1. Platelet rich fibrin (PRF) is a platelet concentrate developed as a simpler alternative to platelet rich plasma (PRP) that does not require biochemical handling of blood. 2. PRF involves collecting a patient's blood sample without anticoagulant and centrifuging it to obtain a fibrin clot containing platelets and growth factors between the red blood cells and plasma. 3. The fibrin matrix concentrates and protects platelets and growth factors that are slowly released over 1 month to stimulate soft and hard tissue healing through cell migration and proliferation.

1. Platelet rich fibrin: an autologous bioactive membrane

2. Review Article
Platelet rich fibrin: an autologous bioactive
membrane
Anirban Chatterjee a,
*, Prerna Agarwal b
, Shobha Krishna Subbaiah b
a
Sr. Consultant, Periodontist & Implantologyst, Apollo Hospital, Bangalore 560038, India
b
Consultant, Periodontist, Apollo Clinic, Bangalore 560038, India
a r t i c l e i n f o
Article history:
Received 26 December 2013
Accepted 30 January 2014
Available online 12 March 2014
Keywords:
PRF
PRP
Growth factors
a b s t r a c t
Platelet-Rich Fibrin (PRF) is a new second-generation platelet concentrate, with simplified
processing, and no biochemical blood handling. It has several advantages over traditionally
prepared PRP, which has been widely used for accelerating soft tissue and hard tissue
healing for years. Strictly autologous preparation, the amount of PRF obtained is limited,
includes its disadvantages. Choukroun’s PRF incorporates leucocytes, platelets and a wide
range of healing proteins within a dense fibrin matrix. It is a natural bioactive membrane,
which can enhance soft/hard tissue healing, at the same time, can also protect surgical
sites, grafted materials from external aggressions. This article describes the evolution of
this second-generation platelet concentrate and its multiple uses in various surgical
procedures.
Copyright ª 2014, Indraprastha Medical Corporation Ltd. All rights reserved.
1. Introduction
Regenerative potential of platelets was introduced in 1974,
and Ross et al1
were amongst the pioneers who first described
a growth factor from platelets. A new family of platelet
concentrate, which is neither a fibrin glue nor a classical
platelet concentrate, discovered in France because of legal
complications of biochemical blood handling. This new
biomaterial is called as PRF, looks like an autologous cicatricial
matrix.2
PRF is a fibrin matrix of trapped platelets, cytokines
and other cells, which are released after a certain time,3
to act
as a resorbable biomembrane. More recently, Gassling et al4
have shown that PRF is a suitable scaffold for breeding
human periosteal cells in vitro, which may be suitable for
bone tissue engineering applications.5
2. What is fibrin?
Fibrin is the activated form of a plasmatic molecule called
fibrinogen.6
This soluble fibrillary molecule is massively
present both in plasma and in the platelet a-granules and
plays a determining role in platelet aggregation during he-
mostasis. It is transformed into a kind of biologic glue
capable of consolidating the initial platelet cluster, thus
constituting a protective wall along vascular breaches dur-
ing coagulation. In fact, fibrinogen is the final substrate of
all coagulation reactions. Being a soluble protein, fibrinogen
is transformed into an insoluble fibrin by thrombin while
the polymerized fibrin gel constitutes the first cicatricial
matrix of the injured site.7e9
* Corresponding author. Tel.: þ91 9845003721.
E-mail address: dranirbanchatterjee@yahoo.com (A. Chatterjee).
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.elsevier.com/locate/apme
a p o l l o m e d i c i n e 1 1 ( 2 0 1 4 ) 2 4 e2 6
http://dx.doi.org/10.1016/j.apme.2014.01.007
0976-0016/Copyright ª 2014, Indraprastha Medical Corporation Ltd. All rights reserved.

