CLINICAL
A comprehensive clinical review of Platelet Rich Fibrin
(PRF) and its role in promoting tissue healing and
regeneration in dentistry. Part III: Clinical indications of
PRF in implant dentistry, periodontology, oral surgery
and regenerative endodontics
Johan Hartshorne1 and Howard Gluckman2
Summary
1
Johan Hartshorne B.Sc.,
B.Ch.D., M.Ch.D, M.P.A. Ph.D.
(Stell), FFPH.RCP (UK),
General Dental Practitioner,
Intercare Medical and Dental
Centre, Tyger Valley, Bellville,
7530. South Africa. E-mail:
[email protected]
2
Howard Gluckman BDS.,
M.Ch.D. (OMP) (Wits) Specialist
In Periodontics and Oral
Medicine, Director of The Implant
and Aesthetic Academy,
Cape Town, South Africa.
E-mail: [email protected]
The purpose of Part III of this review is to analyse the available literature and clinicalbased evidence on PRF relating to its clinical indications in implant dentistry,
periodontics, oral surgery and regenerative endodontics. An improved understanding
of the clinical indications of PRF will facilitate the clinicians’ ability to enhance the
therapeutic applications of PRF in these fields. PRF is increasingly being investigated
and used world-wide by clinicians as an adjunctive autologous biomaterial to promote
bone and soft tissue healing and regeneration. PRF has also grabbed the attention of
clinicians world-wide 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. 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, and when combined and prepared properly, in whichever
form, are involved in the key processes of tissue healing and regeneration. PRF is
widely being used with promising results in various clinical applications with the primary
aim of promoting wound healing, accelerating graft maturation, decreasing the healing
period, protecting and promoting improved outcomes in soft tissue and bone healing,
and tissue regeneration. PRF combined with GBR procedures offers several added and
synergistic advantages including promoting wound healing in compromised wound
healing situations, bone growth and maturation, graft stabilization, wound sealing and
hemostasis, and improving the handling properties of graft materials. PRF added to, or
combined with bone substitutes, offer an effective and easy way for managing and/or
augmenting peri-implant osseous defects, sinus floor elevations, intrabony defects, fresh
extraction sockets and alveolar ridges with deficient or atrophied alveolar bone. PRF
membranes used as a protective or wound bandage on connective tissue harvesting
sites (palate) or donor sites (vestibule), significantly accelerates wound healing and
reduces post-operative pain and discomfort. The use of PRF in revitalization,
revascularization, and regenerative pulp therapies are currently attracting a lot of
attention and several case studies in the field of regenerative endodontics are being
reported.
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. Irrespective
64 INTERNATIONAL DENTISTRY – AFRICAN EDITION VOL. 6, NO. 5
CLINICAL
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. The clinical
effectiveness of different PRF preparation protocols in various
clinical settings remains to be validated through independent
robust RCT’s.
Introduction
The prospect of having new therapies, biomaterials and
bioactive surgical additives available that will improve
success and predictability of patient outcomes in soft and
bone tissue healing and regeneration are key treatment
objectives in dental implantology, periodontology and oral
surgery.
Platelet Rich Fibrin (PRF), a patient blood-derived and
autogenous living biomaterial, is increasingly being
investigated and used worldwide by clinicians as an
adjunctive autologous biomaterial to promote bone and soft
tissue healing and regeneration. 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.1 These key elements are all active
components of PRF, and when combined and prepared
properly are involved in the key processes of tissue healing
and regeneration, including cell proliferation and
differentiation, extracellular matrix synthesis, chemotaxis and
angiogenesis (neo-vascularization).2,3 An improved
understanding of the development, biological and
physiological properties and characteristics of PRF in tissue
healing and regeneration over the last two decades, has led
to more successful therapeutic applications, especially in the
fields of dental implantology, periodontology and oral surgery.
