Role of PLATELET RICH

FIBRIN (PRF) in
Periodontics
Dr. Ibrar Humayun
Department of
Periodontics
LMDC
⦿ PART I
What is PRF????
How PRF has evolved???
Biological characteristics
How the key elements of
PRF function??
⦿ PART II

Preparation technique of
PRF
Optimization of the quality
Handling and application
2
⦿ PART III
Clinical implications of PRF in periodontology
and implantology

3
PART I

4
PRF IS AN AUTOLOGOUS FIBRIN-BASED
(MEMBRANE, MATRIX OR SCAFFOLD) LIVING
BIOMATERIAL, DERIVED FROM HUMAN BLOOD.

ALSO REFERRED TO AS AN OPTIMIZED

BLOOD CLOT

(CHOUKROUN J ET AL 2001, DOHAN ET AL

2006) 5
 PRF

FIBRIN: PLATELETS: LEUKOCYTES STEM CELLS

SUPPORTING RICH IN
MATRIX GROWTH
FACTORS

ANTIBACTERIAL,
NEOVASCULARISATION
AND REGENERATIVE
PROPERTIES

6
MATRIX/ SCAFFOLD BIOLOGICAL
SIGNALS/ GROWTH
PERMITS CELL
FACTORS
MIGRATION INTO
DEFECT AREA ACCELERATES WOUND
HEALING AND
REGENERATION

CELL PROLIFERATION AND DIFFERENTIATION,

EXTRACELLULAR MATRIX SYNTHESIS,
CHEMOTAXIS AND ANGIOGENESIS

TISSUE HEALING AND

REGENERATION

7
THE BLOOD CONCENTRATE WHICH IS OBTAINED
AFTER CENTRIFUGATION HAS 3 DISTINCT LAYERS:

RED BLOOD CELL (RBC) : BASE AT THE

BOTTOM PRF CLOT : MIDDLE

ACELLULAR PLASMA (PLATELET-POOR

PLASMA [PPP]) SUPERNATANT LAYER : TOP

8
THE PRF CLOT IS COMPOSED OF TWO
MAIN PARTS OBSERVABLE WITH THE
NAKED EYE:

A FIBRIN YELLOW PORTION

CONSTITUTING THE MAIN BODY

A RED PORTION LOCATED AT THE END

OF THE CLOT (FULL OF RBCS)

BETWEEN THESE TWO AREAS, A

WHITISH LAYER CALLED THE ‘‘BUFFY
COAT’’

9
 THE FUTURE :
STEM CELL
BLOOD AND BONE
CONCENTRATE REGENERATIVE
ERA ERA
FIBRIN AND
LEUKOCYTE
ERA –
CHOUKROU
GROWTH N’S
FACTOR ERA PRF
– PRP AND
PRGF
FIBRIN
GLUE ERA

10
FIBRIN GLUE ERA:
PLATELET RICH PLASMA (PRP) WAS
FIRST APPLIED AS A “GLUE” IN
SURGICAL PROCEDURES IN THE 1970s

IT IS IDENTICAL TO THE PRESENT-DAY

FIBRIN GLUE EXCEPT THAT IT
PREPARED FROM PLATELET-POOR
PLASMA (PPP)

11
 POSITIVE EFFECT ON TISSUE REPAIR
AND REGENERATION (Currie LJ et al
2001)

USE REMAINS LIMITED OWING TO

THE COMPLEXITY, COST OF
PRODUCTION AND IT IS TIME-
CONSUMING

12
GROWTH FACTOR ERA:

PLATELET-RICH PLASMA (PRP) AND

PLASMA RICH IN GROWTH FACTOR (PRGF)

PRP AS A PROMISING RESERVOIR FOR GROWTH

FACTORS THAT COULD FACILITATE WOUND HEALING
AND
BONE REGENERATION (Marx Reet al 1998;Kassolis JD et
al 2000; Robiony M et al 2002)

PRP HAS TO BE CONVERTED TO A SOLID-FORM PRIOR

TO CLINICAL USE.

13
 THIS CONVERSION WAS ACHIEVED BY
ADDING BOVINE THROMBIN TO PRP
PREPARATIONS TO MINIMIZE THE RAPID
DIFFUSION OF GROWTH FACTORS AT
THE
SURGICAL SITE (Alsousou J et al
2009; Davis VL et al 2014)
DISADVANTAGE:

TECHNIQUE SENSITIVE AND TIME

CONSUMING (REQUIRES AT LEAST
30 MINUTES)

USE OF BOVINE THROMBIN ALSO RAISED

THE CONCERN OF TRANSMISSION OF
UNKNOWN INFECTIONS TO RECIPIENTS.

CONSEQUENTLY, PRP’S
ARE SLOWLY
DISAPPEARING. 14
PLASMA RICH IN GROWTH FACTORS (PRGF)
WAS SUBSEQUENTLY DEVELOPED BY ANITUA AND CO-WORKERS
IN 1999

IT IS CHARACTERIZED BY THE ELIMINATION OF LEUKOCYTES

TO
SUPPRESS THEIR PRO-INFLAMMATORY EFFECT

15
THE FIBRIN AND LEUKOCYTE ERA – CHOUKROUN’S
PRF
IN 2006 CHOUKROUN AND CO-WORKERS DEVELOPED A NOVEL
TECHNIQUE WITH THE AIM OF SIMPLIFYING THE PRP PREPARATION
PROTOCOL AND TO ELIMINATE XENOFACTORS (BOVINE
THROMBIN)

THIS LEAD TO THE SO-CALLED “SECOND GENERATION

PLATELET- DERIVED BIOMATERIALS” DESIGNATED AS PLATELET-
RICH FIBRIN (PRF) OR CHOUKROUN’S PRF

16
 CHOUKROUN’S PRF IS DERIVED FROM THE PATIENTS OWN BLOOD
AND CONTAINS A VARIETY OF BLOOD CELLS INCLUDING :

PLATELETS
B- AND T-LYMPHOCYTES
MONOCYTES
STEM CELLS
NEUTROPHILIC GRANULOCYTES
GROWTH FACTORS

(Kawazoe T et al 2012; Perut F

et al 2013)

17
BLOOD CONCENTRATE ERA:
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)

18
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)

19
BOTH A-PRF AND I-PRF PREPARATIONS ARE
CHARACTERIZED BY PLATELETS, LEUKOCYTES AND
CIRCULATING STEM CELLS, AND ENDOTHELIAL CELLS
CONCENTRATED IN THE
FIBRIN CLOT (Choukroun J 2014)

LEUKOCYTES ARE ENRICHED IN A-PRF AND L-PRF

(Kawase T 2015)

20
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.

