Platelet Rich Fibrin (PRF) in Dentistry, What is PRF ? , What are the difference between PRP,PRGF and PRF ?, Preparation of PRF , shapes of PRF, Role of PRF in wound healing, APPLICATIONS OF PRF, Applications of PRF In Oral and Maxillofacial Surgery, Applications of PRF In Periodontics, Applications of PRF In Endodontics, Applications of PRF In Tissue Engineering
2. Introduction
The conception of healing process is still partial and is a keen subject for
research, but it is well known that platelets play a significant role in both
hemostasis and wound healing activity . There is corroboration on the
fact that platelets play a crucial role in tissue healing and inflammation
.The presence of growth factors and cytokines are important guidelines
to regenerate the wound area . Upon the activation of platelets there is
proof of release of not only cytokines, enzymes, proteins but also
fibrinolytic and anti-fibrinolytic proteins, which act as a matrix during the
pathway of tissue repair. This has led to the notion in the use of platelets
as a remedial tool to improve tissue healing.
3. Introduction
The world of dentistry was first familiarized with the regenerative capacity of
platelets in the 70s. it is a preparation of platelets present in a small volume of
plasma containing a large amount of growth factors (GFs), which is essential
for bone growth and regeneration . Platelet-rich fibrin (PRF) is frequently
named as Choukroun’s PRF after its inventor, and was described as a second-
generation platelet concentrate which contains platelets and growth factors in
the form of fibrin membranes prepared from the patient’s own blood free of
any anticoagulant or other artificial biochemical modifications .
4. What is PRF ?
Platelet rich fibrin (PRF) is a fibrin matrix in which platelet cytokines, growth
factors and cells are trapped and may be released after a certain time and
that can serve as a resorbable membrane. It can be obtained from blood
with the help of a simple process. PRF is basically a concentrate of growth
factors that promote wound healing and regeneration which is used in
various disciplines of dentistry to repair various lesions and regenerate
dental and oral tissues.
PRF was developed in France by Joseph Choukroun et al.in 2001.
5. What is PRF ?
They used PRF to improve bone healing in cases of implants. It is a fibrin
matrix in which platelet cytokines, growth factors and cells are trapped
and may be released after a certain time and that can serve as a
resorbable membrane. Growth factors are released after activation from
the platelets trapped within fibrin matrix, and have been shown to
stimulate the mitogenic response in the periosteum for bone repair
during normal wound healing.
6. What is PRF ?
PRF is an autogenous osteoinductive material that enhances
osteogenesis in the extraction tooth socket in comparison to the
physiological healing process. It is an optimized blood clot. It also
provides a significant postoperative protection of the surgical site and
seems to accelerate the integration and remodeling of the grafted
biomaterial .
7. What is PRF ?
Main elements of PRF
FIBRIN:
SUPPORTING
MATRIX
PLATELETS:
RICH IN GROWTH
FACTORS
LEUKOCYTES : STEM CELLS
ANTIBACTERIAL, NEOVASCULARISATION
AND REGENERATIVE PROPERTIES
8. What are the difference between
PRP,PRGF and PRF ?
Platelet Rich Plasma (PRP): The Platelet-Rich Plasma is a product derived from blood,
its characteristic is due to the fact that the platelets present in the PRP release numerous
substances that promote tissue repair and affect the behavior of other cells by modulating the
inflammation and the formation of new blood vessels.
Despite the growing success and use of PRP in the initial years following its launch, there
were several reported limitations that prevented its full potential. The technique itself was
lengthy and therefore required the additional use of anti-coagulant factors to prevent
clotting using bovine thrombin or CaCl2, both known inhibitors of wound healing. These
drawbacks in combination with the lengthy harvesting/centrifugation preparation times
were then frequently being utilized in large maxillofacial surgeries, whereas the typical dental
or medical practitioner was resistant to its use due to lengthy preparation times.
9. What are the difference between
PRP,PRGF and PRF ?
Platelet Rich Plasma (PRP):
One of the other drawbacks of PRP was the fact that it was liquid by nature, and therefore
required its combination with other biomaterials including bone grafts derived from human
cadavers (allografts) or animal products (xenografts), thereby further combining its use with
other “unnatural” products.
10. What are the difference between
PRP,PRGF and PRF ?
Platelet Rich Plasma (PRGF): is a type of plasma enriched of proteins and
circulating growth factors able to aid the bone and soft tissue regeneration. PRGF
contains many different cells and cell-types highly concentrated in a gelatinous
form which can be placed into the site of the injury: these cells stimulate and
accelerate the healing process by forming blood clots and releasing growth factors
into the wound.
