The Saudi Journal for Dental Research (2014) 5, 117122

King Saud University

The Saudi Journal for Dental Research

www.ksu.edu.sa
www.sciencedirect.com

REVIEW ARTICLE

Platelet-rich brin: Its role in periodontal

regeneration
Preeja Chandran

a,*

, Arun Sivadas

Department of Periodontics, PMS College of Dental Science & Research, Golden Hills, Vattappara, Venkode (PO),
Thiruvananthapuram 695028, Kerala, India
b
Kerala Institute of Medical Sciences, Thiruvananthapuram 695029, Kerala, India
Received 18 June 2013; revised 7 September 2013; accepted 7 September 2013
Available online 20 October 2013

KEYWORDS
Platelet-rich brin;
Platelet-rich plasma;
Regeneration;
Tissue engineering;
Growth factors

Abstract Platelets can play a crucial role in periodontal regeneration as they are reservoirs of
growth factors and cytokines which are the key factors for regeneration of the bone and maturation
of the soft tissue. Platelet-rich plasma (PRP) and platelet-rich brin (PRF) are autologous platelet
concentrates prepared from patients own blood. Recent researches are being focused on the development of therapeutic alternatives which are easy to prepare, non-toxic or biocompatible to living
tissues and economically cheap that might result in the local release of growth factors accelerating
hard and soft tissue healing. PRF is a natural brin-based biomaterial prepared from an anticoagulant-free blood harvest without any articial biochemical modication that allows obtaining brin
membranes enriched with platelets and growth factors. Evidence from the literature suggests the
potential role of PRF in periodontal regeneration and tissue engineering. The slow polymerization
during centrifugation and brin-based structure makes PRF a better healing biomaterial than PRP
and other brin adhesives. The main aim of this review article is to briey describe the novel platelet
concentrate PRF and its potential role in periodontal regeneration.
2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.

Contents
1.
2.
3.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Role of platelets in periodontal wound healing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
What is PRF? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

* Corresponding author. Tel.: +91 9447492992; fax: +91 472 258

7874.
E-mail address: drpreeja@gmail.com (Preeja C.).
Peer review under responsibility of King Saud University.

Production and hosting by Elsevier

2352-0035 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.
http://dx.doi.org/10.1016/j.ksujds.2013.09.001

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4.
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9.
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11.
12.

Historical background . . . . . . . . . . . . . . . . . . . . . . . . . . .
Potential benets of using PRF in periodontal regeneration
Protocol for preparation of PRF . . . . . . . . . . . . . . . . . . .
Clinical applications . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Evidence for the role of PRF in periodontal regeneration . .
Evidence for the role of PRF in tissue engineering . . . . . . .
Drawbacks of PRF . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction
Periodontal disease is dened as a complex, multifactorial disease characterized by the loss of connective tissue attachment
with destruction of periodontal tissues. The aim of periodontal
therapy is to eliminate inammatory process, prevent the progression of periodontal disease and also to regenerate the lost
periodontal tissues. Periodontal regeneration is a complex
multifactorial process involving biologic events like cell adhesion, migration, proliferation, and differentiation in an orchestrated sequence.1 Periodontal regenerative procedures include
soft tissue grafts, bone grafts, root biomodications, guided
tissue regeneration, and combinations of these procedures.2
The current perspective is that regenerative periodontal therapies to date can only restore a fraction of the original tissue
volume 2 and have a limited potential in attaining complete
periodontal restoration.3 Various biomaterials have been used
for periodontal tissue regeneration in addition to autogenous
and allogenic bone grafts but not a single graft material is considered as gold standard for the treatment of intrabony defects.
Periodontal wound healing requires a sequence of interactions between epithelial cells, gingival broblasts, periodontal
ligament cells, and osteoblasts. The disruption of vasculature