21
THE FUTURE - STEM CELL AND
BONE REGENERATIVE ERA:
IT IS HYPOTHESIZED THAT PRF CAN BE A UNIQUE
SOURCE/CARRIER OF HEMATOPOIETIC STEM CELLS (HSCS) WHICH
CAN POTENTIALLY PLAY A MAJOR ROLE IN TISSUE REGENERATIVE
DENTISTRY
(Nicolaidou V et al 2012, HE L et al 2009)

22
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
TUBES.
PLASTIC
T-PRF HAS A HIGHLY ORGANIZED FIBRIN
NETWORK WITH CONTINUOUS INTEGRITY
AS COMPARED TO L-PRF.

23
CLASSIFYING THE MAIN AVAILABLE TECHNIQUES IN 4
FAMILIES DEPENDING ON THEIR LEUKOCYTE CONTENT AND
FIBRIN ARCHITECTURE:

A.Pure Platelet-Rich Plasma (P-PRP) (i.e. Vivostat

PRF, Anitua’s PRGF; PRGF-Endoret or E-PRP) –
Liquid suspension without leukocytes before activation

B.Leukocyte- and Platelet-Rich Plasma (L-PRP) (i.e.

Curasan, Regen, Plateltex, SmartPReP, PCCS,
Magellan) – Liquid suspension with leukocytes before
activation

24
C. Pure Platelet-Rich Fibrin (P-PRF) (i.e. Fibrinet) – Solid
fibrin material without leukocytes.

D. Leukocyte- and Platelet-Rich Fibrin [i.e. Choukrouns

PRF; Advanced PRF, (A-PRF), and injectable i-PRF, (Duo
Process, Nice, France); L-PRF (Intra-Spin, IntraLock,
Boca-Raton, FL, USA); and Concentrated Growth
Factors (CGF) – Solid fibrin material with
leukocytes.

25
The healing and reparation process is totally dependent on the
initial mechanisms of haemostasis. (Clark RA 2001)

PRF technology draws on the following THREE

FUNDAMENTAL PRINCIPLES and biological processes of
haemostasis and wound healing:

PRINCIPLE 1: The presence of a fibrin matrix at the surgical

site acts as a scaffold for recruiting cells (epithelial, fibroblast,
endothelial) throughout the wound healing process.

26
PRINCIPLE 2: Platelets, leukocytes, neutrophils and
monocytes within the fibrin matrix secrete growth
factors and chemotactic proteins that recruit cells to the
surgical site to facilitate wound healing and reparation.

PRINCIPLE 3: Angiogenesis (neovascularization) relies on a

fibrin matrix and stimulation of endothelial cell recruitment
through growth factors (VEGF).

27
28
 The concept of generating a FIBRIN-BASED CELL-SEEDED
MATRIX solely by drawing blood and the slow
polymerization process during centrifugation for 8-12
minutes is truly revolutionary.

PRF can be easily prepared at chair-side within a short

period of time and provides the surgical wound area with a
matrix or scaffold permitting cell migration into the defect
area and with crucial biological signals or growth factors,
potentially accelerating the wound-healing and regeneration
process.

The PRF is therefore an IDEAL SOURCE OF ALL KEY ELEMENTS

involved in the process of tissue healing and regeneration. (Dohan
DM et al 2006, Ghanaati S et al 2007)

29
 FIBRIN MATRIX

The SLOW POLYMERIZATION MODE confers upon the fibrin matrix

its favourable physiologic architecture

The strong 3-dimensional fibrin network functions as an

“ADHESIVE” SCAFFOLDING MATERIAL for endothelial cells
involved in angiogenesis

It functions as an “ADHESIVE”
CARRIER for growth factors and
matrix glycoproteins, and
controls their release and
sustains their bioactivity for ≥ 7
days

30
It is these growth factors that attract endothelial cells into the
fibrin to stimulate formation of new blood vessels (Kobayashi M
2012)

So, the OVERALL QUALITY AND QUANTITY OF FIBRIN FIBERS in

addition to GROWTH FACTORS (GF) may potentially affect the
POTENCY AND EFFICACY of PRF in tissue healing and
regeneration. (Kawase T 2015)

A recent study concluded that AGE could play a significant

role in altering fibrin network patterns thus, influencing the
quality of the PRF clot expected treatment outcomes.
(Yajamanya SR 2016)

31
 PLATELETS

Platelets are merged within the FIBRIN MATRIX in a MESH like a

CEMENT(Dohan Ehrenfest DM 2009) After activation; they start
releasing growth factors.

They support recruitment of cells

from the surrounding host tissue,
and stimulate growth and cell
morphogenesis thus promoting
BONE AND SOFT TISSUE HEALING.

32
Entrapped platelets, releases a broad spectrum of
CYTOKINES, CHEMOKINES, GROWTH FACTORS that facilitate
tissue healing and regeneration.

