patients that underwent surgical re-
Aiming to avoid or to overcome these issues, studies moval of FGG from their palates;
have reported some therapeutic alternatives for enhance- • Intervention: adaptation of platelet-rich fibrin at the
ment in the repair process and/or to reduce postoperative donor site of FGG;
pain of palatal donor sites of FGG, such as low-level-la- • Comparison: with their respective control groups (ste-
ser-therapy (LLLT) (6), ozone therapy (6), platelet rich rile wet gauze pressure, natural wound closure, use of
plasma (7), and others. gelatin sponge, butyl-cyanoacrylate, or wound coverage
The platelet rich fibrin (PRF) is referred to as the second with dressing materials)
generation of platelet concentrates, widely used in mo- • Outcomes: wound epithelialization (percentage of
dern medicine (8). In dentistry, it has been used to im- complete wound epithelialization [through H202 bub-
prove the repair process in post-extraction sockets, sinus bling], or analysis of contour changes rated by scores)
lifts, periodontal bone defects, and periodontal plastic and postoperative pain (visual analog scale [VAS]).
surgeries (9). The use of PRF in the palate following the -Eligibility criteria
removal of FGG was described by randomized contro- Controlled clinical trials and randomized controlled cli-
lled clinical trials (10, 11) aiming to reduce the postope- nical trials published in the English language, evaluating
rative pain and/or to improve healing. However, to the wound epithelialization and/or postoperative pain at the
best of our knowledge, no systematic review and me- donor site of FGG in healthy patients.
ta-analysis was performed on this topic. Articles that failed to meet the inclusion criteria: studies
Therefore, in order to confirm the hypothesis that PRF that did not evaluate wound epithelialization or postope-
could improve both parameters (i.e. healing and pain), rative pain; grafts collected by a different method than
the aim of this systematic review and meta-analysis the conventional technique described by Sullivan and
was to assess the complete wound epithelialization Atkins (1968) (2) (rectangular graft removal of palatal
and postoperative pain when PRF was used in palatal donor site [epithelium and connective tissue]).
wounds following FGG harvesting. -Data items and data collection process
One reviewer collected information from the selected
Material and Methods articles, including author, year of publication, country,
-Procedure type of study, groups evaluated, analyses and evalua-
This review is registered in the PROSPERO database tion period, preparation of PRF, prescribed medications,
(CRD42019129790), in compliance with the Prefe- the main outcome, and authors’ conclusion. A second

e191
J Clin Exp Dent. 2021;13(2):e190-200. PRF and palatal wound healing

reviewer checked all information collected by the first metry can show a true association between trial size and
reviewer. effect size (14). Heterogeneity was evaluated by the Q
-Risk of bias in individual studies method (x2) and the I2 value. An I2 of <60% was the
The risk of bias of the randomized controlled trials cut-off for homogeneity of the data, justifying pooling.
(RCTs) included was assessed using the Cochrane Co-
llaboration Tool for Assessing Risk of Bias in Randomi- Results
zed Trials (13). -Literature research
-Summary measures, risk of bias among the studies, The electronic search on the databases identified 555
synthesis of results articles (Figure 1 shows details of the research process
Meta-analysis was based on the inverse variance (IV) and studies’ selection). After elimination of duplicates,
and Mantel-Haenzel (M-H) methods. The discomfort a total of 444 articles were screened by title and abs-
was continuous outcome and assessed by mean diffe- tract. The articles not fulfilling the PICO framework
rence (MD) values. The complete re-epithelialization of were considered ineligible. At the end of this procedure,
the palatal wound was dichotomous outcome assessed 437 articles were excluded. Thus, seven full-texts were
by odds ratio (OR). A random-effects model was used to analyzed, and one article was excluded (15) due to the
assess the significance of the treatment effects (14) with different technique than Sullivan and Atkins (1968) (2)
corresponding 95% confidence intervals (CI). A com- for removal of the graft (single-incision), assigned in
puter software (Reviewer Manager 5; Cochrane Group) the exclusion criteria. Finally, six articles were selec-
was used to perform the meta-analysis and to produce ted for systematic review, (4,10,11,16,17,18) two arti-
the funnel plots. cles articles (4,16) for meta-analysis of postoperative
An asymmetric funnel plot can suggest publication bias pain (VAS), and two articles (10,16) for meta-analysis
or other biases related to sample size, although the asym- of complete wound epithelialization (H2O2 bubbling).

