ROLE OF PLATELET RICH FIBRIN

IN PROSTHODONTICS
GUIDE: Dr.K.MURUGESAN MDS Dr.B.MUTHUKUMAR MDS
PROFESSOR PROFESSOR & HOD
CO-GUIDE: Dr.S.SUGANYA MDS
READER
PRESENTED BY
AKSHAYAA B
Ist YEAR PG
 INTRODUCTION
• Regenerative medicine holds promise for the restoration of
tissues and organs damaged by disease, trauma, cancer, or
congenital deformity.
• Regenerative medicine can perhaps be best defined as the
use of a combination of cells, engineering materials, and
suitable biochemical factors to improve or replace
biological functions in an
effort to effect the
advancement of medicine.
 PLATELETS
• Platelets, also known as thrombocytes, are
blood cells responsible for blood clotting. If a
blood vessel wall becomes damaged, platelets
will rush to the site of injury and form a plug
or clot to stop the bleeding.
• Low range: Less than 150,000 platelets per
microliter
• Normal range: 150,000 to 450,000 platelets
per microliter
• Elevated range: 500,000 to 1,000,000
platelets per microliter
• If platelet count is low (a condition
called thrombocytopenia), the risk of
uncontrolled or prolonged bleeding increases.
• When there are too many platelets in the
blood (a condition called thrombocytosis), it
may lead to abnormal blood clot formation,
which can be serious and life-threatening.
 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.
 HISTORY
• Choukroun and his associates were amongst
the pioneers for using PRF protocol in oral an
maxillofacial surgery to improve bone healing
in implant dentistry.
• Gassling et al have shown that PRF is a
suitable scaffold for breeding human
periosteal cells in vitro, which may be suitable
for bone tissue engineering applications
 WOUND HEALING
• Wound healing is a central concept in
regenerative surgical sciences.
• Wound healing occurs as a result of complex
interplay between various cells and signaling
molecules.
• The participating cells include epithelial cells,
osteoblasts, fibroblasts and the signals are those
released from the platelets from the blood clot
including various cytokines and growth factors.
Gupta V, Bains VK, Singh GP, Mathur A, Bains R. Regenerative potential of platelet rich fibrin in dentistry: Literature review. Asian J Oral Health
Allied Sci. 2011 Jan 1;1:23-8.
Platelet-rich plasma (PRP) in dental and oral
surgery: from the wound healing to bone
regeneration
 • In the field of dentistry and oral & maxillofacial
surgery, platelet concentrates have been applied since
more than half a century.
• With the increase in our understanding of the
biological properties of these concentrates, the initial
protocols have undergone immense change.
• The currently used platelet concentrates are not only
much more efficient than their predecessors in the
terms of biological efficacy, but are also much less
complicated, simple and effective.

Tozum TF, Demiralp B. Platelet-rich plasma: a promising innovation in dentistry. Journal-Canadian Dental Association. 2003 Nov;69(10):664-5.
 • In the past decade, second generation platelet
concentrates have gained immense popularity as
bioactive surgical additives in the field of regenerative
dentistry.
• Among the various platelet concentrates, currently, the
most widely used concentrate in dentistry is platelet
rich fibrin (PRF).
• The concept of platelet rich fibrin ushered in an era of
completely autologous form of platelet concentrates
with no addition of bovine thrombin or anticoagulants.

Tozum TF, Demiralp B. Platelet-rich plasma: a promising innovation in dentistry. Journal-Canadian Dental Association. 2003 Nov;69(10):664-5.
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 PREPARATION PROTOCOLS
PRF Described by RPM Time (minutes) Tube
(year)
Leukocyte and Choukroun 2700 12 Glass coated
Platelet rich 2004 tube
fibrin (L-PRF)
Advanced Ghanaati 2014 1300 14 Patented
platelet rich
fibrin (A-PRF)
Advanced Fujioka- 1300 8 Same as A-PRF
platelet rich Kobayashi,
fibrin + Miron 2016
(APRF+)
Injectable Mourão 2015 700 3 Non coated
platelet rich
fibrin (I-PRF)