Upon stimulation, platelets actively participate in pathogen

detection, capturing, and sequestration. (Ghanaati S et al 2014,
Jenne CN 2013)

33
 RELEASE OF GROWTH FACTORS

The PRF membrane stays intact for AT LEAST 7 DAYS and

releases continuously large quantities of growth factors namely:

Transforming growth factor-β 1

[TGFβ1]
Platelet-derived growth factor-
AB [PDGF-AB]
Vascular endothelial growth
factor [VEGF]
Key coagulation and healing
matrix proteins or cytokines
(trombospondin-1, fibronectin,
vitronectin, osteocalcin,
osteonectin)

34
ADVANCED PRF (A-PRF) had a more gradual release of growth
factors up to a 10-DAY period. A-PRF stimulated significantly
HIGHER GROWTH FACTOR RELEASE over time (Kobayashi E
2016)

PLATELETS are not the only blood cells that release growth
factors, but also LEUKOCYTES AND ERYTHROCYTES contain
TGF-β1 and VEGF

The presence of these growth factors are important for

stimulating cell proliferation, matrix remodelling
and angiogenesis during HEALING PROCESS AND
TISSUE REGENERATION

In-vitro studies suggest PRF could potentially effectively promote

BONE REGENERATION. (Wu CL et al 2012)

35
 LEUKOCYTES

Lymphocytes (T and B lymphocytes) enriched PRF (A-PRF and L-PRF)

is reported to be an IDEAL PROVIDER OF LEUKOCYTES.(Ghanaati S et
al 2014)

Primary actions involve antibacterial and osteoconductive actions

(Kawase T. 2015) Most leukocytes are found in the first 25– 30%
proximal part of the clot (Ghanaati S et al 2014)

36
The leukocytes within the dense fibrin network are alive and
function as an IMMUNE NODE that is able to stimulate defence
mechanisms. (Dohan DM 2006)

Leukocytes living in the fibrin matrix are also involved in the

production of significant amounts of growth factors, particularly
TGFβ1 (Dohan Ehrenfest DM 2009)

37
 NEUTROPHILIC GRANULOCYTES

EARLY INFLAMMATORY CELLS due to their phagocytic

capacity, participating in the process of wound debridement
and revascularization.

Neutrophils facilitate trafficking of monocytes into the

wound to phagocytise inflammatory remnants.

A recent study found that changing the

centrifugation protocol in terms of
centrifugation time and speed leads to a
DIFFERENT DISTRIBUTION PATTERN FOR
NEUTROPHILIC GRANULOCYTES. (Ghanaati
S 2014)

38
Accordingly, a HIGHER PRESENCE OF THESE CELLS might be able to
influence the differentiation of host macrophages and
macrophages within the clot after implantation.

So, it is hypothesized that A-PRF might influence BONE AND

SOFT TISSUE REGENERATION, especially through the presence of
monocytes/ macrophages and their growth factors.

39
 MONOCYTES

Monocytes are in essence the ‘VACUUM CLEANERS’ of the body.

They migrate into the wound or inflamed area after the influx of
neutrophils, where they then become MACROPHAGES(Soltan M et al
2012)

The macrophages collect and remove all

the dead, necrotic, bacterial, or foreign
particles in the wound site. This function
is essential for HEALING AND
REGENERATION OF TISSUE, the
production of vascular endothelial
growth factor (VEGF) and
neovascularization.

40
 MESENCHYMAL STEM CELLS (MSC’s)

It is hypothesized that PRF may be a UNIQUE SOURCE OF

HEMATOPOIETIC STEM CELLS (HSCS) that potentially may be of major
importance in bone regenerative procedures. Recently, studies
highlighted the differentiation potential of HSCs. (Nicolaidou V et al
2012, He L wt al 2009)

Ling He and co-workers in

2009 were also able to show
that different cell types, such
as rat osteoblasts, could
DIFFERENTIATE AND
PROLIFERATE WHEN CULTURED
ON THE LEUKOCYTE-RICH PRF
(L-PRF) thus stressing on the
role of MSC’s in PRF

41
The introduction of PRF as a autologous biomaterial has set
in motion an EXCITING AND PROMISING ERA in the advancement
of tissue healing and regeneration

PRF is an AUTOLOGOUS FIBRIN-BASED living biomaterial, derived

from human blood, also referred to as an optimized blood clot.

The key elements are all ACTIVE COMPONENTS OF

PRF. The purpose of PRF technology is to extract from a
patients’ blood sample these key elements and to prepare it
in a CLINICALLY USABLE FORM

42
The concept of generating a cell-seeded fibrin matrix, solely by
drawing the patients’ own blood and centrifugation for 8–12
minutes is TRULY REVOLUTIONARY as it can be made easily at
CHAIR SIDE IN A SHORT PERIOD OF TIME

The use of PRF enables LOCAL DELIVERY of a fibrin matrix,

cells, growth factors and proteins potentially accelerate
WOUND HEALING AND TISSUE REGENERATION and at the
same
time REDUCING MORBIDITY due to its antibacterial and anti-
haemorrhagic effects, with virtually no risk of rejection.

The future of PRF and it applications has ENORMOUS

THERAPEUTIC IMPLICATIONS, but developing and strengthening
its role is dependent on its COHERENCE AND SCIENTIFIC
CLARITY. Independent and robust scientific studies are needed
to STANDARDIZE PRF PROCESS that will enhance therapeutic
outcomes.

43
PART II

44
 BLOOD DRAWING:

Major advantage: It has a

simple preparation
protocol

Blood is drawn from the

patient (2-12 tubes) using a
sterile10ml vacutainer just
before or during surgery.

45
 The tubes with collected
blood samples are
IMMEDIATELY (WITHIN 2
MINUTES after collecting the
blood sample) placed in the
centrifuge and processed
using a single centrifugation
step.

The clinical success of the PRF protocol is dependent on a QUICK

COLLECTION OF BLOOD and its TRANSFER TO THE CENTRIFUGE
because blood will automatically start to coagulate after 1-2
minute and make it difficult to obtain the required
clot quality. (Dohan DM 2006)

Failure to accomplish the quick preparation of PRF could cause

a DIFFUSE POLYMERIZATION OF FIBRIN, which is not ideal for
tissue healing.
46
CENTRIFUGATION:

The tubes should always be

BALANCED by opposing two tubes
to equilibrate the centrifugation
forces and to prevent vibrations.

At the end of the

centrifugation spin, the caps
are removed and the TUBES
PLACED IN A STERILE TUBE
HOLDER.

47
 The blood sample
with clot is allowed
to rest/mature for
approximately 4-8
MINUTES BEFORE
EXTRACTING
the clot from the
tube.