Fig. 1: Flow chart of manuscripts screened through the review process.

e192
J Clin Exp Dent. 2021;13(2):e190-200. PRF and palatal wound healing

Cohen’s kappa coefficient indicated 100% of agreement the amount of analgesics’ intake by the patients between
between reviewers. control and test groups. Ozcan et al. (10) prescribed no
-Assessment of risk of bias and quality assessment in analgesics, and İşler et al. (4) presented no data due to
included studies the lack of standardization.
A summary of the methodological quality assessment of Among the studies assessing the VAS, Femminella et al.
the studies included is described in figure 2. (16), Ozcan et al. (10), Bahamman, (11), İşler et al. (4),

Fig. 2: Risk of bias summary.

-Characteristics of the included studies related to patients and Sharma et al. (17) observed reduction of the posto-
A total of 247 patients were allocated to the control perative pain in different periods of analysis. Only Us-
groups and groups that had the palatal wound treated taoglu et al. (18) observed no difference in postoperative
with PRF. Among these patients, 140 were from control pain by using T-PRF.
groups, consisting of spontaneously secondary healing All studies evaluating the epithelialization of the palatal
(4), sterile wet gauze pressure (18), gelatin sponge (17), wound showed that PRF promoted complete healing in
butyl-cyanoacrylate (10), and bandage with non-euge- shorter time periods when compared with its respective
nol periodontal pack (coe-pak TM) (11) and collagen control groups, independent on the method of analysis
dressing (CollaCote®) (17). In test groups, 107 patients (peroxide test - H2O2-bubbling [10, 16, 18] or image
were treated with PRF bandage (4,16,17), platelet con- based scores [by five senior residents in blind periodon-
centrate obtained by centrifugation in titanium tubes tics]) (11). The results are described in table 1, 1 cont., 1
(T-PRF) and used as bandage (18), PRF + butyl-cyanoa- cont.-1, 1 cont.-2.
crylate (10), and PRF bandage + non-eugenol periodon- -Results of the meta-analysis
tal pack (coe-pak TM) (11). Two studies used the VAS criteria (4,16) to report the data
The mean age of the patients when considering both comparing the interventions. The quantitative analysis
control and test groups was 34.79 ± 7.87. This data was indicated difference between the PRF group and con-
obtained from 4 studies, since Ustaoglu et al. (18) and trol groups (P<0.00001) (Fig. 3). Two studies reported
Sharma et al. 2019 (17) did not mention the mean age of the data of complete re-epithelialization of the palatal
their patients. All studies included are randomized con- wound after 14 days (10, 16). The quantitative analysis
trolled clinical trials. indicated difference between the PRF group and control
Different medications were prescribed in the experi- groups (P<0.00001) (Fig. 4). The funnel plots showed
ments. Femminella et al. 2016 (16) and Bahamman (11) evident symmetry among the differences of means in the
reported lower use of analgesic in test groups. On the studies evaluated. The funnel plot showed symmetry in
other hand, Ustaoglu et al. (18) did not find difference in both outcomes (Figs. 3,4).

e193
 Table 1: Characteristics of studies included.

Author/ Country and Groups Analyses and Preparation of Prescribed medications Main outcome Author’s conclusion
Year type of study evaluation periods PRF
Femminella et al. Italy Control group Post-operative pain Chouckroum et al. Augmentin® (875mg amoxicillin + VAS The PRF-enriched
2016 (16) Gelatin sponge VAS 2000 125mg clavulanic acid) Control group palatal bandage signifi-
- 2x per day for 6 days 1st week: 4.6 ± 0.2 cantly accelerates pala-
Randomized N= 20 Weeks 1, 2, 3 e 4 2nd week: 2: 3.75 ± 0.22 tal wound healing and
J Clin Exp Dent. 2021;13(2):e190-200.