The purpose of this comprehensive review is to analyse the
available scientific literature on PRF regarding its: (Part I) (i)
definition and purpose in the clinical environment; (ii)
development and classification of platelet concentrate
biomaterials; (iii) biological characteristics and composition;
(Part II) (iv) preparation technique; (v) optimizing quality; (vi)
physical application and handling; and (vii) the benefits and
limitations of PRF; and (Part III) (viii) its clinical indications in
implant dentistry, periodontics, oral surgery and regenerative
endodontics.
Methodology, Search strategy and inclusion criteria
An electronic MEDLINE (PubMed) and Google Scholar
search was performed for all articles on Platelet Rich Fibrin
(PRF) and Platelet concentrates up to May 2016. The search
was complimented by an additional hand search of selected
journals in oral implantology, oral surgery and periodontal,
as well as grey literature. The reference lists and
bibliographies of all included publications were also
screened for relevant studies. The search was limited to the
English language. Randomized controlled trials (RCT’s),
controlled clinical trials (CCT’s), case reports, case series,
prospective, retrospective and in-vitro/in vivo studies were
included in the narrative review. Only RCT’s, CCT’s, and
systematic reviews were used for evaluating evidence-based
data (Tables 1, 2, 3). Animal studies were excluded from
this review.
Where and how can I use PRF?
A general rule of guidance is to use PRF in surgical situations
where protection and stimulation of healing and regeneration
is critical and where the prognosis for tissue repair is poor
or potentially compromised in the absence of a tissue
regeneration scaffold and addition of growth factors.
Implant dentistry
Most of the PRF clinical research in implantology is currently
focused in the fields of improving clinical outcomes with sinus
floor elevations using PRF as sole grafting material,
simultaneous with implant placement, 4,62 or SFE
using a combination of PRF and bone allograft (FDBA)
prior to implant placement.5,6 Other focus areas of clinical
implantology research are use of PRF in alveolar ridge
preservation (socket augmentation) 7, peri-implant tissue
healing 8, and improving implant stability. 9 (Table 1)
In-vitro studies have shown PRF-induced gene expression
of the early and late markers of osteogenesis, stimulates bone
and soft tissue healing.10 This finding suggests that PRF is
indicated in numerous clinical applications, such as, socket
augmentation, jump gap filling during immediate extraction
and implant placement, and stimulation of bone and soft
tissue healing during bone augmentations or during sinus
elevation.
•
Sinus floor elevation using PRF as sole or
combination graft biomaterial
A systematic review showed that PRF used as a sole filling
material in SFE with simultaneous implant placement is a
simple technique with promising results.4,11 Various clinical
case reports describe the lateral approach for sinus floor
elevation using only PRF as the grafting material.12,13,14
(Figure 1a, 1b & 1c)
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Table 1. Evidence-based literature on the use of PRF in implant dentistry
Application
Reference
Type of Study
Evidence / Conclusion†
Sinus floor elevation
Ali S, Bakry SA,
Abd-Elhakam,
2016 4
Systematic
review
PRF as a sole filling material for sinus lift with simultaneous implant
placement is a simple technique with promising results. Addition
of PRF to DFDBA accelerates graft maturation and decreases the
healing period before implant placement. PRF membranes
represent an easy and successful method to cover sinus
membrane or osteotomy window.
Socket Augmentation
Hauser F,
Gaydarov N,
Badoud I et al.,
20137
RCT
Use of PRF membranes to fill the socket after tooth extraction led
to improved alveolar bone healing and better preservation of the
alveolar crest width. These results support the use of a minimally
traumatic procedure for tooth extraction and socket filling with
PRF to achieve preservation of hard tissue.
Peri-implant stability
and healing
Öncü E,
Alaaddinoõglu E,
20159
CCT
Results of this study demonstrated that PRF application into the
osteotomy site increases implant stability during the early healing
period. Simple application of this material seems to provide faster
osseointegration.
Peri-implant tissue
healing
Boora P, Rathee
M, Bhoria M. ,
20158
Pre-implantology
sinus floor elevation
Choukroun J, Diss
A, Simonpieri A, et
al (Part 5) 20065
CCT
Sinus floor augmentation with FDBA and PRF leads to a reduction
of healing time prior to implant placement. From a histologic point
of view, this healing time could be reduced to 4 months.