The centrifugation process

activates the coagulation process
and separates the blood sample
into THREE DIFFERENT LAYERS:

48
CENTRIFUGATION PROTOCOLS:

ORIGINAL CHOUKROUN’S PRF PROTOCOL (STANDARD

PROTOCOL): 3000 RPM / 10 MINUTES

DOHAN EHRENFEST’S GROUP - LEUKOCYTE- AND

PLATELET- RICH FIBRIN (L-PRF): 2700 RPM / 12 MINUTES

CHOUKROUN’S ADVANCED PRF (A-PRF) ENRICHED WITH

LEUKOCYTES: 1500 RPM / 14 MINUTES

CHOUKROUN’S I-PRF (SOLUTION/GEL): 700 RPM/8

MINUTES TITANIUM PRF (T-PRF) : 2800 RPM /12 MINUTES

(SAME AS L-
PRF) ONLY TITANIUM TUBE IS USED

49
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
A-
PRF (1300rpm) that produced a LESS DENSE FIBRIN CLOT with a
looser inter-fibrous structure containing more cells. (Ghanaati S
et al 2014)

50
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)

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)

The latter investigators concluded that A-PRF may prove

CLINICALLY BENEFICIAL for future regenerative procedures.

51
Research data suggest that THE TYPE OF VACUTUBE that is used
(i.e. dry glass or glass-coated plastic tubes) and the COMPRESSION
PROCESS OF THE CLOT (forcible or soft) DO NOT seem to influence
the architecture of this autologous biomaterial.

However, both parameters could

influence the growth-factor
content and the matrix
properties of the product.
(Dohan Ehrenfest DM 2010)

52
 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.
53
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 conditions.

54
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)

55
There is NOT A SINGLE RCT OR CCT to compare the
effectiveness of any of the above mentioned PRF (A-PRF or L-
PRF) protocols. Furthermore, in vitro studies that claim
superiority or inferiority of a specific PRF preparation have not
been validated by independent clinical trials.

Therefore, based on these facts, NO PREFERENCE OR DISTINCTION

is made between any of the above-mentioned PRF preparation
protocols (A-PRF or L-PRF).

56
LIMIT CENTRIFUGE VIBRATION DURING PRF PREPARATION

Follow the below rules:

(i)Always make sure that the centrifuge tubes are filled

equally (1cm from the top)

(ii)Always balance the rotor properly. Every tube must have a

balancing or opposing tube

(iii) Do not balance with a vacutube filled with

water, the distribution of the densities will be incorrect and
cause unnecessary vibration

(iv)If properly balanced and used, the rotor should accelerate

smoothly and with a constant change in the pitch of the motor
sound. All rotors go through a minor vibration phase when they
first start.
57
(v) Any vibrations, or unusual sounds should cause the cessation of
operation immediately by the operator

(vi) Initial vibrations with start of centrifugation can be reduced by

holding your hand on the lid

(vii)Never leave the centrifuge until you are certain that it has
reached its operating speed and if the rotor reaches this vibration
point - do not confuse this with a serious vibration caused by
imbalance.

58
PATIENTS RECEIVING ANTICOAGULANTS

When patients are on any type of anticoagulant therapy they have

a longer coagulation time, therefore it is suggested to centrifuge
blood for longer periods, or increase the waiting time after
centrifugation (approximately 5-10 minutes).
However, there is no data available to support this
recommendation.

STANDARDISED AND EFFICIENT PREPARATION OF PRF

The PRF box was designed to collect and transform up to 16 PRF

clots into membranes in sterile conditions and to conserve them
in a clean and wet environment before use.

Compressing the clot too hard or too long results in SHRINKAGE

of the fibrin network, release of growth factors, dehydration and
damage of leukocyte content.

59
PRF membranes or plugs are ready for use within 2 minutes after
compression of clots.

The serum exudate collected in the bottom of the box, can

be used for a longer conservation of the membranes, and can be
mixed with a bone biomaterial for grafting.

This standardized approach also allows an INCREASE IN THE

TOTAL GROWTH FACTOR RELEASE of the PRF membrane
itself. (Dohan Ehrenfest DM 2010)

60
The exudate in the bottom of the box is rich in proteins
(Vitronectin and Fibronectin). This solution can be recovered
with a syringe and used to hydrate biomaterials, flush the
surgical site, wet the implant surface and to preserve
harvested autogenous bone blocks, rather than using saline.

61
CONSERVATION OF PRF MEMBRANE:
PRF must be handled carefully to keep its cellular content alive
and stable. CONSERVE THE PRF CLOT IN ITS CENTRIFUGATION
TUBE. It is a good way to gain 5-15 minutes.

PRF membranes remains usable many hours after

preparation, as long as the PRF is prepared correctly and
conserved in physiologic conditions.

The PRF Box, a user-friendly and inexpensive tool which

optimises the quality of PRF (Dohan Ehrenfest DM 2010)

62
OPTIMAL PREPARATION AND SELECTION:

Platelet-rich region adjacent to the red

thrombus should be used. (Kobayashi M 2012)

Always place the part of the clot close to the

thrombus closest to the grafting site. This
contains the highest concentration of platelets
and stem cells required for bone regeneration.

Thus, it is necessary to preserve a small RBC

layer at the PRF clot end to collect as many
platelets and leukocytes as possible. This part of
the procedure is done with scissors and remains
operator-dependent. (Del Corso M 2009)

63
OPTIMISING AND PRESERVING GROWTH FACTOR RELEASE:

PRF membranes should always be preserved in a wet serum

environment.

The COMPRESSION PROCEDURE of the clots into membranes is

performed with a gentle, slow, and homogeneous pressure to
prevent squeezing out all the serum contained in the original PRF
clot. (Kobayashi M 2012)

This gentle method thus avoids extracting and losing a

significant amount of platelet growth factors.(Dohan DM 2006)

64
 The release of growth factors is considerably less
OL significant when forcible extraction is avoided. In
physiologic conditions, the main release occurs after
D several hours and PRF can be used a long time after
preparation, as long as the material is conserved in the
adequate conditions.(Dohan DM 2006)

Significant amounts of growth factors are

RECEN released during the first 20 minutes after
T preparation. (Dohan Ehrenfest DM 2009) PRF
MEMBRANES SHOULD THEREFORE BE USED
AS QUICKLY AS POSSIBLE AFTER
PREPARATION.