Clinical Trial Ketoprofen 80mg 3rd week: 2.6 ± 0.18 reduces the patient’s
Test group - if needed 4th week: 0.9 ± 0.17 morbidity.
PRF Complete re- Test group
epithelialization of 0.12% Chlorhexidine digluconate 1st week: 2.4 ± 0.2
N= 20 the palatal wound solution 2nd week: 1.75 ± 0.22
(H2O2-bubbling) - for 3 weeks 3rd week: 1.1 ± 0.18
Mean age of both Weeks 1, 2, 3 e 4 4th week: 0.15 ± 0.17
groups: 32.4 ± 5.0 Relevant information Complete re-epithelializa-
Lower use of analgesics in test tion of the palatal wound
group (number of patients)
(H2O2-bubbling)
Control group
1st week: 0
2nd week: 2
3rd week: 18

e194
4th week: 20
Test group
1st week: 0
2nd week: 7
3rd week: 13
4th week: 20
Ustaoglu et al. Turkey Control group Post-operative pain Tunali et al. 2013 500mg paracetamol VAS T-PRF can be used to
2016 (18) sterile wet gauze VAS - if needed did not differ between the accelerate wound heal-
pressure 1 to 7 post-operative two groups during the first ing at FGG donor sites
Randomized days 0.2% Chlorhexidine oral rinse week (not cited the results) by simulating a primary
controlled N= 20 - 2x per day for 2 weeks Complete wound epitheli- wound healing pattern
clinical trial Complete wound alization (H2O2-bubbling) but not results in lower
Mean age: not epithelialization Relevant information Control group post-operative pain
cited (H2O2-bubbling) The number of analgesics did not 3rd day: 0%
3, 7, 14 and 21 post- differ between the two groups 7th day: 0%
Test group operative days 14th day: 16.7%
T-PRF 21th day: 100%
Test group
N= 20 3rd day: 0%
7th day: 0%
Mean age: not 14th day: 68.7%
cited 21th day: 100%
PRF and palatal wound healing
 Table 1 cont.: Characteristics of studies included.

Ozcan et al. 2017 Turkey Control group 1 Post-operative pain Dohan et al. 2006 Analgesic medication was not pre- VAS PRF at the palatal
(10) sterile VAS scribed Control group 1 donor site after FGG
wet gauze com- 1st day: 6.10 harvesting
Randomized pression 1, 2, 3, 4, 5, 6, 7, 2nd day: 5.22 may provide significant
clinical trial 14, 21 and 28 post- 3rd day: 3.22 benefits in terms of
N = 41 operative days 4th day: 2.41 wound healing param-
J Clin Exp Dent. 2021;13(2):e190-200.

5th day: 1.58 eters

Mean age 6th day: 1.29 with post-operative bet-
37.61 ± 6.64 Complete wound 7th day: 1.02 ter pain perception
epithelialization Control group 2
Control group 2 (H2O2-bubbling) 1st day: 4.85
butyl-cyanoacry- Weeks 1, 2, 3 and 4 2nd day: 3.90
late alone 3rd day: 1.90
4th day: 1.21
N = 42 5th day: 0.88
Mean age 6th day: 0.12
37.11 7th day: 0
±4 Test group
1st day: 2.00
Test group 2nd day: 1.29
PRF + butyl- 3rd day: 0.26
cyanoacrylate 4th day: 0.12

e195
5th day: 0.02
N = 42 6th day: 0.00
7th day: 0.00
Mean age Complete wound epithe-
34.55 ± 7.64 lialization (number of
patients)
(H2O2-bubbling)
Control group 1
1st week: 0
2nd week: 5
3rd week: 36
4th week: 41
Control group 2
1st week: 0
2nd week: 11
3rd week: 31
4th week: 42
Test group
1st week: 0
2nd week: 36
3rd week: 6
4th week: 42
PRF and palatal wound healing
 Table 1 cont.-1: Characteristics of studies included.

Bahamman,2018 Kingdom of Control group Post-operative pain Dohan et al. 2006 1000 mg Acetaminophen VAS PRF palatal bandages
J Clin Exp Dent. 2021;13(2):e190-200.