Maniyar N, Sarode GS, Sarode SC, Shah J. Platelet-Rich fibrin: A “wonder material” in advanced surgical dentistry. Medical Journal of Dr. DY Patil
Vidyapeeth. 2018 Jul 1;11(4):287.
 ADVANTAGES
1.Simplified preparation and efficient technique
2. Accelerates the healing rate of the grafted bone
3. It is available through autologous blood sample
4. Minimal blood manipulation
5. It can be used solely or in combination with other grafts
6. The natural fibrin framework with growth factors within imparts prolonged
activity that stimulates tissue regeneration effectively
7. It circumvents the addition of external thrombin as polymerization is a
completely natural process, thus refraining from any risk of immunological
reaction
8. When used along with bony grafts, it is a quick as well as an economical
alternative when compared with recombinant growth factors

Maniyar N, Sarode GS, Sarode SC, Shah J. Platelet-Rich fibrin: A “wonder material” in advanced surgical dentistry. Medical Journal of Dr. DY Patil
Vidyapeeth. 2018 Jul 1;11(4):287.
 DISADVANTAGES
1. Being autologous in nature, the final amount available is very
less
2. The blood collection time and its transference for the
centrifuge greatly affects the success of PRF
3. Clot polymerization requires the need of using glass‑coated
tube
4. It becomes very difficult to store PRF after preparation and it
shrinks
5. Dehydration causing shrinkage and alteration in structural
integrity of PRF demands its immediate use after preparation
6. Manipulation of PRF requires clinical experience.
Maniyar N, Sarode GS, Sarode SC, Shah J. Platelet-Rich fibrin: A “wonder material” in advanced surgical dentistry. Medical Journal of Dr. DY Patil
Vidyapeeth. 2018 Jul 1;11(4):287.
 EFFECT
BIOLOGIC ACTIONS
MEDIATED BY ACTION
Angiogenesis Vascular endothelial • Cells in the wound vicinity to migrate, divide and
growth factor (VEGF), change phenotype
angiopoetin, • stimulates expression of α5β3 intergrin on the
platelet derived growth endothelial cells which promotes the binding of
factor endothelial cells to fibrin, fibronectin & vitronectin.
(PDGF), basic fibroblast
growth factor (FGF-b).

Mitogenesis TGF-β • Mitogen for cells including fibroblasts, marrow

Fine & flexible stem cells, endothelial
trimolecular/ cells, pre-osteoblasts, mesenchymal cells
equilateral junctions • Inhibitory effect on osteoclasts
• Enhanced cytokine entrapment, promotes rapid
cellular migration
Immunomodu Fibrin and its •Stimulate migration, phagocytosis and enzymatic
latory degradation products degradation by neutrophils
effects Fibronectin •Releases certain chemotactic factors which regulate
Leukocytes wound colonization
IL-4 by macrophages
• Increased degranulation to release several
molecules including
IL-1, IL-4, IL-6 and TNF-α
Wound Fibrinogen, fibronectin, • Undergoes degradation and allows
recolonization vitronectin and tenascin epithelial cell migration on
Fibrin wound margins
• Binds to several molecules including
fibronectin, PDGF & TGF-b
through the αVβ3 integrin
• Promotes the migration of fibroblasts
Osteogenic effect • May upregulate the expression of alkaline
phosphatase and osteoprotegerin
• Enhance the expression of phosphorylated
extracellular signalregulated
protein kinase, osteoprotegerin and alkaline
phosphatase
activity
Entrapment of Even though the intrinsic content of stem
stem cells cells in quite low, it has been hypothesized
that the fibrin clot may act like a trap for
circulating stem cells which may converge to
a secretory phenotype allowing vascular and
tissue restoration.

Shah R, Thomas R, Mehta DS. An Update on the Protocols and Biologic Actions of Platelet Rich Fibrin in Dentistry. The European journal of
prosthodontics and restorative dentistry. 2017 Jun;25(2):64-72.
 INJECTABLE PRF
• One of the latest developments in the PRF technology is the
production of injectable PRF (i-PRF).
• It has been used for mixing with bone grafts, which on
completion of the coagulation process forms a gel-putty
consistency with the graft particles incorporated in the graft.
• The graft thus formed has a good workable
consistency, leads to decreased leaching of the graft as
it is tightly encapsulated in the fibrin matrix .
• Mixing the bone graft with i-PRF also gives the benefit
of growth factor release at the recipient site which
would otherwise be missing in a normal bone graft.
• This has the potential to convert any osteoconductive
graft to osteopromotive (due to the presence of
platelets & growth factors) which would translate into
faster and better efficiency of bone formation.
 PRF LYSATE
• A newer application of PRF based products is the PRF Lysate.
In this, after PRF preparation, it is incubated at 37°C in a
humidified atmosphere of 5% CO2/95% air and the exudate
thus collected has been referred to as PRF lysate.
• It is said to be a good source of several growth factors
including PDGF, TGF,VEGF & EGF.
 Titanium PRF
• T-PRF samples seemed to have a highly organized
network with continuous integrity compared to the
L-PRF samples.
• When the same was applied for palatal mucosal
wound healing, it was found that T-PRF membranes
exhibited positive effects on palatal
mucosal wound healing.
CLINICAL CONSIDERATIONS
• In dentistry, PRF is being widely accepted and
used for varied applications. It has been used
as a sole material with good success rate for
sinus lift & socket preservation.
 • Used for all grafting applications including guided
tissue regeneration in intra-bony defects and Grade II
furcation involvements, guided bone regeneration in
cases of socket preservation/ augmentation, for
combined endodontic-periodontal lesions, hard and
soft tissue augmentation around implants, to be
mixed with bone grafts to increase their volume &
bioactivity