65
HANDLING THE PRF: (CLINICAL APPLICATION)

PRF membranes are EASY TO DRAPE over a surgical or

augmented site. The elastic consistency of the PRF membrane
also allows the clinician to punch a hole in the membrane to
drape over a healing abutment before suturing the flap. (Del
Corso M 2012)

66
Mixing autogenous bone or bone substitutes (allografts) with i-PRF
(PRF Liquid) for use in GBR procedures transforms particulate
bone into a easy to handle gel consistency

67
PRF liquid (i-PRF) can be injected above or PRF (A-PRF or
L-PRF) membrane placed above the GBR or GTR membrane
to act as an interposition barrier to protect and stimulate the
bone compartment and as a healing membrane in order to
improve the soft tissue healing and remodeling and thus avoid
soft tissue dehiscence. (Del Corso M 2013)

68
STAND-ALONE
THERAPIES:

INJECTABLE
CLOT MEMBRANE LIQUID

69
PLUG CUT IN FRAGMENTS

70
ADDITIVE THERAPIES:
Research suggest that bone healing is more effective when PRF IS
MIXED WITH AUTOGENOUS BONE OR BONE SUBSTITUTES in bone
augmentation or GBR procedures. (Ezirganli S 2015)

PRF MIXED WITH AUTOGENOUS BONE OR BONE SUBSTITUTES

71
COMBINATION THERAPIES: The PRF membrane is typically used in
combination with other biomaterials in bone augmentation and
grafting sites as a graft material or barrier membrane.(Soydan SS
2014)

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 weakened gingival tissues and to prevent
associated contamination of the bone graft below.

72
73
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.

74
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.
(Del Corso M 2009)

75
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.

76
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)

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.
(Del Corso M 2009)

77
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)

78
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)

79
 EASY AND EFFICIENT TO USE
Preparing PRF is EASY, FAST AND USER-FRIENDLY
within the daily clinical routine. (Mazor Z et al 2009)

PRF is PREPARED ON SITE simply by DRAWING BLOOD

FROM THE
PATIENT for IMMEDIATE USE thus reducing patient
waiting time.

Currently used protocols for the preparation of autologous

PRF are STANDARDIZED AND EASY TO USE.

In comparison with a natural blood clot, A PRF MEMBRANE IS A

SOLID MATERIAL, HAS A STRONG FIBRIN ARCHITECTURE, AND
EASIER TO HANDLE AND TO POSITION. (Mazor Z et al 2009)

Fibrin 3D architecture provides the PRF membrane with

great density, elasticity, flexibility and strength (Dohan DM 2006) that
is better suited for manipulation and suturing. (Ghanaati S et al 2014)

80
INCREASED CLINICAL PERFORMANCE
PRF exhibits a greater expression and concentration of
growth factors and matrix proteins, which are released more
slowly due to the three-dimensional architecture of the
adhesive glycoproteins in the fibrin, which results in
SIGNIFICANTLY BETTER PERFORMANCE. (Dohan Ehrenfest DM
et al 2009)

Moreover, A-PRF shows 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 et al 2016)

81
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)

82
INCREASED HEALING POTENTIAL
PRF increases the predictability of wound healing and
regeneration potential of tissues. (Hauser F et al 2013)

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)

83
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 post-
operative 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)

84
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.

85
It can spare the patient from ADDITIONAL OPERATING FIELD
(SECOND SURGERY MORBIDITY) and also SAVE COST through avoiding
use of alloplastic or xenogenic membranes and reduce the quantity of
synthetic grafting materials. (Ghetiu A et al 2015)

It is also an ECONOMICAL ALTERNATIVE to expensive recombinant

growth factors when used in conjunction with osseous grafts.

86
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)

87
The RAPID USE OF THE PRF WITHOUT DELAY OR IT’S SHORT
HANDLING TIME may be a potential limitation.

LACK OF RIGIDITY AND FAST DEGRADATION (BIODEGRADABILITY)

(Gruber R et al 2004) (Weibrich G et al 2005) (Simonpieri A et
al 2009) may limit its application in GTR procedures.

PRF can be considered a healing biomaterial that can be utilized in

regenerative surgical procedures to fasten healing, BUT ITS
APPLICATION AS A BARRIER MEMBRANE IN GTR/GBR IS DOUBTFUL
DUE TO ITS POOR MECHANICAL PROPERTIES. (Sam G et al 2015)

88
Owing to the fact that PRF is an autologous product, the
AVAILABILITY OF THIS BIOMATERIAL IN LARGER AMOUNTS
IS ALSO A CONCERN.

One of the clinical limitations to deal with is the

HETEROGENEITY IN THE QUALITY OF PLATELETS AND
BLOOD COMPONENTS.

At present, VERY LITTLE IS UNDERSTOOD about PRF

GENERATED FROM PATIENTS WITH COAGULATION DISORDERS
OR PATIENTS ON MEDICATIONS THAT AFFECT BLOOD CLOTTING
(HEPARIN, WARFARIN OR PLATELET INHIBITORS).

89
The therapeutic use of PRF for accelerating tissue healing and
regeneration has increasingly grabbed the attention of clinicians
world-wide because THIS BIOMATERIAL IS OF NATURAL ORIGIN
(DERIVED FROM THE PATIENTS’ OWN BLOOD)

OPTIMAL PRF MEMBRANE QUALITY is dependent on: QUICK

COLLECTION OF BLOOD AND TRANSFER TO THE CENTRIFUGE;
USE OF PROPER CENTRIFUGATION PROTOCOL; MATURATION
OF THE CLOT FOR 5 MINUTES BEFORE USE; PREPARATION OF
THE MEMBRANE USING A STANDARDIZED PREPARATION
TECHNIQUE; AND APPROPRIATE CONSERVATION OF THE
MEMBRANE BEFORE USE.

90
The PRF can be used as a MEMBRANE (A-PRF OR L-PRF), GEL
(i-PRF), plug or the membrane can be CUT IN FRAGMENTS,
and applied either in STAND-ALONE THERAPIES (I.E. PLUG,
FILLER OR PROTECTIVE BARRIER); ADDITIVE THERAPIES
(I.E. ADDED OR MIXED TO BONE SUBSTITUTES); or used in
COMBINATION THERAPIES WITH OTHER BIOMATERIALS (I.E.
PROTECTIVE BARRIER IN GTR/GBR PROCEDURES).