Pre-implantology
sinus elevation
Tatullo M, Marrelli
M, Cassetta M, et
al, 20126
CCT
PRF together with deproteinized bovine bone (Bio-Oss) and
piezosurgery favors optimal bone regeneration compared to bone
graft material alone. At 106 days, it is already possible to achieve
good primary stability of endosseous implants, though lacking of
functional loading. PRF favors clot stability and the membranous
shape allows creating a natural “barrier effect” on the bone
breaches that were opened in the surgical areas.
RCT
PRF can be considered as a healing biomaterial with potential
beneficial effect on peri-implant tissue and can be used as a
therapeutic adjuvant in the clinical scenario of one stage, single
tooth implant placement procedure in maxillary anterior region.
† Within the limitations of the studies, and more and large samples rigorous clinical trials are required to validate the evidence.
The PRF membrane is recommended as an inexpensive
and easily handled substitution biomaterial during sinus
elevation, to reduce the healing time before loading. It is a
cheap and easily handled material with healing properties.
Its fibrin matrix properties and ability of slowly releasing
Figure 1a: PRF used as sole grafting
material in lateral window sinus floor
elevation.
growth factors makes it an ideal replacement biomaterial to
replace xenogenic and expensive collagen membranes in
some situations.12
The review also suggests that PRF combined with a bone
allograft or other bone substitutes, accelerates graft
Figure 1b: Multiple layers of PRF used for
sinus floor elevation.
66 INTERNATIONAL DENTISTRY – AFRICAN EDITION VOL. 6, NO. 5
Figure 1c: Sinus osteotomy covered with
a collagen membrane.
HARTSHORNE
Figure 2a: Lateral window osteotomy
ready for sinus floor elevation.
Figure 2c: Sinus floor grafted with
xenograft mixed with PRF fragments.
Figure 2b: Sinus floor elevated and
grafted with simultaneous implant placed
Figure 2d: Lateral window sinus
osteotomy covered with a collagen
membrane.
maturation and decreases the healing period before implant
placement.4 (Figure 2a – 2e) The latter finding has also been
confirmed by other clinical trials and case studies. 5,6,15,16
Various case studies have demonstrated that PRF
membranes can be used successfully as a protective barrier
to cover the sinus membrane during grafting procedures.
4,6,12,17,18,19
(Figure 3)
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.4,12,17,20
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.17,18
Figure 2e: PRF membrane (double layer)
draped over the collagen membrane to
facilitate soft tissue wound healing.
therapeutic alternative for implant site preparation.24
Alternatively, PRF can also be mixed with a bone substitute
to fill the socket, and used as a protective cover over the
grafted socket. (Figure 4a - 4g) This is particularly important
when gingival wound closure is impossible or difficult with
the sutures.25 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.25
• Alveolar ridge preservation (socket augmentation)
for early or late implant placement
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.7 PRF plugs or
membranes can also be used to fill extraction sockets, even
when associated with compromised extraction sockets21,
severe cystic destructions or after cyst enucleations,22,20,23 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
Figure 3: PRF membrane used a protective barrier to cover the
sinus membrane (Schneiderian membrane) before grafting.
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Figure 4a: Fresh extraction socket
curetted and ready for augmentation.
Figure 4b: PRF fragments placed into the
socket.
Figure 4c: Bone putty alloplast injected
into the socket.
Figure 4d: Plugger used to condense PRF
fragments and bone putty into the socket.
Figure 4e: PRF plug placed on top of the
bone putty.
Figure 4f: Socket closed with PRF plug
and used as a protective cover over the
grafted socket.
Figure 4g: Provisional removable prosthesis with ovate pontic seated over the
grafted socket.
• Immediate postextraction implant placement and
jump-gap augmentation – Peri-implant healing
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.