Preeja C, Arun S
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during wound healing leads to brin formation, platelet aggregation, and release of several growth factors into tissues from
platelets4 through molecular signals which are primarily mediated by cytokines and growth factors. There is evidence that
the presence of growth factors and cytokines in platelets play
key roles in inammation and wound healing.5 Platelets also
secrete brin, bronectin, and vitronectin, which act as a matrix for the connective tissue and as adhesion molecules for
more efcient cell migration.6 This has led to the idea of using
platelets as therapeutic tools to improve tissue repair particularly in periodontal wound healing.
Platelet-rich brin (PRF) described by Choukroun et al.7 is
a second-generation platelet concentrate which contains platelets and growth factors in the form of brin membranes prepared from the patients own blood free of any anticoagulant
or other articial biochemical modications. The PRF clot
forms a strong natural brin matrix, which concentrates almost all the platelets and growth factors of the blood harvest8,9
and shows a complex architecture as a healing matrix with unique mechanical properties which makes it distinct from other
platelet concentrates. PRF enhances wound healing and regeneration and several studies show rapid and accelerated wound
healing with the use of PRF than without it.10,11 PRF is superior to other platelet concentrates like PRP due to its ease and
inexpensive method of preparation and also it does not need
any addition of exogenous compounds like bovine thrombin
and calcium chloride. It is advantageous than autogenous graft
also because an autograft requires a second surgical site and
procedure. Thus PRF has emerged as one of the promising
regenerative materials in the eld of periodontics. This review
article explains the novel platelet concentrate PRF, its preparation, clinical applications and benets and drawbacks over
other biomaterials.
2. Role of platelets in periodontal wound healing

Figure 1 Test tube showing platelet-rich brin after centrifugation of blood.

Platelets play a key role in wound healing and hence wound

healing after periodontal treatment can be accelerated by the
use of platelet concentrates. The wound healing process initiated by the formation of blood clot and after tissue injury in
periodontal surgery causes adherence and aggregation of
platelets favoring the formation of thrombin and brin. In
addition, there is release of certain substances from platelets
that promote tissue repair, angiogenesis, inammation and immune response. Platelets also contain biologically active
proteins and the binding of these secreted proteins within a

Platelet-rich brin: Its role in periodontal regeneration

developing brin mesh or to the extracellular matrix can create
chemotactic gradients favoring the recruitment of the stem
cells, stimulating cell migration, differentiation, and promoting
repair. Thus the use of autologous platelet concentrates is a
promising application in the eld of periodontal regeneration
and can be used in clinical situations requiring rapid healing.
3. What is PRF?
PRF (platelet rich brin) was rst developed in France for use
in the eld of oral and maxillofacial surgery.7 Choukrouns
platelet-rich brin (PRF) is a leukocyte and platelet rich brin
biomaterial12 with a specic composition and three-dimensional architecture. PRF is classied as a second generation
platelet concentrate as it is prepared as a natural concentrate
without the addition of any anticoagulants.13,14 PRF is often
called Choukrouns PRF as there are other platelet concentrates with similar names such as Vivostat PRF (considered
a pure platelet-rich plasma) or Fibrinet PRF (without leukocytes). PRF has a dense brin network with leukocytes, cytokines, structural glycoproteins15 and also growth factors such
as transforming growth factor b1, platelet-derived growth factor, vascular endothelial growth factor and glycoproteins such
as thrombospondin-1 during P7 day.16 Leukocytes that are
concentrated in PRF scaffold play an important role in growth
factor release,16 immune regulation,9 anti-infectious activities,17 and matrix remodeling during wound healing. The slow
polymerization mode of PRF and cicatricial capacity creates a
physiologic architecture favorable for wound healing.18
4. Historical background
Platelets are used as powerful tools for periodontal regeneration
for the past two decades due to the key role of platelets in wound
healing process. Although the use of brin adhesives is well documented from the past 30 years19,20 their use is still controversial

Figure 2

Platelet-rich brin after centrifugation.