More importantly, the use of PRF ENABLES LOCAL DELIVERY

OF
A FIBRIN MATRIX, CELLS, GROWTH FACTORS AND PROTEINS
that provide unique biological properties and cues for
promoting new blood vessel formation, and potentially
accelerating wound healing and tissue regeneration, whilst
at the same time reducing adverse events.

91
Consequently, the BENEFITS OF PRF IN WOUND AND BONE
HEALING, its ANTIBACTERIAL AND ANTIHAEMORRAGIC EFFECTS,
the LOW RISKS WITH ITS USE, and the AVAILABILITY OF EASY
AND
LOW COST PREPARATION METHODS should encourage more
clinicians to adopt this technology in there practice for the benefit
there patients.

One of the clinical LIMITATIONS to deal with is the

HETEROGENEITY IN THE QUALITY AND QUANTITY OF PLATELETS
AND BLOOD COMPONENTS due to use of different PRF preparation
protocols.

92
PART III

93
Use prf in surgical situations where :

PROTECTION AND STIMULATION OF HEALING AND

REGENERATION IS CRITICAL

WHEN PROGNOSIS FOR TISSUE REPAIR IS POOR

WHERE POTENTIALLY COMPROMISED IN THE ABSENCE OF

A
TISSUE REGENERATION SCAFFOLD AND

FOR ADDITION OF GROWTH FACTORS.

94
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) 95
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)

96
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)

97
The PRF membrane is recommended as an INEXPENSIVE
AND EASILY HANDLED SUBSTITUTION BIOMATERIAL DURING SINUS
ELEVATION, to reduce the healing time before loading.

Its FIBRIN MATRIX PROPERTIES and ABILITY OF SLOWLY RELEASING

GROWTH FACTORS makes it an IDEAL REPLACEMENT BIOMATERIAL
to
replace xenogenic and expensive collagen membranes in some
situations. (Mazor Z et al 2009)

98
The review also suggests that PRF COMBINED WITH A BONE
ALLOGRAFT OR OTHER BONE SUBSTITUTES accelerates
graft maturation and decreases the healing period before
implant placement. (Ali S et al 2016)

99
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)

100
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)

101
Alternatively, PRF CAN ALSO BE MIXED WITH A BONE SUBSTITUTE
TO FILL THE SOCKET and used as a PROTECTIVE COVER OVER
THE GRAFTED SOCKET.

This is particularly important when GINGIVAL WOUND CLOSURE IS

IMPOSSIBLE OR DIFFICULT WITH THE SUTURES.

The purpose of the PRF membrane is TO STIMULATE GINGIVAL HEALING,

but also to PROTECT THE BONE GRAFT from the oral environment and
to MAINTAIN IT WITHIN THE EXTRACTION SOCKET, LIKE A BIOLOGICAL
BARRIER. It is suggested that this technique negates the need for using
more complex flaps and GBR protocols to close and augment extraction
sockets. (Del Corso M 2012)

102
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)

103
Studies have demonstrated that the use OF LEUKOCYTE-PLATELET
RICH FIBRIN (L-PRF OR A-PRF) MEMBRANES for the STIMULATION
OF BONE AND GINGIVAL HEALING AROUND THE IMPLANT is
particularly
significant. (Boora P et al 2015)

The ELASTIC CONSISTENCY OF THE PRF MEMBRANE allows the

clinician to punch a hole in the membrane to facilitate draping the
membrane over the healing abutment.

104
TREATMENT OF PERI-IMPLANT OSSEOUS DEFECTS:

One clinical study showed that TREATMENT OF PERI-IMPLANT

DEFECTS WITH PRF was clinically more effective than with
CONVENTIONAL FLAP SURGERY ALONE, IRRESPECTIVE OF
THE
TYPE OF DEFECT.(Hamzacebi B et al 2015)

The authors concluded that the use of PRF added to the

maintenance of the graft homeostasis due to release of growth
factors, thus contributing to the successful outcome of
treatment.(Shilbli JA et al 2013)

105
In another study a successful treatment outcome was
also reported after DEBRIDEMENT AND DETOXIFICATION WITH A
CR,CR:YCGG LASER, FOLLOWED BY FILLING THE DEFECT WITH
A
SYNTHETIC HYDROXYAPATITE embedded in native blood and
covered with a PRF membrane TO PREVENT SOFT TISSUE
INFILTRATION INTO THE GRAFTED AREA.

106
AUGMENTATION OF DEHISCENCE AND FENESTRATION DEFECTS:

Case reports indicate that PRF MEMBRANE CUT IN PIECES OR

i-PRF COMBINED WITH BONE SUBSTITUTES may offer an easy
and simple method of handling and delivery of fibrin scaffold,
growth factors and cells during the augmentation of
dehiscence and fenestration defects, and at the same time
reduce soft tissue and bone healing time.(Simonpieri A et al
2009)

PRF has also been successfully used to treat fenestration

defects around implants.(Vijayalakshmi R et al 2012)

107
REMEMBER...............

PRF membrane CUT IN PIECES or PLATELET LIQUID (I-PRF) CAN BE

MIXED WITH BONE GRAFT MATERIAL to cover the defect. The
graft is covered with a resorbable collagen membrane to
maintain form and shape and to confer graft stability and space
maintenance on the bone particles.

108
PRF membrane is then placed on top of the collagen
membrane to PREVENT TISSUE DEHISCENCE AND AID IN
SOFT TISSUE HEALING.

The application of PRF to GBR procedures offers several

advantages including PROMOTING WOUND HEALING, BONE
GROWTH AND MATURATION, GRAFT STABILIZATION,
WOUND SEALING AND HEMOSTASIS AND IMPROVING THE
HANDLING PROPERTIES OF GRAFT MATERIALS.