8,119
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.26 (Figure 5a
& 5b) In the latter case study it is suggested that the
augmented jump gap is covered with cross-linked collagen
membrane, overlayed by a double layer of PRF and the flap
closed by sutures. 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.8,27 (Figure 6a - 6c) 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. (Figure 7a & 7b)
• 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 a 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.20,28,29, 30
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Figure 5a: Residual root to be extracted for immediate implant
placement.
Figure 5b: Jump gap between implant and socket defect
grafted with xenograft mixed with PRF fragments and covered
with a PRF membrane.
PRF has also been successfully used to treat fenestration
defects around implants.31 PRF membrane cut in pieces
(Figure 8), or platelet liquid (I-PRF) (Figure 9) 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. 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.
PRF added to the maintenance of the graft homeostasis due
to release of growth factors, thus contributing to the successful
outcome of treatment.33
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.32 In another study a successful treatment outcome was
also reported after debridement and detoxification with a
Cr,CR:YCGG later, 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. The authors concluded that the use of
Figure 6a: Implant site ready to be
draped with PRF membrane.
• Augmentation of alveolar ridges (horizontal and
vertical) and buccal bone defects (GBR)
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,6,29, ,34,35,36,37,38,39 and in cases of the severely
resorbed posterior mandible.40 The latter authors suggest that
three layers of L-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
remodeling. Periosteal incisions were done on the flaps to
promote their tension-free closure.40 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
30
combinations. PRF liquid (i-PRF) can be injected, or PRF
membrane placed above the GBR or GTR membrane to act
as a interposition barrier to protect and stimulate the bone
compartment, and as a healing membrane in order to
Figure 6b: PRF membrane draped around
an implant to stimulate bone and gingival
healing.
70 INTERNATIONAL DENTISTRY – AFRICAN EDITION VOL. 6, NO. 5
Figure 6c: Flap sutured.
HARTSHORNE
Figure 7a: PRF membrane draped over the healing abutment
to stimulate bone and gingival healing.
Figure 7b: Flap closure over PRF membrane and around
healing abutment.
improve the soft tissue healing and remodeling, and thus
avoid soft tissue dehiscence.25,40
overlaid with a double layer of PRF membranes. (Figure 10a
- 10c) These membranes were used as competitive
interposition barrier to protect and stimulate the bone
compartment, and as healing membranes to stimulate the
periosteum and gingival healing and remodeling. Periosteal
releasing incisions are done on the flaps to promote their
tension-free closure.40
Guided bone regeneration
Place harvested autogenous bone adjacent to the implant of
defect that requires grafting. The next layer is made up of a
mixture of bone grafting material with i-PRF or PRF membrane
or clot cut in small pieces. 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. 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
Figure 8: PRF membrane fragments mixed with bone particulate
can be used successfully to augment alveolar ridge defects
using GBR principles.
• Increasing implant stability and osseointegration
Case studies suggest that PRF application into the
osteotomy site (Figure 11a -11c) increases implant stability
during the early healing period, as evidenced by higher ISQ
values. Simple application of this material also seems to
provide faster osseointegration.9
Periodontal surgery
Most of the clinical research in periodontology is currently
Figure 9: i-PRF mixed with bone particulate can be used
successfully to augment alveolar ridge defects using GBR
principles.
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Table 2. Clinical evidence on the use of PRF in periodontology
Application
Reference
Type of
Study
The addition of autologous platelet concentrate (PRP and PRF) to open flap
Meta-analysis debridement (OFD) may improve clinical parameters: horizontal and
vertical clinical attachment level, probing depth and level of gingival margin
in the treatment of mandibular class II furcation defects compared to OFD
alone.
Furcation defects
Troiano G, Laino L,
Dioguardi M, et al,
2016 15
Furcation defects
Sharma et al. 2011b
Recession defects
Moraschini V,
dos Santos E, Barboza
P., 2015 66
Recession defects
Evidence / Conclusion†
45
Keceli HG, Kamak G,
Erdemir EO,
et al. , 2015 67
RCT
Significant improvement with PRF implies its role as a regenerative material
in treatment of furcation defects.