Huang FM, Yang SF, Zhao JH, Chang YC. Platelet-rich fibrin increases proliferation and differentiation of human dental pulp cells. Journal of
endodontics. 2010 Oct 1;36(10):1628-32.
• It has also been used as a scaffold to culture
human periosteal cells for tissue engineering
purposes.
 • PRF is a healing biomaterial with a great
potential for bone and soft tissue
regeneration, without inflammatory reactions
and may be used alone or in combination with
bone grafts, promoting hemostasis, bone
growth, and maturation.

Borie E, Oliví DG, Orsi IA, Garlet K, Weber B, Beltrán V, Fuentes R. Platelet-rich fibrin application in dentistry: a literature review. International
journal of clinical and experimental medicine. 2015;8(5):7922.
• PRF has immunological and antibacterial
properties, may lead to leukocyte
degranulation, and has some cytokines that
may induce angiogenesis and pro/anti-
inflammatory reactions.
 • PRF could serve as a resorbable membrane for
guided bone regeneration (GBR) [22],
preventing the migration of non-desirable
cells into bone defect and providing a space
that allows the immigration of osteogenic and
angiogenic cells and permits the underlying
blood clot to mineralize

Verma A, Srivastava S, Khurshid S, Parveen F, Pandey P. Platelet rich fibrin: a promising innovation in regenerative therapy. Journal of Evolution of
 OTHER CLINICAL IMPLICATIONS
• To enhance healing of the donor site post
harvesting of free gingival graft
• For pulp revascularization and dentinogenesis
of a necrotic tooth
• To preserve height of the alveolar ridge after
extraction of multiple teeth
• After transalveolar extraction procedure
• As an adjuvant to healing of orofacial fractures
• For peri‑implant bone regeneration
• Bone reconstruction of large surgical defects after
oral cancer therapy
• To fill the defects created after removal of cystic
pathologies
• As an additive to promote healing after ablative
surgical treatment of oral mucosal lesions
• For tissue volumerization
• Autologous fat transfer procedures
• For the treatment of articular cartilaginous
defects of temporomandibular joint
• Mineralized PRF can be used for bone
replacement procedures
• In localized osteitis.
PLATELET RICH PLASMA
• PRP is a new application of tissue engineering and a
developing area for clinicians and researchers.
• It is a storage vehicle for growth factors, especially
PDGF and TGF-b, both of which influence bone
regeneration.
• Reduction of bleeding and rapid healing hold promise
for further procedures.
• Most important, this autologous product eliminates
concerns about immunogenic reactions and disease
transmission.
Arora NS, Ramanayake T, Ren YF, Romanos GE. Platelet-rich plasma: a literature review. Implant dentistry. 2009 Aug 1;18(4):303-10.
 MECHANISM OF ACTION
• PRP works via the degranulation of the
granules in platelets, which contain the
synthesized and prepackaged growth factors.
• The active secretion of these growth factors is
initiated by the clotting process of blood and
begins within 10 minutes after clotting.
• More than 95% of the presynthesized growth
factors are secreted within 1 hour. Therefore

Kang YH, Jeon SH, Park JY, Chung JH, Choung YH, Choung HW, Kim ES, Choung PH. Platelet-rich fibrin is a Bioscaffold and reservoir of growth
factors for tissue regeneration. Tissue Engineering Part A. 2011 Feb 1;17(3-4):349-59.
 • PRP enhances the early wound-healing cascade
by the interactions of activated platelet-released
growth factors with the extra cellular matrix
with potential potent anabolic affects.
• Platelets in PRP also play a role in host defence
mechanism at the wound site b producing
signalling proteins that attract macrophages.