SOME AUTHORS SUGGEST THAT PRF MEMBRANE IS

NOT EFFECTIVE ALONE. USE OF COLLAGEN
MEMBRANE IS ESSENTIAL ALONG WITH IT. (Toeroek R
et al 2013)

109
AUGMENTATION PROCEDURES:

Several cases have been reported of SUCCESSFUL AUGMENTATION

OF ALVEOLAR RIDGES where there is a buccal bone defect (GBR)
USING PRF COMBINED WITH A BONE SUBSTITUTE (Tatullo M et al
2012) and in cases of the SEVERELY RESORBED POSTERIOR
MANDIBLE.(Del
Corso M 2013)
The authors suggest that THREE LAYERS OF PRF MEMBRANES USED
ALONE were adequate to use as COMPETITIVE INTERPOSITION
BARRIER to PROTECT AND STIMULATE THE BONE COMPARTMENT,
and as HEALING MEMBRANES TO STIMULATE THE PERIOSTEUM AND
GINGIVAL HEALING AND REMODELLING. (Toeroek R et al 2013)

110
The CONCEPT OF USING PRF ALONE AS A GBR BARRIER still
raises many questions as well as limitations and needs to be
investigated with robust RCT’s to determine appropriate
indications and relevant combinations.

111
GUIDED BONE REGENERATION:

A MIXTURE OF BONE GRAFTING MATERIAL WITH I-PRF OR

PRF MEMBRANE OR CLOT CUT IN SMALL PIECES should be
used.

The OBJECTIVE of this mixture is to help the RAPID

VASCULARIZATION OF THE BONE GRAFTING MATERIAL THROUGH
THE PRF FIBRIN MATRIX MAKING THE BRIDGE BETWEEN BONE
PARTICLES and allowing a QUICK NEW BONE GROWTH, while the
XENOGRAFT MATERIAL SERVES AS SPACE MAINTAINER FOR THE
REGENERATIVE VOLUME and SUPPORTS THE NUCLEATION AND
ACCUMULATION OF NEWLY FORMED BONE MATRIX.

112
The bone/PRF mixture in the augmented site is COVERED WITH A
CROSS-LINKED COLLAGEN MEMBRANE TO MAINTAIN THE BONE
COMPARTMENT AND TO PREVENT INGROWTH OF SOFT TISSUE.
The collagen membrane is overlaid with a double layer of PRF
membranes. (Del Corso M et al 2013)

113
INCREASING IMPLANT STABILITY:
Case studies suggest that PRF application into the osteotomy site
INCREASES IMPLANT STABILITY during the early healing period.
Simple application of this material also seems to provide
FASTER OSSEOINTEGRATION.(Öncu E 2013)

114
115
116
Periodontal surgery
Most of the clinical research in periodontology is currently focused
in the fields of improving clinical outcomes with TREATMENT OF
INTRA-BONY PERIODONTAL POCKETS, FURCATION DEFECTS,
GINGIVAL RECESSION DEFECTS, AND HEALING OF CONNECTIVE
TISSUE GRAFT SITES IN THE PALATE.

117
INTRABONY AND FURCATION PERIODONTAL DEFECTS:
The REGENERATIVE AND WOUND HEALING EFFECTS have been
very PROMISING WITH PRF TREATING INTRABONY DEFECTS.

The clinical evidence is supported by several case studies

reporting on the successful application of PRF TO REGENERATE
BONE AND GINGIVAL TISSUES AROUND TEETH PRESENTING
WITH INTRABONY DEFECTS AND FURCATION LESIONS.

Another study has also reported on using PRF SUCCESSFULLY

AS A REGENERATIVE MATERIAL IN CASES OF AGGRESSIVE
PERIODONTITIS. (Desarda HM et al 2011)

Surgical periodontal therapy accompanying the placement

of PRF in angular defects of aggressive periodontitis patients
showed decreased probing pocket depth, increased
attachment level and radiographic bone fill when baseline
and 9 month follow-up data was compared.

118
PLATELET RICH FIBRIN acts as a STABILIZED BLOOD CLOT and
therefore recommended as a PERFECT FILLING MATERIAL for NATURAL
TISSUE REGENERATION AND HEALING.(Del Corso M et al 2012)

Clinically, the general concept of NATURAL TISSUE REGENERATION

(NTR) AND NATURAL BONE REGENERATION (NBR) requires to FILL THE
PERIODONTAL INTRABONY DEFECT WITH PRF MEMBRANE

Most times it is in association with a BONE SUBSTITUTE USED AS A SOLID

SPACE MAINTAINER, and then to COVER THE FILLED INTRABONY
DEFECT used for THE PROTECTION OF THE GRAFTED AREA and as a
HEALING
BOOSTER FOR THE SOFT TISSUES above the defects. (Del Corso M 2012)

119
120
121
122
The OBJECTIVE of this cover is not only to protect the blood clot
and/or the filling material, like in the GTR concept, but also to
promote the induction of a strong and thick periosteum and
gingiva.

The 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 2012)

123
The NTR PROTOCOL is VERY SIMPLE AND GIVES EXCELLENT
RESULTS
in most clinical situations, with no contraindication or risk of
negative effects.

However, in order to get the best results, THE CHOICE AND

THE QUANTITY OF THE ADEQUATE BONE SUBSTITUTE IS YET
TO BE
DETERMINED in various clinical configurations.

Theoretically, PRF CAN BE USED AS A SOLE GRAFTING

MATERIAL OR
IN COMBINATION WITH BONE SUBSTITUTES can be used as a filling
material in intrabony defects, following GTR principles.(Mazor Z et
al 2009)

124
PRF MEMBRANE IS A SOLID MATERIAL WITH THE ADVANTAGE THAT
IT IS EASY TO HANDLE AND TO POSITION IN BONY DEFECTS.

PRF MEMBRANES CAN ALSO BE USED AS A PROTECTION

MEMBRANE AFTER THE FILLING OF THE INTRABONY DEFECT.

125
RECESSION DEFECTS AND GUIDED TISSUE REGENERATION (GTR)
The CLINICAL EVIDENCE IS LESS PROMISING with the treatment
of recession defects. (Moraschini V et al 2015) (Keceli HG et al
2015)

Within the limitations of available clinical trials, the clinical

evidence indicate that PRF DOES NOT IMPROVE ROOT COVERAGE
OR INCREASES THE WIDTH OF KERATINIZED MUCOSA IN
MILLER’S
CLASS I AND II GINGIVAL RECESSIONS compared to other
treatment modalities.

