Platelet Rich Fibrin (PRF) is a platelet concentrate containing growth factors that promotes wound healing. It is prepared from centrifuging the patient's own blood without anticoagulants. PRF forms a fibrin clot that traps platelets, cytokines and cells to slowly release growth factors. It can be used as a membrane or graft material to enhance tissue regeneration due to its angiogenic and immunomodulatory properties. PRF preparation is simple, inexpensive, and avoids risks associated with other graft materials or membranes.
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Introduction to Platelet Rich Fibrin (PRF) and its uses in Dentistry
1. Introduction to Platelet Rich Fibrin (PRF)
and its uses in Dentistry
Dr. Hamza Jawed
Resident OMFS
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 rationale on the fact that platelets play a
crucial role in tissue healing and inflammation.
3. 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
4. Cytokines are also released from the platelets, being
responsible in
1. modulating platelet activation and the
2. proliferation and differentiation of leukocytes,
3. playing an important role in immunology,
specifically, in inflammation mechanism.
5. What are the differences
between
PRP,
PRGF and
PRF ?
6. 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
1. promote tissue repair and
2. affect the behavior of other cells
by modulating the inflammation and the formation of
new blood vessels.
7. Platelet Rich Plasma (PRP):
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
1. bovine thrombin or
2. 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
8. 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.
9. Platelet Rich in Growth Factors (PRGF)
is a type of plasma enriched of proteins and circulating growth
factors able to aid the
1. bone and
2. 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.
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.
10.
11. PRGF preparation was carried out by
following a previously described
protocol.
Blood sample was obtained from
basilic vein using a large needle to
avoid platelet rupture.
12. 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
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.
13. 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.
15. 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
16. Platelet rich fibrin (PRF) is a fibrin matrix in which
1. Platelet cytokines,
2. Growth factors and
3. Cells
are trapped and may be released after a certain time and
that can serve as a resorbable membrane.
It is 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.
17. 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.
It is an autogenous osteo-inductive 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.
18.
19. The various cytokines [8] that are involved in PRF are:
• Transforming growth factor-β
• Platelet-derived growth factor
• Vascular endothelial growth factor
• Insulin growth factor-1
• Fibroblast growth factor
• Epidermal growth factor.
20.
21. Though the classical method for preparation of PRF
was given by Dr. Choukroun, the present technique
for PRF preparation is legitimized by the French
Health Ministry.
Currently, PRF is prepared without any use of
anticoagulant or
bovine thrombin.
22. A PRF with standard quality and quantity of the
fibrin matrix,
leukocytes,
platelets, and
growth factors
demands a standard protocol for preparation
23. The armamentarium for preparation
of PRF includes a
PC-02 table centrifuge and a blood
collection kit that contains in it a
1. 24G butterfly needle and
2. 9-ml blood collection tubes.
The collected patient's blood sample
in 10-ml tubes that is devoid of any
anticoagulant is centrifuged
immediately at a rate of 3000 rpm for
10 min
24.
25.
26.
27.
28.
29.
30. 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
31. 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
32.
33.
34.
35. Current data show that there is a DIFFERENTIAL
DISTRIBUTION of red blood cells, platelets, and
leukocytes in the PRF clot depending
on the CENTRIFUGAL FORCE used. (Ghanaati S et al
2014)
In vitro studies showed that a LONGER
CENTRIFUGATION
PROTOCOL (2700rpm) produces a DENSER
(STRONGER) FIBRIN
CLOT with less inter-fibrous space containing less cells
compared to the SHORTER CENTRIFUGATION
PROTOCOL OF APRF (1300rpm) that produced a LESS
DENSE FIBRIN CLOT with a
looser inter-fibrous structure containing more cells.
(Ghanaati S
et al 2014)
36.
37.
38. Dohan ehrenfest and coworkers found in their in vitro
studies that the
original L-PRF protocol produces
larger clots and membranes, and a
more intense release of growth factors
than the modified A-PRF protocol. (dohan ehrenfest
dm 2014)
39. In-vivo study showed that choukroun’s new formulation
of PRF (A-PRF) had
a more gradual release of growth factors, up to a 10-
day period, and
stimulated significantly higher growth factor release
over time when compared to choukroun’s standard
prf. (kobayashi e 2016
40. The latter investigators concluded that A-PRF may
prove
CLINICALLY BENEFICIAL for future regenerative
procedures.
41.
42. How to prepare a PRF Membrane?
Each fibrin clot concentrates
most platelets (97%) and more
than half of the leukocytes from
a 10-ml blood harvest (dohan
ehrenfest dm)
STEP 1: the prf clot is removed
from the tube with a sterile
tweezer.
STEP 2 : the fibrin clot is
separated from the red blood cell
fragment, approximately 2mm
below the dividing line, using a
scissor.