1. PRGF does not need bovine or human thrombin for coagulation; PRGF includes
plasma proteins and coagulative factors and is then more advantageous
compared to PRP.
11. What are the difference between
PRP,PRGF and PRF ?
2 . PRGF preparation was carried out by following a previously described protocol.
Blood sample was obtained from basilica vein using a large needle to avoid platelet
rupture. Sampled blood was combined with anticoagulant (1 ml of 3.8% sodium citrate
for 10 ml blood) and centrifuged at 460 G in 8 minutes: after the centrifugation, PRGF
was taken from the bottom of the tube.
3 . Calcium Chloride was then added to PRGF (0.05 ml per ml): this action promotes
the coagulation, usually obtained within at most 10 minutes. At the end of the
procedure, we obtained a gelatinous PRGF, to be immediately placed in the surgical
site.
12. What are the difference between
PRP,PRGF and PRF ?
Platelet Rich Fibrin (PRF):
is a quite modern platelet concentrate, it is achieved with a simplified preparation,
with no biochemical manipulation of blood. This technique does not require
anticoagulants or bovine thrombin (or any other gelling agent). This feature makes
this product easily usable, with a low rate of mistakes during the preparation stage.
The PRF has been studied by many research groups, and it has been shown that it
is able to stimulate osteogenesis in bone environment, in addition to angiogenesis;
Furthermore, it provides a scaffold consisting of fibrin that allows cellular migration,
and these are certainly the fundamental aspects for the process of bone
regeneration.
13. What are the difference between
PRP,PRGF and PRF ?
Following the centrifugation, the clot of PRF obtained contains:
The highest values of platelets
The highest values of the growth factors PDGF, VEGF and TGF
A share extremely representative of fibrin, fibronectin and vitronectin
About 65% of leukocytes
Important studies have found that the PRF can be a node on the local immune
regulation, with ability to show a feedback control of the local inflammation. This
notion may explain the reduction of postoperative infections when the PRF is
used as an additive surgery.
14. What are the difference between
PRP,PRGF and PRF ?
Overview table comparing the three blood products about their most important characteristics.
15. Preparation of PRF:
1. For preparation of PRF, blood sample is collected from the patient without anticoagulant using a
butterfly needle and 10 ml blood collection tubes.
2. After collection of blood, it is immediately centrifuged on a table-top centrifuge at a rate of 3000 rpm
for 10 minutes.
3. After centrifugation, 3 layers are obtained in the test tube . The topmost layer consisting of acellular
PPP (platelet poor plasma), PRF clot in the middle and RBCs at the bottom of the test tube.
4. The middle layer of PRF clot is then removed with sterile tweezers and separated from the underlying
RBC layer using scissors and then transferred on a sterile dish and stored in a refrigerator.
16. Preparation of PRF:
5. PRF membrane can be obtained by squeezing out the liquids present in the fibrin clot. Liquid removal from the
PRF fraction can be done through mechanical pressure between gauze layers resulting in a fairly solid, gel-like
material that can be used in various clinical applications as a filling material or as a suturing membrane
(A) (B) (C) (D) (E)
Preparation of platelet-rich fibrin (PRF). (A) PRF formed in the middle part of the tube. The upper part contained acellular plasma and the bottom part
contained red corpuscles. (B) PRF preparation, the red cell clot is removed by scissors ,The fibrin clot was easily separated from the lower part of the
centrifuged blood. (C) The PRF clot was gently pressed between 2 layers of sterile dry gauze to form a membrane (D),(E) PRF can be minced as a
grafting material
18. shapes of PRF:
1. RECENTLY, NUMEROUS TECHNIQUES USING BLOOD-DERIVED CONCENTRATES HAVE BEEN
DEVELOPED TO OPTIMIZE THE DIFFERENT RATIOS WITHIN THE FIBRIN MATRIX , A RECENT STUDY
SHOWED THAT SPECIFIC CELL TYPES ARE DISTRIBUTED DIFFERENTIALLY DEPENDING ON THE
(CUMULATIVE) CENTRIFUGAL FORCE (GHANAATI S ET AL 2014)
2. CHOUKROUN MODIFIED HIS PRF TO PRODUCE A-PRF (LEUKOCYTE-ENRICHED, ADVANCED TYPE)
AND I-PRF (INJECTABLE PRF) BY: REDUCING THE CENTRIFUGE SPEED LEUKOCYTE INFILTRATION INTO
THE RED BLOOD CELL FRACTION IS THEREFORE MINIMIZED (GHANAATI S ET AL 2014; CHOUKROUN J
2014)
3. BOTH A-PRF AND I-PRF PREPARATIONS ARE CHARACTERIZED BY PLATELETS, LEUKOCYTES AND
CIRCULATING STEMnCELLS, AND ENDOTHELIAL CELLS CONCENTRATED IN THEnFIBRIN CLOT
(Choukroun J 2014) LEUKOCYTES ARE ENRICHED IN A-PRF AND L-PRF (KawasenT 2015)
19. shapes of PRF:
4. IN 2006 SACCI DEVELOPED ANOTHER PREPARATION CALLED CGF (CONCENTRATED GROWTH
FACTORS) A CENTRIFUGE DEVICE THAT HAS A SPECIAL PROGRAMMED SPIN CYCLE IS USED FOR
THE PRODUCTION OF CGF (RODELLA LF ET AL 2011) THE DIFFERENT CENTRIFUGATION SPEED
PERMITS THE ISOLATION OF FIBRIN MATRIX THAT IS MARKEDLY LARGER, DENSER AND RICHER IN
GROWTH FACTORS AS COMPARED TO PRF.