Kaur P, Puneet VD, Dahiya V. Platelet-rich plasma: A novel bioengineering concept. Trends Biomater Artif Organs. 2011 Apr 1;25(2):86-90.
PLATELET RICH PLASMA
VS
PLATELET RICH FIBRIN
 First generation ‑ PRP
Based on •Use of bovine thrombin and calcium
processing chloride (anticoagulants)
technique •Two spin centrifugation
•The tube is centrifuged at 1300 rpm for
10 min (soft
•spin).
• A second centrifugation is performed at
2000 rpm for 10 min (hard spin)
•After blood collection, one can Wait for
10 min for centrifugation
•Preparation is labour intensive
Based on •Sudden fibrin polymerization‑depending
architecture on the amount of surgical additives
(thrombin and calcium chloride)
•Bilateral junctions (condensed tetra
molecular) are constituted with strong
thrombin concentrations and allow the
thickening of fibrin polymers leading to
the constitution of a rigid network,
unfavorable to cytokine enmeshment and
cellular migration
Second generation ‑ PRF
•No anticoagulants are used
•Single spin centrifugation
•The tube is centrifuged at 3000
rpm for 10 min
•It involves speedy blood collection
and immediate centrifugation
•Simple and cost effective
•Slow natural polymerization on
contact with glass particles of the
test tube results in physiologic
thrombin concentration
•Equilateral junctions (connected
trimolecular) This 3‑dimensional
organization gives great elasticity
tothe fibrin matrix which is
observed in a flexible, elastic and
very strong PRF membrane
Theoretical computer modeling
of condensed
tetramolecular junctions
Platelet trapped in the fibrin gel
Platelet cytokine in solution
Theoretical computer modeling
of trimolecular junctions
•Cytokine intrinsically retained
within fibrin fibrillae
•Platelet cytokine in solution
(extrinsically associated with
fibrin polymers)
•Fibrin‑associated glycanic chains
•Circulating glycoproteins
(fibronectin)
•Fibrin fibrilla associate with
glycanic chains and intrinsic
cytokines
 Based on biological There is Immediate Growth factors are
property release of growth factors released slowly over a
period of 7 or more days

Based on Concern over the use of No coagulopathies and no

therapeutic concern bovine thrombin, bovine bleeding episodes
factor Va may be a An in vitro study showed
contaminant in certain that PRF is superior to PRP,
bovine considering the
thrombin commercial expression of alkaline
preparations, antibodies phosphatase and induction
to bovine factor Va may of mineralization, caused
cross react with human markedly by release of
factor Va and may produce TGF‑β, and PDGF‑AB
coagulopathies and rare
bleeding episodes

Bansal S, Garg A, Khurana R, Chhabra P. Platelet-rich fibrin or platelet-rich plasma–which one is better? an opinion. Indian Journal of Dental
Sciences. 2017 Sep 1;9(5):49.
 Merits of PRF
•Ease of preparation/application
•Lack of biochemical modification
•Simplified and cost effectiveprocess
•Long‑term effect
•Able to support cytokines enmeshment and
cellular migration
•Increased incorporation of the circulating
cytokines in the fibrin meshes (intrinsic
cytokines)
•It is an immune organizing node
•It supports and accelerates the healing
process due to slow polymerization
•Helps in hemostasis
•Three‑dimensional structure gives elasticity
and flexibility to PRF Membrane
Demerits of PRF
•Low quantity of PRF is obtained,because of
autologous blood so application in general
surgery is limited.
•The clinical benefit of PRF depends on time
interval between speed of handling between
blood collection and centrifugation as PRF is
prepared without any addition anticoagulants
•The fibrin matrix contains the circulating
immune cells and all the highly antigenic
plasmatic molecules, that is why PRF is totally
specific to the donor
•PRF membrane should be used immediately
after preparation as it will shrink resulting in
dehydration altering the structural integrity of
PRF and leukocyte viability will be adversely
affected altering its biologic properties.
•PRF when stored in refrigerator can result in
risk of bacterial contamination
 Merits of PRP
•Soft autologous preparation, free from
concerns over transmissible disease such
as HIV, hepatitis etc.
•Convenient for patient, blood is collected
in the immediate preoperative period
•Presence of platelets brings cytokines
and growth factors to the site of surgery
which helps in rapid regeneration in a
manner that would not occur with fibrin
glue
Demerits of PRP
•Concern over the use of bovine
thrombin, the fact that bovine thrombin
has been associated with development of
antibodies to clotting factors V, XI and
thrombin, which had occasionally lead to
life threatening coagulopathies
•Lack of uniformity in PRP preparation
protocol as different platelet
concentration has different storage time