(11) Saudi Arabia non-eugenol VAS - if needed Control group: significantly reduced
periodontal pack 1st day: 5.46 pain and discomfort in
(coe-pak TM) was 1 to 4 and 7 post- 0.12% Chlorhexidine gluconate 2nd day: 3.38 the postoperative pe-
Randomized applied operative days mouth rinse 3rd day: 3.94 riod and favored heal-
controlled as a protective - for 2 weeks 4th day: 0.86 ing process after FGG
clinical trial bandage Palatal wound Test group removal.
healing (analysis of Relevant information 1st day: 2.10
N = 12 contour changes) Lower use of analgesics in test 2nd day: 1.41
group 3rd day: 0.53
Mean age: 28.5 Five senior residents 4th day: 0.00
± 3.7 in blind periodontics Analysis of contour
(graduate) and a changes
Test group professional perio- Control group
Bandage of PRF dontist judged the 1st week: 3
+ non-eugenol clinical photographs 2nd week: 3

e196
periodontal pack and rated the follow- 3rd week: 2.29
(coe-pak TM) was ing scores: 4th week: 1.71
applied 8th week: 1.71
as a protective 1. exactly similar Test group
bandage cirúrgico to the pre-operative 1st week: 3
(coe-pak TM) photograph 2nd week: 3
2. some tissue ir- 3rd week: 2.14
N = 12 regularities can be 4th week: 1.43
detected 8th week: 1.20
Mean age: 27.8 3. severe depression
± 4.3 or extreme elevation
of the palatine
tissues detected

1, 2, 3, 4 and 8 weeks
after surgery
PRF and palatal wound healing
 Table 1 cont.-2: Characteristics of studies included.

İşler et al. 2019 Turkey Control group Post-operative pain Dohan et al. 2006 100mg flurbiprofen VAS It was observed that
(4) Spontaneous sec- - 3x per day for 1 week if needed Control group PRF applications may
Randomized ondary healing VAS 1st day: 2.2±3.4 have a favorable impact
controlled 0.12 Chlorhexidine mouth rinse 2nd day: 2.1±3.0 on the patient comfort
clinical trial N=10 1 to 7 post-operative - 2x per day for 3 weeks 3rd day: 0.3±0.5 with respect to the
days 4th day: 2.4±2.8 postoperative pain
Mean age: Relevant information 5th day: 3.9±3.1
J Clin Exp Dent. 2021;13(2):e190-200.

40.0±15.7 the number of analgesics could not 6th day: 2.4±3.2

be standardized (data not shown) 7th day: 1.9±2.0
Test group Test group
PRF 1st day: 0.7±1.5
2nd day: 0.3±0.5
N=10 3rd day: 0.0±0.0
4th day: 0.1±0.3
Mean age: 5th day: 0.3±0.7
40.4±16.0 6th day: 0.1±0.3
7th day: 0.4±1.0
Sharma et al. 2019 India Control group Post-operative pain Choukroun et al. Not Cited VAS CollaCote® and PRF
(17) collagen dressing VAS 2000 Control group palatal bandages
Randomized CollaCote® Day 0: 1.5±1.179 significantly accelerate
controlled 7, 12, 18, 24 and 30 7th day: 3.2±1.814 palatal wound healing
clinical trial N = 10 post-operative days 12th day: 1.5±1.65 and reduce the patient’s

e197
18th day: 0.6±0.699 pain and discomfort.
Mean age: not 24th day: 0.5±0.707
cited Complete wound 30th day: 0.1±0.316
epithelization Test Group
Test group: (H2O2-bubbling) Day 0: 2.2±2.15
PRF Weeks 1, 2, 3 and 4 7th day: 1.9±1.101
12th day: 0.8±0.789
N= 10 18th day: 0.3±0.483
24th day: 0.4± 0.699
Mean age: Not 30th day: 0.1±0.316
cited Complete wound epitheli-
alization
(H2O2-bubbling)
Control group 1
1st week: 5±0
2nd week:4.5±0.85
3rd week: 2.7±1.075
4th week: 0.2±1.636
Control group 2
1st week: 5±0
2nd week: 4.3±0.843
3rd week: 2.7±2.003
4th week: 0.1±0.316
PRF and palatal wound healing
J Clin Exp Dent. 2021;13(2):e190-200. PRF and palatal wound healing

Fig. 3: (A) Florest plot. Comparison of studies assessing the discomfort; (B) Funnel plot to evaluate
the risk of bias.