20. shapes of PRF:
5. TITANIUM PRF (T-PRF): IT IS BASED ON THE HYPOTHESIS THAT TITANIUM MAY BE MORE
EFFECTIVE IN ACTIVATING PLATELETS THAN THE SILICA ACTIVATORS USED WITH GLASS TUBES
IT ELIMINATES THE SPECULATIONS ABOUT THE POTENTIAL NEGATIVE EFFECTS OF SILICA FROM DRY
GLASS OR GLASS-COATED PLASTIC TUBES.
NOTE :
T-PRF HAS A HIGHLY ORGANIZED FIBRIN
NETWORK WITH CONTINUOUS INTEGRITY
AS COMPARED TO L-PRF.
21. Role of PRF in wound healing:
Prolonged release of growth factors at the wound site
Proliferation of fibroblasts and osteoblasts
Promotes angiogenesis
Induces collagen synthesis
Guides in wound coverage
Mechanical adhesion by fibrin
Trapping of circulating stem cells
Regulation of immunity
22. APPLICATIONS OF PRF
ENDODONTICS ORAL AND
MAXILLOFACIAL SURGERY
periodontic
s
Tissue
engineering• In treatment of open
apex
For regeneration of
pulp-dentin
complex
In combination with
MTA to create root end
barriers in apexification
procedures to prevent
extrusion of material
• In regenerative
pulpotomy
• To fill in bony defect after
• Filling material in avulsion
sockets, bony defects etc.
• Bone augmentation in sinus
lifts for posterior maxilla
augmentation for implants,
bony defects etc.
• Ridge preservation
• Guided bone regeneration,
• For treatment of
intrabony defects
• For treatment of
gingival recession
• Guided tissue
regeneration
• Periapical lesions
• For in vitro cultivation of
human periosteal
cells for bone
23. Studies show that PRF can be used as filling material in extraction sockets. As a
filling material in extraction sockets, PRF will act as a stable blood clot for
neovascularization and accelerated tissue regeneration. This can be used to
improve wound healing in immunocompromised and diabetic patients. Also,
as PRF stimulates coagulation (with thrombospondin) and wound closure, it can
be used as an adjuvant in patients on anticoagulant therapy .
Applications of PRF In Oral and
Maxillofacial Surgery
24. PRF has been extensively used in sinus lift procedures. Some studies show the
use of PRF as the sole filling material during sinus lift and implantation. Some
studies show the use of PRF in combination with other bone graft materials in
various direct and indirect sinus lift techniques like bone-added sinus floor
elevation, osteotome-mediated sinus floor elevation, minimally invasive antral
membrane balloon elevation etc. Some studies also show the use of PRF in
combination with beta Tricalcium phosphate (beta TCP) without bone graft in
sinus lift procedures and chronic periodontal lesions.
Applications of PRF In Oral and
Maxillofacial Surgery
25. The filling of avulsion sockets with PRF leads to very favorable results when
bony walls are intact. A combination of PRF with bone substitutes and other
adjuncts may be necessary in residual defects where one or several walls are
missing or damaged in order to provide an adequate reconstruction of bone
volume. PRF increases the cohesion between the graft materials as fibrin act
as physiological glue between the wound tissues . Natural blood coagulation
leads to formation of a fibrin matrix that biologically links wounded tissue
together along with cell proliferation, cell migration, neomatrix apposition and
remodeling. Therefore, the combination of PRF with other graft materials
should improve the integration of graft material, since PRF is an optimized
blood clot.