119
due to the complexity in preparation and risk of cross-infection.
After that concentrated platelet-rich plasma (cPRP) was developed with a less complex production protocol. It is prepared
from the patients own blood and is activated by the addition
of thrombin and calcium. The structure consists of a three
dimensional biocompatible brin scaffold with a limited volume
of plasma enriched in platelets. When PRP is activated the
growth factors and proteins are released to the local environment accelerating postoperative wound healing and tissue repair.18 But the disadvantage of using PRP is that its properties
can vary depending on the concentration of platelets, amount
of leukocytes, the type of activator used and time of placement
of brin scaffold after clotting. But there are certain risks associated with the use of PRP.21 The presence of bovine thrombin
in PRP can result in the development of antibodies to the clotting
factors V, XI and thrombin which can adversely affect the coagulation process. In addition, bovine thrombin preparations contain clotting factor V which can result in immune system
activation when challenged with a foreign protein. Other drawbacks about the use of PRP include legal restrictions on handling
the blood and also controversies in the literature regarding the
benets and clinical outcome of use of PRP. All these have led
to the generation of a new family of platelet concentrate called
platelet-rich brin which overcomes many of the limitations of
PRP. PRF is a potent autologous regenerative material with
many clinical applications in the eld of periodontics as it accelerates both soft tissue and hard tissue healing.
5. Potential benets of using PRF in periodontal regeneration
Platelet-rich brin is a second generation platelet concentrate
which can enhance both soft and hard tissue healing. Its advantages over platelet-rich plasma include ease of preparation, ease of
application, minimal expense, and lack of biochemical modication (no bovine thrombin or anticoagulant is required). This considerably reduces the biochemical handling of blood as well as
risks associated with the use of bovine-derived thrombin. PRF
also contains physiologically available thrombin that results in
slow polymerization of brinogen into brin which results in a
physiologic architecture that is favorable to wound healing.
The cytokines which are present in platelet concentrates
play an important role in wound healing. The structural

Figure 3

Platelet-rich brin after collection.

120
conguration of PRF with respect to cytokine incorporation in
brin meshes is different from that present in PRP. The natural
polymerization in PRF results in increased incorporation of the
circulating cytokines in the brin meshes (intrinsic cytokines).
These intrinsic cytokines will be having an increased lifespan
and they will be released and used only at the time of initial cicatricial matrix remodeling which creates a long term effect. In
PRP and other brin adhesives the presence of articial additives like bovine thrombin and calcium chloride results in sudden
brin polymerization causing loss of synergy between cytokines
and brin with faster physiologic elimination of these cytokines.
The three dimensional organization of a brin network in PRF
and PRP affects the biologic and mechanical properties of these
platelet concentrates. During gelling of these brin structures,
the brin brillae can be assembled in 2 ways, bilateral junctions
or equilateral junctions. In PRP there are bilateral junctions with
strong thrombin concentrations that allow thickening of brin
polymer with a rigid network resulting in poor cytokine entrapment and cellular migration. But in PRF the equilateral junctions
are present with weak thrombin concentrations forming a ne
and exible brin network which is more elastic in nature favoring
cytokine entrapment and cellular migration.8 All these comparative parameters make PRF a better healing biomaterial than PRP
and other brin adhesives.
Another added advantage of PRF is the presence of natural
brin network in PRF which protects the growth factors from
proteolysis.12,22 PRF also favors the development of microvascularization leading to a more efcient cell migration.
6. Protocol for preparation of PRF
The classical technique for PRF preparation was invented by
Dr. Choukroun7 in 2000. It is the current PRF technique
authorized by the French Health Ministry in which PRF is
prepared without using an anticoagulant during blood harvesting or bovine thrombin during gelling.6
A standard protocol for PRF preparation should be
followed to obtain proper quantity and quality of the brin
matrix, leukocytes, platelets, and growth factors. The equipment required for PRF preparation includes a PC-02 table centrifuge and a blood collection kit consisting of a 24 gauge
buttery needle and 9 ml blood collection tubes. A sample of
blood is collected from patient without anticoagulant in
10 ml tubes which are immediately centrifuged at a rate of
3000 rpm for 10 min. During the centrifugation process, when
the blood gets in contact with the test tube wall the platelet gets
activated leading to the initiation of coagulation cascade. After
centrifugation, the resultant product consists of three layers.
The topmost layer consisting of acellular PPP (platelet poor
plasma), PRF clot in the middle and RBCs at the bottom of
the test tube (see Fig. 1). The brin clot obtained after centrifugation is removed from the tube and the attached red blood
cells scraped off from it and discarded (see Fig. 2). PRF can
also be prepared in the form of a membrane by squeezing
out the uids present in the brin clot.
The duration of time between blood collection and centrifugation process is an important parameter affecting the success
and clinical outcome of this procedure. The slow handling of
blood to centrifugation process will result in diffuse polymerization of brin leading to the formation of a small blood clot with
irregular consistency. Hence a reproducible protocol for PRF