3. 3. Biological aspect
PRF was developed in France by Choukroun et al10
Basically
the platelets and released cytokines are accumulated in a
fibrin clot. Platelet granules contain many platelet specific (eg.
beta-thromboglobulins) & non-platelet specific proteins (eg.
fibronectin, thrombospondin, fibrinogen, growth promoters,
fibrinolysis inhibitors, immunoglobulins etc), calcium and
serotonin etc.11
Growth factors released by alpha-granules
encompass a group of cytokine polypeptides with relatively
low molecular weight ranging from 6 to 45 kDa.12
After acti-
vation and degranulation platelets aggregates at the healing
site and release the cytokines (IL-1 beta, IL-6, tumor necrosis
factor (TNF)-alpha)13
and growth factors (transforming growth
factor (TGF) beta 1, platelet derived growth factor (PDGF),
vascular endothelial growth factor (VEGF), epidermal growth
factor (EGF)) that stimulates cell migration and proliferation
within the fibrin matrix and thus begins the first stage of
healing.11
According to Dohan et al13
PRF may decreases many
harmful effects at inflammatory site natural to surgical act
and thus could be an immune regulation node with inflam-
mation retro-control abilities and explained the reduction of
post-operative infections.
4. Platelet-rich fibrinda natural fibrin matrix
Platelet-rich fibrin (PRF) requires neither anticoagulant nor
bovine thrombin (nor any other gelling agent). It is nothing
more than centrifuged blood without any addition, which
makes it possible to avoid all the restrictions. The PRF protocol
is very simple: A blood sample is taken without anticoagulant
& immediately centrifuged at 3000 rpm for 10 min. Due to the
absence of anticoagulant, most of the platelets activates
within few minutes and release the coagulation cascades.
Acellular plasma is initially accumulated in the upper part of
the tube, before the circulating thrombin transforms it into
fibrin. A fibrin clot is then obtained in the middle of the tube,
just between the red corpuscles at the bottom and acellular
plasma at the top (Fig. 1).2
Quick handling is the only way to obtain a clinically usable
PRF clot. If the duration required to collect blood and launch
centrifugation is overly long, failure will occur: The fibrin will
polymerize in a diffuse way in the tube and only a small blood
clot without consistency will be obtained. In conclusion, the
PRF protocol makes it possible to collect a fibrin clot charged
with serum and platelets. By driving out the fluids trapped in
the fibrin matrix, practitioners will obtain very resistant
autologous fibrin membranes.2,10
5. Clinical implications
Choukroun et al10
were amongst the pioneers for using
autologous PRF to improve bone healing in implant dentistry.
They evaluate the potential of PRF in combination with freeze-
dried bone allograft (FDBA) to enhance bone regeneration in
sinus floor elevation and sinus floor augmentation. In their
study, PRF was added to FDBA particles (test group), and FDBA
without PRF was used (control group). In results they found,
the maturation & quantities of newly formed bone were
equivalent between the two groups.14
Mazor et al15
assessed
the relevance of PRF concentrate and biomembranes as the
sole filling material during a lateral sinus lift with immediate
implantation in a case series. From a radiologic and histo-
logical point of view at 6 months after surgery, they found a
high volume of regenerated bone in the subsinus cavity up to
the tip of the implants. Toffler et al16
advocated membrane
insurance by possibly sealing an undetected perforation dur-
ing lateral window osteotomy procedure using PRF mem-
brane. In a multicenteric study by Kfir et al,17
minimally
invasive antral membrane balloon elevation (MIAMBE) done
using PRF and bone substitutes, injected under the antral
membrane and implant placement along with primary
closure executed at the same sitting, revealed that MIAMBE
can be applied to all patients in need of posterior maxilla bone
augmentation with high procedural success, low complication
rate, and satisfactory bone augmentation and implant sur-
vival. Simonpieri et al18,19
reported maxillary reconstruction
using FDBA, PRF membranes and 0.5% metronidazole solution
in twenty patients case series. Toffler20
advocated osteotome-
mediated sinus floor elevation (OMSFE) or crestal core eleva-
tion (CCE)21
with simultaneous implant placement using PRF
plugs. Thick PRF plugs or small disks of 1 cm diameter can also
be easily inserted into the residual extraction sockets.16
Aroca
et al22
evaluate the modified coronally advanced flap alone or
in combination with PRF for the treatment of adjacent Miller
Class I and II multiple gingival recession, & discovered inferior
root coverage of about 80.7% as compared to about 91.5%
achieved at control site, but an additional gain in gingival/
mucosal thickness compared to conventional therapy.
6. Conclusion
Thus, with this article we can conclude that the new and
recent generation of platelet concentrate-PRF, would be a
good friend to Periodontists in the near future. It has a list of
its benefits, & intraoral applications. This material is already
being used widely in France, and considering its advantages,
its popularity should increase here too. More clinical, histo-
logical and statistical studies are now required to understandFig. 1 e Different layers after blood centrifugation.
a p o l l o m e d i c i n e 1 1 ( 2 0 1 4 ) 2 4 e2 6 25