Applications of PRF In Oral and
Maxillofacial Surgery
26. In cases of wide sockets and lesions where primary closure is difficult, PRF
membrane can be used as a covering and protective membrane that
promotes re-epithelialization of the site and accelerates the merging of the
wound margins. The elasticity and strength of PRF fibrin membrane makes it
easy to suture. As a membrane for guided bone regeneration (GBR), the PRF
dense matrix architecture covers, protects and stabilizes bone graft material
and operative site in general.
Applications of PRF In Oral and
Maxillofacial Surgery
27. In periodontics, PRF has been used to treat gingival recession, intra-bony defects and
periapical lesions. Some case reports show the use of a combination of PRF gel,
hydroxyapatite graft and guided tissue regeneration (GTR) membrane to treat IBD . Some
studies show the use of PRF gel and PRF membrane in combination with a bone graft for
treating a tooth with a combined periodontic-endodontic lesion . Some studies show use of
two layers of PRF membrane with to cover the defect. The membranes are very thin and
inhomogeneous and leucocytes and platelet aggregates are believed to be concentrated in
end of the membrane. Therefore, two layers of membrane in opposite sense can be used to
prevent the resorption of the thin membrane and to allow the entire surgical area to be
exposed to same components (leucocytes and platelet aggregates) . Platelet rich fibrin as a
potential novel root coverage approach has been reported by Anil kumar et al. for covering
localized gingival recession in mandibular anterior teeth using combined laterally positioned
flap technique and PRF membrane.
Applications of PRF In
Periodontics
28. 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 in turn causes
proliferation of osteoblasts. Another study by Huang et al. reported that
PRF stimulates the osteogenic differentiation of the human dental pulp
cells by up regulating osteoprotegerin and alkaline phosphatise expression.
PRF also releases growth factors such as platelet-derived growth factor
and transforming growth factor which promote periodontal lregeneration .
Applications of PRF In
Periodontics
29. Studies have shown that PRF can be used as a scaffolding material in an
infected necrotic immature tooth for pulpal regeneration and tooth
revitalization . Also, some case reports show that the combination of PRF
membrane as a matrix and MTA in apexifcation procedures prove to be an
effective alternative for creating artificial root-end barriers and to induce
faster periapical healing in cases with large periapical lesions. Use of a
membrane can prevent the extrusion of material . Use of PRF in
regenerative pulpotomy procedures have also been documented where
coronal pulp is removed and the pulp wound is covered by PRF followed
by sealing it with MTA . PRF has also been used to fill in the bony defects
after periapical surgeries like root end resection etc.
Applications of PRF In
Endodontics
30. PRF might serve as a potentially ideal scaffold in revascularization of
immature permanent teeth with necrotic pulps as it is rich in growth
factors, enhances cellular proliferation and differentiation, and acts as a
matrix for tissue ingrowth. The potential theory behind the success of
the use of PRF for regeneration of open apex could be attributed to a
study conducted by Huang et al, who concluded that the PRF causes
proliferation of human Dental Pulp Cells and increases the protein
expression of these Dental Pulp Cells differentiate into odontoblasts like
cells. OPG and ALP expression are generally regarded as markers of
odontoblastic differentiation .
Applications of PRF In
Endodontics
31. 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. Thus PRF is a potential
tool in tissue engineering but clinical aspects of PRF in this field requires further investigation.
Applications of PRF In Tissue
Engineering
32. References
1. Yu-Chao Chang , Kuo-Chin Wu , Jiing-Huei Zhao Clinical application of platelet-rich fibrin
as the sole grafting material in periodontal intrabony defects . Journal of Dental Sciences
(2011) 6, 181e188
2. Preeja Chandran , Arun Sivadas Platelet-rich fibrin: Its role in periodontal
regeneration . The Saudi Journal for Dental Research (2014) 5, 117–122
3. S. GIANNINI , A. CIELO1, L. BONANOME1, C. RASTELLI2, C. DERLA1, F. CORPACI1, G.
FALISI2 . Comparison between PRP, PRGF and PRF: lights and shadows in three similar but
different protocols . European Review for Medical and Pharmacological Sciences 2015; 19:
927-930
4. Sasha Jankovic, Perry Klokkevold, Bozidar Dimitrijevic, Use of Platelet-Rich Fibrin
Membrane
Following Treatment of Gingival Recession: A Randomized Clinical Trial
5. 2.Rock L. Potential of platelet rich fibrin in regenerative periodontal therapy: literature
review. Can J Dent Hygiene. 2013;47(1):33-37.