Preeja C, Arun S
production should be followed to obtain a clinically usable brin
clot with massive enmeshment of platelets (see Fig. 3).
7. Clinical applications
PRF is a powerful healing biomaterial with inherent regenerative capacity and can be used in various procedures such as for
the treatment of periodontal intrabony defects,10,11 treatment
of furcation,23 sinus lift procedures24 and as a scaffold for human periosteal cells in vitro, which nds application in the eld
of tissue engineering.25
8. Evidence for the role of PRF in periodontal regeneration
PRF is enriched with platelets, growth factors and cytokines
increasing the healing potential of both hard and soft tissue.4,5
There are only a few references in the literature about the biologic
properties of PRF when compared to other platelet concentrates.
The literature mostly contains animal and human studies of the
experimental use of PRF and only limited in vitro studies have
been carried out on the effects of PRF on cell proliferation. Inspite
of the lack of scientically proven clinical benets, PRF is considered as a healing biomaterial and is commonly used in implant
and plastic periodontal surgery procedures to enhance bone
regeneration and soft-tissue wound healing.26,27 According to
Choukron et al. PRF was initially used in implant surgery to enhance the healing properties of the bone.7 PRF can promote the
healing of osseous defects by the following mechanisms. According to Chang et al. PRF promotes the expression of phosphorylated extracellular signal-regulated protein kinase (p-ERK) and
stimulates the production of osteoprotegerin (OPG) which inturn
causes proliferation of osteoblasts.28 Another study by Huang
et al. reported that PRF stimulates the osteogenic differentiation
of the human dental pulp cells by upregulating osteoprotegerin
and alkaline phosphatase expression.29 PRF also releases growth
factors such as platelet-derived growth factor and transforming
growth factor which promote periodontal regeneration.8,9 Chang
et al. in a study reported that PRF stimulates cell proliferation in a
specic manner.30 PRF induces cell proliferation of osteoblasts,
periodontal ligament cells and growth factors during a 3-day culture period and suppressed oral epithelial cell growth. These cell
type-specic actions may be benecial for periodontal regeneration. Diss et al. in a 1 year prospective study on osteotome sinus
oor elevation using Choukrouns platelet-rich brin grafting
material clearly demonstrated that brin matrix of PRF directly
promotes angiogenesis.31 PRF when used as a membrane for
guided tissue regeneration as a grafting material creates an improved spacemaking effect which facilitates cell events that are
favorable for periodontal regeneration leading to mineralized tissue formation. PRF is having an inherent osteoconductive and/or
osteoinductive property which is benecial for regeneration of the
bone. Sanchez et al. in an experimental study compared the inuence of PRP and PRF on proliferation and differentiation of osteoblasts and he reported that the afnity of osteoblasts to the PRF
membrane appeared to be superior than the afnity of osteoblasts
to PRP.21 Sharma et al. conducted a randomized controlled clinical trial for the treatment of 3-wall intrabony defects in chronic
periodontitis patients with plateletrich brin and reported a statistically signicant improvement in pocket depth reduction and
bone ll in test group than in controls.10 A similar study was conducted for the treatment of mandibular degree II furcation defects