The section of the blood clot
attached to the fibrin clot contains
the stem cells
43. The PRF clots are placed in
the PRF BOX and covered
with the lid.
The PRF membranes are
ready for use after 2
minutes
A PRF membrane remains
USABLE MANY HOURS
after preparation, as long as
the PRF is prepared
correctly and conserved in
physiologic condition
44. The use of the prf box is a
user-friendly and inexpensive
tool, allows for standardized
preparation of homogeneous
PRF membranes with a higher
growth factor content, avoids
the dehydration of the
leukocytes living in the PRF
clot, and also prevents the
shrinkage of the fibrin matrix
architecture (dohan ehrenfest
dm 2006)
47. The purpose of PRF is to
activate and
facilitate the healing and
regenerative capacity of the host tissue,
by providing a strong fibrin scaffold, major growth
factors and
Allowing space for tissue regeneration.
Using PRF as a protective barriers on bone graft
sites helps to avoid perforations of the damaged
gingival tissues and to prevent associated
contamination of the bone graft below.
48. PRF membranes are not comparable to
heterologous resorbable collagen or non-resorbable
membranes. PRF membranes belong to a
completely different category of membrane, namely
natural autologous membrane. (gassling v et al
2010)
A PRF membrane is as natural as the host tissue,
while heterologous membranes are considered as
foreign bodies by the host tissues and interfere with
the natural tissue healing process.
49. A PRF MEMBRANE CAN BE USED FOR
THREE PURPOSES
BIOACTIVE BARRIER
A PRF membrane is a blood clot prepared in an
optimized form that is rich in cells and growth factors, and
acts as a NATURAL BIOACTIVE BARRIER, allowing
interaction with the tissues below and above it.
This interaction with tissues facilitates NATURAL TISSUE
REGENERATION (NTR) and healing. (Del Corso M
2009)
PRF will undergo a quicker remodeling (biodegradation)
in situ than a resorbable collagen membrane, but will also
promote a strong induction on the periosteum/gingival
tissue due to the slow release of growth factors and other
matrix proteins
50. COMPETITIVE INTERPOSITION BARRIER
GTR MEMBRANES are CELL-PROOF BARRIERS
against soft tissue invagination, whereas PRF
MEMBRANES allow cells to migrate through it, thus
allowing new blood vessel formation that will
facilitate regenerative and healing interactions
between the tissues BELOW AND ABOVE the PRF
membrane
51. The PRF matrix becomes the interface between the
tissues and therefore avoids the migration of the soft
tissues deeper within grafted defect or augmented
site. This biological characteristic is referred to as a
COMPETITIVE BARRIER. (Del Corso M 2009)
52. However, it is important to recognize that using PRF
as a competitive barrier does not have the graft
stability or space maintenance characteristics of
a normal collagen membrane, and therefore
CANNOT BE RECOMMENDED TO USE as such.
53. PROTECTIVE BARRIER AND HEALING BOOSTER
PRF membranes are frequently used for the
protection of the grafted area and as a healing
booster for the soft tissues above the grafted defects
or augmented sites (promote the induction of a
strong and thick periosteum and gingiva) (Del Corso
M 2009)
This boosted periosteum functions as a TRUE
BARRIER between the soft tissue and bone
compartments, and constitutes probably the BEST
PROTECTION AND REGENERATIVE BARRIER for
the intrabony defects. (Del Corso M 2009)
54. BENEFITS of PRF
Natural (autologous) biomaterial while other
membranes are considered as foreign bodies by the
host tissues and interfere with the natural tissue
healing process, a prf membrane is as natural as the
host tissue with virtually no risk of infection, immune
or a rejection reaction (foreign body response).
(dohan dm et al 2006)
55. EASY AND EFFICIENT TO USE
Preparing PRF is EASY, FAST AND USER-
FRIENDLY within the daily clinical routine. (Mazor Z
et al 2009)
56. SAFETY AND LOW RISK
Blood is drawn from the patient and therefore
reduced donor site morbidity.