Meta- analysis
The results suggest that the use of PRF membranes did not improve the root
coverage, keratinized mucosa width, or clinical attachment level of Miller
class-I and -II gingival recessions compared to the other treatment
modalities.
RCT
The addition of PRF did not further develop the outcomes of coronally
advance flap combined with a connective tissue graft treatment except
increasing the tissue thickness.
Recession defects
Rajaram V, Thyegarajan R,
Balachandran A, et al,
2015 68
Intrabony defects
The meta-analysis showed clinically significant improvements in periodontal
Shah M, Deshpande N, Meta-analysis
parameters such as clinical attachment levels and intra-bony defect
41
Bharwani A, , 2014
reduction, and reduction in probing depth when IBDs were treated with PRF
alone when compared to OFD.
Intrabony defects
Gamal AY, Ghaffar
KAA, Alghezwy OA.,
2016 42
Intrabony defects
Intrabony defects
Intrabony defects
Intrabony defects
Intrabony defects
Intrabony defects
Palatal bandage
RCT
RCT
Shah M, Patel J, Dave
D, Shah S , 2015 43
PRF has shown significant results after 6 months, which are comparable to
DFDBA for periodontal regeneration in terms of clinical parameters. PRF has
several advantages when used as a graft material for infrabony defects.
RCT
Greater pocket depth reduction and periodontal attachment level (PAL) gain,
and bone fill at sites treated with PRF combined with conventional open-flap
debridement compared to conventional open-flap debridement alone.
RCT
The use of autologous PRF or PRP was effective in the treatment of 3-wall
IBDs with uneventful healing of sites. Treatment with autologous PRF or PRP
stimulated a significant increase in the PD reduction, GML, and bone fill
compared with OFD at 9 months.
46
Bansal C and Bharti V,
2013 47
CCT
RCT
Thorat MK, Pradeep
AR, Pallavi B., 2011
48
Pradeep AR, Bajaj P,
Rao NS, et al 2012
49
Femminella B, Iaconi MC,
Di Tullio M, 2016. 76
PRF and PRGF platelet concentrate failed to augment the clinical effects
achieved with the xenograft alone in treating intrabony defects. Periodontal
defects could not retain extra-physiologic levels of GF suggested to be
associated with platelet concentrate.
RCT
Sharma et al. 2011a44
Pradeep AR, Rao NS,
Agarwal P, et al, 2012
The additional application of PRF failed to improve root coverage after
double lateral sliding bridge flap in Miller’s Class I and II defects.
RCT
RCT
PRF combined with demineralized-freeze dried bone allograft (DFDBA)
demonstrated better results in probing pocket depth reduction and clinical
attachment level gain as compared to DFDBA alone in the treatment of
periodontal intrabony defects.
Greater reduction in pocket depth, more clinical attachment level gain and
greater intra-bony defect fill at sites treated with PRF compared to open flap
debridement alone.
PRF when added to porous hydroxyapatite (HA) increases the regenerative
effects observed with PRF in treatment of human three-wall intra-bony
defects.
The PRF-enriched palatal bandage significantly accelerates palatal wound
healing and reduces the patient’s morbidity.
† Within the limitations of the studies, and more and large samples rigorous clinical trials are required to validate the evidence.
74 INTERNATIONAL DENTISTRY – AFRICAN EDITION VOL. 6, NO. 5
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Figure 10a: Using PRF fragments mixed
with autogenous bone to fill spaces in
guided bone regeneration procedure.
Figure 10b: Bone graft covered with
collagen membrane.