4. the benefits of this new platelet concentrate better. However,
it cannot be ignored that since it is obtained from an autolo-
gous blood sample, the quantity of PRF produced is low and
only a limited volume can be used. This fact limits the sys-
tematic utilization of PRF, as in general surgery. Also though
the potential applications of PRF are broad, however, an ac-
curate working knowledge of the biomaterial, its biology, ef-
ficiency & limits are necessary to optimize its use in daily
practice. Hence additional randomized clinical trials evalu-
ating the use & performance of PRF are warranted.
Conflicts of interest
All authors have none to declare.
r e f e r e n c e s
1. Ross R, Glomset J, Kariya B, Harker L. A platelet-dependent
serum factor that stimulates the proliferation of arterial
smooth muscle cells in vitro. Proc Natl Acad Sci U S A.
1974;71:1207e1210.
2. Dohan DM, Choukroun J, Diss A, et al. Platelet-rich fibrin
(PRF): a second-generation platelet concentrate. Part I:
technological concepts and evolution. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod. 2006;101:e37ee44.
3. Mosesson MW. Fibrinogen and fibrin structure and functions.
J Thromb Haemost. 2005;3:1894e1904.
4. Gassling V, Douglas T, Warnke YA, Wiltfang J, Becker ST.
Platelet-rich fibrin membranes as scaffolds for periosteal
tissue engineering. Clin Oral Impl. 2010;21:543e549.
5. Anitua E, Sa´nchez M, Nurden AT, Nurden P, Orive G, Andı´a I.
New insights into and novel applications for platelet-rich
fibrin therapies. Trends Biotechnol. 2006;24:227e234.
6. Mosesson MW, Siebenlist KR, Meh DA. The structure and
biological features of fibrinogen and fibrin. Ann N YAcad Sci.
2001;936:11e30.
7. Clark RA. Fibrin and wound healing. Ann N Y Acad Sci.
2001;936:355e367.
8. Collen A, Koolwijk P, Kroon M, van Hinsbergh VW. Influence
of fibrin structure on the formation and maintenance of
capillary like tubules by human microvascular endothelial
cells. Angiogenesis. 1998;2:153e165.
9. van Hinsbergh VW, Collen A, Koolwijk P. Role of fibrin matrix
in angiogenesis. Ann N Y Acad Sci. 2001;936:426e437.
10. Choukroun J, Adda F, Schoeffler C, Vervelle A. Une
opportunite´ en paro-implantologie: le PRF. Implantodontie.
2001;42:55e62.
11. Dohan DM, Choukroun J, Diss A, et al. Platelet-rich fibrin
(PRF): a second-generation platelet concentrate. Part II:
platelet-related biologic features. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod. 2006;101:e45ee50.
12. Su CY, Kuo YP, Tseng YH, Su CH, Burnouf T. In vitro release of
growth factors from platelet-rich fibrin (PRF): a proposal to
optimize the clinical applications of PRF. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod. 2009;108:56e61.
13. Dohan DM, Choukroun J, Diss A, et al. Platelet-rich fibrin
(PRF): a second-generation platelet concentrate. Part III:
leucocyte activation: a new feature for platelet concentrates?
Oral Surg Oral Med Oral Pathol Oral Radiol Endod.
2006;101:e51ee55.
14. Choukroun J, Diss A, Simonpieri A, et al. Platelet-rich fibrin
(PRF): a second-generation platelet concentrate. Part V:
histologic evaluations of PRF effects on bone allograft
maturation in sinus lift. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod. 2006;101:299e303.
15. Mazor Z, Horowitz RA, Del Corso M, Prasad HS, Rohrer MD,
Dohan Ehrenfest DM. Sinus floor augmentation with
simultaneous implant placement using Choukroun’s platelet
rich fibrin as the sole grafting material: a radiologic and
histologic study at 6 months. J Periodontol. 2009;80:2056e2064.
16. Toffler M, Toscano N, Holtzclaw D, Corso MD, Dohan
Ehrenfest DM. Introducing Choukroun’s platelet rich fibrin
(PRF) to the reconstructive surgery milieu. J Implant Adv Clin
Dent. 2009;1:21e30.
17. Kfir E, Goldstein M, Yerushalmi I, et al. Minimally invasive
antral membrane balloon elevation e results of a
multicenter registry. Clin Implant Dent Relat Res. 2009;11(suppl
1):e83ee91.
18. Simonpieri A, Del Corso M, Sammartino G, Dohan
Ehrenfest DM. The relevance of Choukroun’s platelet-rich
fibrin and metronidazole during complex maxillary
rehabilitations using bone allograft. Part I: a new grafting
protocol. Implant Dent. 2009;18:102e111.
19. Simonpieri A, Del Corso M, Sammartino G, Dohan
Ehrenfest DM. The relevance of Choukroun’s platelet-rich
fibrin and metronidazole during complex maxillary
rehabilitations using bone allograft. Part II: implant
surgery, prosthodontics, and survival. Implant Dent.
2009;18:220e229.
20. Toffler M. Osteotome-mediated sinus floor elevation: a
clinical report. Int J Oral Maxillofac Implants. 2004;19:266e273.
21. Toffler M. Staged sinus augmentation using a crestal core
elevation procedure (CCE) to minimize membrane
perforation. Pract Proced Aesthet Dent. 2002;14:767e774.
22. Aroca S, Keglevich T, Barbieri B, Gera I, Etienne D. Clinical
evaluation of a modified coronally advanced flap alone or in
combination with a platelet-rich fibrin membrane for the
treatment of adjacent multiple gingival recessions: a 6-month
study. J Periodontol. 2009;80:244e252.
a p o l l o m e d i c i n e 1 1 ( 2 0 1 4 ) 2 4 e2 626

5. Apollohospitals:http://www.apollohospitals.com/
Twitter:https://twitter.com/HospitalsApollo
Youtube:http://www.youtube.com/apollohospitalsindia
Facebook:http://www.facebook.com/TheApolloHospitals
Slideshare:http://www.slideshare.net/Apollo_Hospitals
Linkedin:http://www.linkedin.com/company/apollo-hospitals
Blog:Blog:http://www.letstalkhealth.in/