Fig. 4: (A) Florest plot. Comparison of studies assessing the complete re-epithelialization of the
palatal wound after 14 days; (B) Funnel plot to evaluate the risk of bias.

e198
J Clin Exp Dent. 2021;13(2):e190-200. PRF and palatal wound healing

Discussion the processes of angiogenesis and secretion of collagen

Normally, complete healing of any wound follows four begin (26).
overlapping phases: hemostasis, inflammation, prolife- Even faced by these extensive positive features over re-
ration, and remodeling (8). These phases are dependent pair, one of the studies included in this systematic re-
of accurate events involving mediators and signals, gui- view reported no reduction of the postoperative pain in
ding specific cells to perform their functions (8). As a the group treated with PRF (18). VAS tends to present a
cascade, these steps must follow a chronologic order, wide variety of uniform results, and, therefore, although
and, therefore, the first phase plays a determinant role for a valid method, it has limitations (27). Another topic that
the completion of wound healing. Platelets are shown as might be highlighted with regard to the biases in posto-
essential cytoplasmatic acellular fragments (19) to regu- perative pain is the difference of prescription protocols
late the homeostasis phase through vascular obliteration adopted by the studies included in the present systematic
and facilitated fibrin clot formation (20). Thus, platelet review, once each medication can act directly on pain
concentrates such as PRF may show additional benefits modulation.
on wound healing, and, because of that has been recom- Literature reports distinct centrifugation protocols for
mended for use as a bandage to cover palatal donor sites obtention of PRF. Kulkarni et al. (28) and Dohan et al.
of FGG, possibly related to improvements on postope- (22) demonstrated the same methodology for prepara-
rative pain and accelerated repair of the wound. Faced tion of the PRF (centrifuged 10mL of blood for each
with the results of the present systematic review and me- tube, at 3,000 rpm for 10 minutes). Ustaoglu et al. (18)
ta-analysis, it can be stated that the hypothesis of PRF used as test group the protocol for obtention of T-PRF
improving healing and reducing pain was confirmed. described by Tunali et al. (29) (centrifuged 10mL of
In the present research, the qualitative and meta-analyti- blood for each titanium tube, at 2.800 rpm for 12 mi-
cal (VAS = 34.84, P < 0.01 e CWE= 5.05, P<0.01) as- nutes). Tunali et al. (29) attest that the use of titanium
sessments corroborated with regard to both VAS and tubes suppresses the negative effects caused by dry
complete wound epithelialization, since they converged glass or glass-coated plastic tube. Also, titanium-activa-
to reduced postoperative pain and a higher number of ted platelet aggregation seems to present firmer network
patients with complete wound closure in groups treated structure and longer in vivo resolution time than the ones
with PRF when compared with their respective controls, formed on glass (29).
mainly 2 weeks postoperatively. These results are in Not only modifications to the tubes are reported in the li-
agreement with the systematic review of Miron et al. terature. Also, alterations on the rotation speed and time
2017 (8), which concluded that the literature supports of centrifugation incorporated other options to the li-
soft tissue regeneration following soft tissue regenerati- neage of platelet concentrates. Fujioka-Kobayashi et al.
ve procedures with PRF. (30) described the L-PRF (centrifuged 10mL of blood
Improvements provided by PRF may be associated to for each tube, at 2,700 rpm for 12 minutes), A-PRF (cen-
different paths. More than the physical property of a trifuged 10mL of blood for each tube, at 1,300 rpm for
plug during hemostasis, platelets are capable of stimu- 14 minutes), and A-PRF+ (centrifuged 10mL of blood
lating proliferation and activation of cells closely invol- for each tube, at 1,300 rpm for 8 minutes). The positive
ved with the repair process, such as fibroblasts, neutro- results of these protocols with regard to the release of
phils, macrophages, and mesenchymal stem cells (21). growth factors (30) encourage the assessment of their
The completion of the repair process is dependent on effects on pre-clinical and clinical scenarios.
platelet-specific and non-specific proteins (22), growth The use of any of the blood derivate depends on the
factors such as platelet-derived growth factor (PDGF), compliance of the patient, so, individuals who are afraid
coagulation factors, adhesion molecules, cytokines/che- of needles preclude this procedure. Even with the limi-
mokines, and angiogenic factors, all of them released tations assigned to platelet concentrates, some non-bio-
and activated by platelets (21). Moreover, among the logical advantages shall be emphasized about PRF. The
cells related to wound healing, neutrophils and macro- protocol for preparation of this specific product may be
phages also play the role of prevention of infection (23). considered of low-cost and easy to perform. Furthermo-
In the early stages of inflammation, both are involved re, PRF doesn’t require biochemical manipulation of the
with the removal of debris and necrotic tissue, thereby blood samples.
preventing microbial contamination (24). Despite the consistency and strength of the qualitative
Another important component of the PRFs is the fibrin. outcomes, the absence of standardized control group
It is a bridging molecule that supplies a tridimensio- among studies could represent a limitation of the quan-
nal matrix in which cells related with wound closure titative analysis while comparing results. Hence, the
may proliferate, organize, and play their respective positive results obtained with PRF presented by this me-
roles (25). Fibroblasts and endothelial cells permeate ta-analysis shall be interpreted embracing this situation.
within this fibrin network, and once they are arranged, Further randomized clinical trials adopting standardized