Bansal S, Garg A, Khurana R, Chhabra P. Platelet-rich fibrin or platelet-rich plasma–which one is better? an opinion. Indian Journal of Dental
Sciences. 2017 Sep 1;9(5):49.
 Influence of PRF in the healing of bone and
gingival tissues. Clinical and histological
evaluations

Marrelli M, Tatullo M. Influence of PRF in the healing of bone and gingival tissues. Clinical and histological evaluations. Eur Rev Med Pharmacol
Sci. 2013 Jul 1;17(14):1958-62.
 Effect of Platelet Rich Fibrin (PRF) on Peri-implant Soft Tissue and Crestal Bone
in One-Stage Implant Placement: A Randomized Controlled Trial

• AIM:This prospective study evaluated the effect of Platelet PRF on peri-

implant tissue response following one-stage implant placement with non-
functional immediate provisionalization in maxillary anterior region.
• CONCLUSION:PRF could be considered as a healing biomaterial with
potential beneficial effect on peri-implant tissue and can be used as a
therapeutic adjuvant in clinical scenario of one stage, single tooth
implant placement procedure in maxillary anterior region.
 CONCLUSION
• PRF as a biologic surgical additive has been
successfully used for varied applications in dentistry.
• Technological advancements in the field of PRF such
as i-PRF have paved way for the versatility in the
applications of the platelet concentrates.
• With the increase in our understanding about the
biology of PRF, in future we can expect improved
additives which will further enhance the wound
healing experience.
 REFERENCES
• Gupta V, Bains VK, Singh GP, Mathur A, Bains R. Regenerative potential of platelet rich
fibrin in dentistry: Literature review. Asian J Oral Health Allied Sci. 2011 Jan 1;1:23-8.
• Shah R, Thomas R, Mehta DS. An Update on the Protocols and Biologic Actions of Platelet
Rich Fibrin in Dentistry. The European journal of prosthodontics and restorative dentistry.
2017 Jun;25(2):64-72.
• Tozum TF, Demiralp B. Platelet-rich plasma: a promising innovation in dentistry. Journal-
Canadian Dental Association. 2003 Nov;69(10):664-5.
• Marrelli M, Tatullo M. Influence of PRF in the healing of bone and gingival tissues. Clinical
and histological evaluations. Eur Rev Med Pharmacol Sci. 2013 Jul 1;17(14):1958-62.
• Huang FM, Yang SF, Zhao JH, Chang YC. Platelet-rich fibrin increases proliferation and
differentiation of human dental pulp cells. Journal of endodontics. 2010 Oct
1;36(10):1628-32.
• Borie E, Oliví DG, Orsi IA, Garlet K, Weber B, Beltrán V, Fuentes R. Platelet-rich fibrin
application in dentistry: a literature review. International journal of clinical and
experimental medicine. 2015;8(5):7922.
• Bansal S, Garg A, Khurana R, Chhabra P. Platelet-rich fibrin or platelet-rich plasma–
which one is better? an opinion. Indian Journal of Dental Sciences. 2017 Sep 1;9(5):49.
• Kang YH, Jeon SH, Park JY, Chung JH, Choung YH, Choung HW, Kim ES, Choung PH.
Platelet-rich fibrin is a Bioscaffold and reservoir of growth factors for tissue
regeneration. Tissue Engineering Part A. 2011 Feb 1;17(3-4):349-59.
• Maniyar N, Sarode GS, Sarode SC, Shah J. Platelet-Rich fibrin: A “wonder material” in
advanced surgical dentistry. Medical Journal of Dr. DY Patil Vidyapeeth. 2018 Jul
1;11(4):287.
• Verma A, Srivastava S, Khurshid S, Parveen F, Pandey P. Platelet rich fibrin: a promising
innovation in regenerative therapy. Journal of Evolution of Medical and Dental
Sciences. 2015 Apr 23;4(33):5748-57.
• Arora NS, Ramanayake T, Ren YF, Romanos GE. Platelet-rich plasma: a literature review.
Implant dentistry. 2009 Aug 1;18(4):303-10.
• Kaur P, Puneet VD, Dahiya V. Platelet-rich plasma: A novel bioengineering concept.
Trends Biomater Artif Organs. 2011 Apr 1;25(2):86-90.