126
127
However, cases have been reported where PRF was successfully used
for TREATING LOCALIZED AND MULTIPLE GINGIVAL RECESSIONS.
(Simonpieri, A et al 2011)
(MIXED OPINION BY AUTHORS)

A case study reported that the USE OF PRF MEMBRANE ALONG

WITH THE VISTA TECHNIQUE allows clinicians to successfully TREAT
MULTIPLE RECESSION DEFECTS WITH OPTIMAL ESTHETIC RESULTS
and EXCELLENT SOFT TISSUE PERIOSTEUM HEALING POTENTIAL.

PRF MEMBRANES stimulate the PERIOSTEUM’S REGENERATIVE

PROPERTIES. However, even if PRF membranes do not block the
migration of the cells, no invagination of the soft tissues within
the bone area were observed when PRF membranes covered a
filled intrabony defect. (Simonpieri, A et al 2011)

128
PALATAL BANDAGE
PRF membranes can also be used as a PALATAL WOUND
BANDAGE OR PROTECTION MEMBRANES AFTER HARVESTING
CONNECTIVE TISSUE GRAFTS IN THE PALATE.

Case studies show that PRF membrane used as a palatal bandage is

an efficacious approach TO PROTECT THE RAW WOUND AREA of a
palatal donor site and significantly ACCELERATES PALATAL WOUND
HEALING and REDUCES PATIENT DISCOMFORT AND HEALING TIME.
(Femminella B et al 2015) (Jain V et 2012) (Aravindaksha SP et
al
2014)

129
INTER-DENTAL PAPILLA AUGMENTATION
A case study reported that PRF COMBINED WITH BONE
GRAFT FOR REGENERATION OF INTERDENTAL BONE may
contribute towards IMPROVED CLINICAL SUCCESS WITH
AUGMENTATION
OF LOST DENTAL PAPILLA. The reconstructed papilla in the
new position was stable when reviewed at 3 and 6 months
postoperatively. (Arunachalam LT 2012)

130
PRF is increasingly being investigated and used by clinician’s worldwide
as an ADJUNCTIVE AUTOLOGOUS BIOMATERIAL to PROMOTE BONE
AND SOFT TISSUE HEALING AND REGENERATION.

PRF has also grabbed the attention of clinicians because this

biomaterial is DERIVED FROM THE PATIENTS’ OWN BLOOD; is EASY
TO MAKE AT CHAIR-SIDE, EASY TO USE WITHIN THE DAILY
CLINICAL
ROUTINE; widely applicable in dentistry with virtually NO RISK OF
REJECTION; whilst being FINANCIALLY REALISTIC for the patient and
the practice.

The 3D ARCHITECTURE OF THE FIBRIN MATRIX provides the

PRF membrane with GREAT DENSITY, ELASTICITY, FLEXIBILITY
AND
STRENGTH that are excellently SUITED FOR HANDLING,
MANIPULATION AND SUTURING.

131
The GOLD STANDARD FOR IN VIVO TISSUE HEALING AND
REGENERATION
requires the mutual interaction between a scaffold (fibrin matrix),
platelets, growth factors, leukocytes, and stem cells. THESE KEY
ELEMENTS ARE ALL ACTIVE COMPONENTS OF PRF in whichever form,
and WHEN COMBINED AND PREPARED PROPERLY ARE INVOLVED IN THE
KEY PROCESSES OF TISSUE HEALING AND REGENERATION, whilst at
the
same time reducing adverse events.

Clinicians are using PRF IS EXTENSIVELY AND SUCCESSFULLY USED IN

VARIOUS CLINICAL APPLICATIONS TO PROMOTE WOUND HEALING
AND TISSUE REGENERATION.

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One of the clinical LIMITATIONS to note is the HETEROGENEITY IN THE
QUALITY OF PLATELETS AND BLOOD COMPONENTS due to use of
different PRF preparation protocols in the various studies reviewed.

IRRESPECTIVE OF THE PROTOCOL USED all studies have all reported

SUCCESSFUL OUTCOMES WITH REGARDS TO SOFT AND BONE
TISSUE HEALING AND REGENERATION.

It should also be noted that AT THIS STAGE IN TIME THERE IS NOT A

SINGLE RCT OR CCT TO COMPARE THE EFFECTIVENESS OF A-PRF OR
L- PRF PROTOCOLS.

Furthermore, IN VITRO STUDIES THAT CLAIM SUPERIORITY OR

INFERIORITY OF A SPECIFIC PRF PREPARATION HAVE YET TO
BE VALIDATED BY INDEPENDENT CLINICAL TRIALS.

The FUTURE OF PRF AND ITS APPLICATIONS in clinical dentistry,

especially in the FIELD OF SOFT TISSUE AND BONE REGENERATION has
ENORMOUS IMPLICATIONS, but DEVELOPING AND STRENGTHENING ITS
ROLE IN DENTISTRY IS DEPENDENT ON ITS COHERENCE AND
SCIENTIFIC CLARITY.
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The CLINICAL EFFECTIVENESS OF DIFFERENT PRF PREPARATION
PROTOCOLS in various clinical settings REMAINS TO BE
VALIDATED WITH A GREATER NUMBER OF INDEPENDENT AND
ROBUST RCT’S, PREFERABLY WITH A SPLIT MOUTH DESIGN, AND
LARGER SAMPLE SIZES.

INDEPENDENT, COHERENT AND SCIENTIFIC VALIDATION OF PRF is

needed to ENHANCE THE POTENTIAL OF THIS TECHNOLOGY,
thereby
extending its therapeutic applications.

PRF TECHNOLOGY IS IN ITS INFANCY and will IN FUTURE HAVE A BIG

IMPACT IN DENTISTRY. The benefits derived from the using PRF in
various clinical applications FOR PROMOTING WOUND HEALING AND
TISSUE REGENERATION, ITS ANTIBACTERIAL AND ANTI-
HAEMORRHAGIC EFFECTS, THE LOW RISKS WITH ITS USE, AND THE
AVAILABILITY OF EASY AND LOW COST PREPARATION METHODS,
should encourage more clinicians to adopt this technology in their
practice for the benefit their patients.

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