e199
J Clin Exp Dent. 2021;13(2):e190-200. PRF and palatal wound healing

control groups of palatal wound healing might be carried for wound healing: A randomized clinical control trial. Indian J Dent
in order to provide substantial data for confirmation of Res. 2019;30:991-8.
18. Ustaoğlu G, Ercan E, Tunali M. The Role of Titanium-Prepared
the effectiveness of PRF, and to increase the number and Platelet-Rich Fibrin in Palatal Mucosal Wound Healing and Histocon-
reliability of assessments evaluating this treatment. duction. Acta Odontol Scand. 2016;74:558-64.
Within the limits of the present research, the qualitative 19. Cimmino G, Golino P. Platelet biology and receptor pathways. J
synthesis of six studies combined with the meta-analy- Cardiovasc Transl Res. 2013;6:299-309.
20. Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res.
sis of two studies evaluating pain and two studies eva- 2010;89:219-29.
luating complete wound epithelialization infers that the 21. Nurden AT. Platelets, inflammation and tissue regeneration.
use of PRF reduces the postoperative pain and induces Thromb Haemost. 2011;105:S13-33.
earlier epithelialization of the palatal donor site of FGG. 22. Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi
J, et al. Platelet-rich fibrin (PRF): a second-generation platelet con-
  centrate. Part II: platelet-related biologic features. Oral Surg Oral Med
References Oral Pathol Oral Radiol Endod. 2006;101:e45-50.
1. Merijohn GK. Management and prevention of gingival recession. 23. Adamson R. Role of macrophages in normal wound healing: an
Periodontol 2000. 2016;71:228-42. overview. J Wound Care. 2009;18:349-51.
2. Sullivan HC, Atkins JH. Free autogenous gingival grafts. 3. Utili- 24. Calvin M. Cutaneous wound repair. Wounds. 1998;10:12-32.
zation of grafts in the treatment of gingival recession. Periodontics. 25. Laurens N, Koolwijk P, de Maat MP. Fibrin structure and wound
1968;6:152-60. healing. J Thromb Haemost. 2006;4:932-39.
3. Novaes AB Jr, Palioto DB. Experimental and clinical studies on 26. Gassling VL, Açil Y, Springer IN, Hubert N, Wiltfang J. Plate-
plastic periodontal procedures. Periodontol 2000. 2019;79:56-80. let-rich plasma and platelet- rich fibrin in human cell culture. Oral Surg
4. İşler SC, Uraz A, Şengül J, Çakiroğlu M, Bakırarar B, Çetiner D. Oral Med Oral Pathol Oral Radiol Endod. 2009;108:48-55.
Evalution of the patiens oral health related quality of life after harves- 27. Reed MD, Van Nostran W. Assessing pain intensity with the visual
ting free gingival graft. Cumhuriyet Dent J. 2019;22:11-21. analog scale: a plea for uniformity. J Clin Pharmacol. 2014;54:241-44.
5. Farnoush A. Techniques for the protection and coverage of the do- 28. Kulkarni MR, Thomas BS, Varghese JM, Bhat GS. Platelet-rich fi-
nor sites in free soft tissue grafts. J Periodontol. 1978;49:403-5. brin as an adjunct to palatal wound healing after harvesting a free gin-
6. Isler SC, Uraz A, Guler B, Ozdemir Y, Cula S, Cetiner D. Effects gival graft: A case series. J Indian Soc Periodontol. 2014;18:399-402.