PRF rarely causes complications such as membrane
exposure, an unwanted outcome that has been
observed in cases using biodegradable barrier
membranes. (Hitti RA 2011)
A further advantage of PRF is the extremely low risk
of infection. Moreover, no in vitro cytotoxicity effects
were detected whatever the quantity of PRF
used.(Dohan Ehrenfest DM 2009)
57. INCREASED HEALING POTENTIAL
PRF increases the predictability of wound healing
and regeneration potential of tissues. (Hauser F et al
2013)
58. REDUCED MORBIDITY
A clinical advantage of PRF as a graft material is
related to avoidance of a donor site and risk of
morbidity, thus resulting in a decrease in patient
discomfort, post-surgical pain and bleeding after
operation. (Del Corso M 2012)
PRF is not only a platelet concentrate but also an
‘IMMUNE NODE’ that is able to stimulate defence
mechanisms. (Dohan DM et al 2006)
59. Furthermore, evidence suggest that the content of
platelet alpha granules might have a bactericidal
effect, mediated by molecules called
THROMBOCIDINES that may have an important
contribution toward reducing postoperative
infections. (Rozman P 2007)
The antihemorrhagic properties (helps in the clotting
of blood and prevents hemorrhage) of PRF are also
advantageous and convenient during surgical
procedures. (Del Corso M 2012)
60. COST-BENEFIT
PRF has a potential outstanding cost to benefit
RATIO. A platelet-rich fibrin (PRF) membrane is a
readily available and inexpensive biomaterial. the
ease of preparation and cost-effectiveness of
PRF membrane offers a huge advantage over other
commercially available membranes. (Choukroun J
2006) PRF is currently the safest and most
economical choice for patients and clinicians for
improving healing and regeneration outcomes
61. NO CONTRAINDICATIONS
PRF has no contraindications, they can be used in
all kinds of patients, especially in patients with
systemic conditions where healing is
compromised (i.e. diabetics and smokers) or in
surgically compromised situations (damaged
flap). In these situations PRF will promote soft tissue
healing and stimulate the healing of a damaged flap
and reduce the risks of flap necrosis after a surgery.
All fibrin-based products (platelet concentrates), are
frequently used for the stimulation of angiogenesis
and to reduce the risk of flap necrosis in many
general surgery applications. (Clark RA 2001) (Van
Hinsbergh, V.W et al 2001)
62. IMPLNTOLOGY and PRF
PRF technology is currently focused in the fields of
improving clinical outcomes with:
SINUS FLOOR ELEVATIONS USING PRF AS SOLE
GRAFTING MATERIAL (Ali S et al 2016)
SINUS FLOOR ELEVATION USING A COMBINATION
OF PRF AND BONE GRAFT (Choukroun J et al 2006)
ALVEOLAR RIDGE PRESERVATION (SOCKET
AUGMENTATION) (Hauser F et al 2013)
PERI-IMPLANT TISSUE HEALING (Boora P et al 2015)
IMPROVING IMPLANT STABILITY (Öncu E 2015)
63. In-vitro studies have shown prf-induces gene
expression of the early and late markers of
osteogenesis thus stimulates bone and soft tissue
healing. (Clipet F et al 2012)
64. SINUS FLOOR ELEVATION USING PRF AS A SOLE
OR COMBINATION WITH BONE GRAFTS:
A systematic review showed that PRF used as a sole
filling material in sinus floor elevation with simultaneous
implant placement is a simple technique with promising
results.
(kanayama t et al 2016) various clinical case reports
describe the lateral approach for sinus floor elevation
using only PRF as the grafting material. (mazor z et al
2009) (simonpieri a et al 2011)
65.
66. Case studies have demonstrated that PRF
membranes can be used successfully as a protective
barrier to cover the sinus membrane during grafting
procedures. (tatullo m et al 2012) (mazor z et al
2009) PRF membranes also represent an easy and
successful method to cover sinus membrane or
osteotomy window to protect the SCHNEIDERIAN
MEMBRANE, facilitate wound closure and to
enhance healing. (tatullo m et al 2012) cases have
also been reported showing that a-prf membrane
can be used as a healing barrier when perforations
or tears of the schneiderian membrane occur. (diss a
et al 2008) (toffler m et al 2010)
67.
68. ALVEOLAR RIDGE PRESERVATION:
use of prf membranes to fill the socket after tooth
extraction has shown to improve alveolar bone healing
and preservation of the alveolar crest width (hauser f et al
2013)
PRF PLUGS OR MEMBRANES can also be used with
compromised extraction sockets (peck mt et al 2011)
severe cystic destructions or after cyst enucleations
(choukroun j et al 2006)
to allow early bone and gingival regeneration required for
implant placement.
Clinical and histological findings suggest that filling a fresh
extraction socket with PRF provides a viable therapeutic
alternative for implant site preparation. (zhao jh et al 2011)
69. IMMEDIATE POSTEXTRACTION IMPLANT
PLACEMENT:
PRF can be considered as a healing biomaterial with
potential beneficial effect on peri-implant tissue and can
be used as a therapeutic adjuvant with immediate implant
placement in the clinical scenario of one stage, single
tooth implant placement procedure in maxillary anterior
region.
(boora p et al 2015) with immediate implant placement
the peri-implant jump gap can be augmented with
PRF CLOT (A-PRF OR L-PRF) OR SOLUTION (I-PRF)
mixed with a bone substitute.(rao sg et al 2013
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