Platelet-rich brin: Its role in periodontal regeneration

with plateletrich brin and showed a signicant improvement in
pocket depth reduction, gain in clinical attachment level and bone
ll in test group when compared to controls.23 Thorat et al. investigated the clinical and radiological effectiveness of autologous
PRF in the treatment of intrabony defects of chronic periodontitis
patients and reported a greater reduction in pocket depth, more
gain in clinical attachment level and greater intrabony defect ll
at sites treated with PRF than those treated with open ap
debridement alone.11 Another randomized controlled clinical
trial was done in three treatment groups comprising of OFD
(open ap debridement) + PRF, OFD + PRF + HA (porous
hydroxyapatite graft) and OFD alone as control. This study
showed a signicant bone ll in plateletrich brin treated group
than in controls and a signicant bone ll and gain in clinical
attachment level in plateletrich brin combined with porous
hydroxyapatite graft than in control group.32 A comparative evaluation between platelet-rich brin and platelet-rich plasma for the
treatment of three-wall intrabony defects was done and showed a
greater bone ll in PRF treated group than in PRP treated
group.33 The effect of platelet-rich brin on human periodontal
ligament broblasts and application in periodontal infrabony defects was studied by Chang et al. and reported that PRF was
found to increase extracellular signal-regulated protein kinase
phosphorylation and osteoprotegerin in periodontal ligament
broblasts and upregulation of alkaline phosphatase activity.
Also, infrabony defects exhibited pocket reduction and clinical
attachment gain after six months with bone ll in defects.34
9. Evidence for the role of PRF in tissue engineering
The a-granules present in platelets contain growth factors like
platelet derived factor (PDGF), transforming growth factor-b
(TGF-b), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF).35 Platelet derived growth factor
(PDGF) has an important role in periodontal regeneration
and wound healing36 and receptor for PDGF is present on gingiva, periodontal ligament and cementum and it activates broblasts and osteoblasts promoting protein synthesis37 PDGF also
functions as a chemoattractant for broblasts and osteoblasts in
gingiva and periodontal ligament resulting in their activation.38
PRF promotes angiogenesis because as it has low thrombin level optimal for the migration of endothelial cells and broblasts.
PRF entraps circulating stem cells due to its unique brin structure. This property of PRF nds application in healing of large
osseous defects where there is migration of stem cells differentiating into osteoblast phenotype.26 PRF also helps in facilitating
adhesion and spreading of cells, regulates gene expression of
growth factors, growth factor receptors, proteins, and determines the outcome of a cells response to growth factors due
to the presence of collagen, bronectin, elastin, other non-collagenous proteins, and proteoglycan in the extracellulat matrix
of PRF.39 The use of PRF as a tissue engineering scaffold
was investigated by many researchers for the past few years.
In a study by Gassling et al. reported that PRF appears to be
superior to collagen as a scaffold for human periosteal cell proliferation and PRF membranes can be used for in vitro cultivation of periosteal cells for bone tissue engineering.25 PRF has
immune functions like chemotaxis as leukocytes present in
PRF degranulates during activation and releases cytokines like
IL-1, IL-4, IL-6 and TNF-a. PRF also contains anti-inammatory cykokine such as IL-4 which requires further research.9

121
Thus PRF is a potential tool in tissue engineering but clinical
aspects of PRF in this eld requires further investigation.
10. Drawbacks of PRF
The main shortcoming of PRF is its preparation and storage.
The clinical benet of PRF depends on time interval between
speed of handling between blood collection and centrifugation
as PRF is prepared without any addition anticoagulants.
Another main disadvantage of PRF is its storage after
preparation.40 Also PRF membranes should be used immediately after preparation as it will shrink resulting in dehydration
altering the structural integrity of PRF. Dehydration also results
in the decreased growth factor content in PRF16 and leukocyte
viability will be adversely affected altering its biologic properties. PRF when stored in refrigerator can result in risk of bacterial contamination of the membranes. These limitations with the
use of PRF can be circumvented by sticking onto a standard protocol for preparation and preservation.
11. Future directions
In the future more studies should be carried out to correlate
the clinical outcome of PRF with its biologic mechanisms
which opens novel applications of this autologous platelet
concentrate. There are only limited studies in the literature
on the effect of PRF on cell proliferation and other biologic
effects. Therefore, more studies should be conducted which
open newer strategies for the use of this platelet concentrate.
12. Conclusion
PRF by Choukrouns technique is a simple and inexpensive
technique for the successful regeneration of periodontal
tissues. The main advantage is that PRF preparation utilizes
the patients own blood reducing or eliminating disease
transmission through blood. In the future more studies and
clinical trials are needed to investigate potential applications
of PRF in the eld of periodontal regeneration and tissue
engineering and to extend its clinical applications.
Conict of interest
The author declared that there is no conict of interest.
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