of laser photobiomodulation and ozone therapy on palatal epithe- 29. Tunalı M, Özdemir H, Küçükodacı Z, Akman S, Fıratlı E. In vivo
lial wound healing and patient morbidity. Photomed Laser Surg. evaluation of titanium-prepared platelet-rich fibrin (T-PRF): a new
2018;36:571-80. platelet concentrate. Br J Oral Maxillofac Surg. 2013;51:438-43.
7. Samani MK, Saberi BV, Ali Tabatabaei SM, Moghadam MG. The 30. Fujioka-Kobayashi M, Miron RJ, Hernandez M, Kandalam U,
clinical evaluation of platelet rich plasma on free gingival graft’s donor Zhang Y, Choukroun J. Optimized Platelet-Rich Fibrin with the Low-
site wound healing. Eur J Dent. 2017;11:447-54. Speed Concept: Growth Factor Release, Biocompatibility, and Cellu-
8. Miron RJ, Fujioka-Kobayashi M, Bishara M, Zhang Y, Hernandez lar Response. J Periodontol. 2017;88:112-21.
M, Choukroun J. Platelet-rich fibrin and soft tissue wound healing: a
systematic review. Tissue Eng Part B Rev. 2017;23:83-99. Ethics approval
9. Feigin K, Shope B. Use of Platelet-Rich Plasma and Platelet-Rich Not applicable.
Fibrin in Dentistry and Oral Surgery: Introduction and Review of the
Literature. J Vet Dent. 2019;36:109-23 Human and animal rights
10. Ozcan M, Ucak O, Alkaya B, Keceli S, Seydaoglu G, Haytac MC. No human or animal were used in this study.
Effects of platelet-rich fibrin on palatal wound healing after free gin-
gival graft harvesting: a comparative randomized controlled clinical Consent for publication
trial. Int J Periodontics Restorative Dent. 2017;37:e270-8. Not applicable.
11. Bahammam MA. Effect of platelet rich fibrin palatal on pain scores
and wound healing after free gingival graft: a randomized controlled Funding
clinical trial. Clin Oral Investig. 2018;22:3179-88. This research received no external funding.
12. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Pre-
ferred reporting items for systematic reviews and meta-analyses: the Conflicts of Interest
PRISMA statement. Int J Surg. 2010;8:336-41. The authors declare no conflict of interest, financial or otherwise.
13. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman
AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias
in randomised trials. BMJ. 2011;343:1-9.
14. de Souza Batista VE, Vechiato-Filho AJ, Santiago JF Jr, Sonego
MV, Verri FR, Dos Santos DM, et al. Clinical viability of single im-
plant-retained mandibular overdentures: a systematic review and me-
ta-analysis. Int J Oral Maxillofac Surg. 2018;47:1166-77.
15. Lektemur Alpan A, Torumtay Cin G. PRF improves wound healing
and postoperative discomfort after harvesting subepithelial connective
tissue graft from palate: a randomized controlled trial. Clin Oral Inves-
tig. 2019;24:425-36.
16. Femminella B, Iaconi MC, Di Tullio M, Romano L, Sinjari B,
D’arcangelo C, et al. Clinical comparison of platelet-rich fibrin and a
gelatin sponge in the management of palatal wounds after epitheliali-
zed free gingival graft harvest: a randomized clinical trial. J Periodon-
tol. 2016;87:103-13.
17. Sharma V, Kumar A, Puri K, Bansal M, Khatri M. Application of
platelet rich fibrin membrane and collagen dressing as palatal bandage

e200