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. (Table 2)
Intrabony and furcation periodontal defects
The regenerative and wound healing effects have been very
promising with PRF treating intrabony defects,
41,42,43,44,45,46,47,48,49,50,51
(Table 3) The abovementioned
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, 41,44,46,47,48,49,52,53,54,55,56,66 and furcation
lesions.45,57,58,59,60,61
Another study has also reported on using PRF successfully
as a regenerative material in cases of aggressive
periodontitis.60
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. Surgical
reconstructive therapy with placement of PRF in angular
defects can is suggested as an effective approach to
enhance periodontal regeneration.60
Platelet gel acts as a stabilized blood clot and therefore
recommended as a perfect filling material for natural tissue
regeneration and healing.25 Clinically, the general concept
of “Natural Tissue Regeneration” (NTR) and Natural Bone
Regeneration (NBR)25 requires to fill the periodontal intrabony
defect with L-PRF, most times in association with a bone
substitute used as a solid space maintainer, and then to cover
the filled intrabony defect with L-PRF membranes, used for the
protection of the grafted area and as a healing booster for
the soft tissues above the defects.25 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
Figure 10c: Bone graft and collagen
membrane covered with multiple PRF
membranes.
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.25 The NTR protocol25 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 has yet to be determine 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.12,119
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. (Figure 12a & 12b)
In comparison to GTR membranes, PRF will undergo a
quicker remodeling in situ than a resorbable collagen
membrane, but will promote a strong induction on the
periosteum and gingival tissue due to the slow release of
growth factors and other matrix proteins.63,64,65
GTR membranes are cell-proof barriers, whereas a PRF
membrane is a highly stimulating matrix, attracting cell
migration and preferential differentiation allowing new blood
vessel formation within the matrix, and also reinforcing the
natural periosteal barrier. The hard and soft tissues migrate
and interact within the PRF matrix. The PRF matrix becomes
the interface between the tissues and therefore avoids the
migration of the soft tissues deeper within the grafted defect
or augmented site. This biological characteristic is referred
to as a competitive barrier.64
These bioactive interactions are very important during
tissue regeneration, since the periosteum covers the internal
part of the gingival flap and is a key actor of bone healing
and gingival maturation. While GTR membranes block the
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Figure 11a: PRF inserted into an osteotomy site before placing
the implant to facilitate bone healing.
Figure 11c: Implant is inserted into the socket containing the
PRF membrane
Figure 11b: Implant wetted with PRF exudate containing growth
factors.
periosteum healing potential and bone/gingival interactions,
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.62
Palatal bandage
Recession defects and guided tissue regeneration (GTR)
The clinical evidence is less promising with the treatment
of recession defects.66,67,68 (Table 2) 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.
However, cases have been reported where PRF was
successfully used for treating localized, 64,69,70,71,72,73 and
multiple74 gingival recessions. Another 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
biotype.75
PRF membranes can also be used as a palatal wound
bandage or protection membranes after harvesting
connective tissue grafts in the palate.76,77,78 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.78,79,80
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.81 The reconstructed
papilla in the new position was stable when reviewed at 3
and 6 months postoperatively.
Oral Surgery
Most of the evidence-based research in the field of oral
76 INTERNATIONAL DENTISTRY – AFRICAN EDITION VOL. 6, NO. 5
HARTSHORNE
Figure 12a: Intrabony defect after root planning and soft laser
decontamination, filled with bone putty and covered with a PRF
membrane to protect the grafted site area and to facilitate bone
and soft tissue healing.
Figure 12b: Closure of flap over the grafted intrabony defect.
surgery is primarily focused on enhancing bone healing
82,83,84
and reducing postoperative complications following
3rd molar extractions. 82,85,86 (Table 3) Research is also
emerging on promoting healing of apico-marginal defects in
root end surgery. (Table 3) Numerous case and case series
studies have been reported that support the use of PRF in
various clinical applications in the field of oral surgery.
medication presenting a risk of osteonecrosis of the jaws, or
patients receiving anticoagulants.93
Delayed or compromised healing of extraction sockets is
mostly related to an unstable blood clot within the socket. In
such case a fibrin clot is simply placed in the socket, covered
with a collagen plug or membrane and sutured. Placing PRF
in a socket could amplify the natural coagulation process
and enhance socket healing.7, 24,93, 83,84,88, 89,90,91,92
• Post-extraction socket augmentation and healing
The healing and remodeling of an extraction socket is
highly dependent on the initial stabilization of the blood clot
and the quick gingival wound closure. This can be achieved
by placing fibrin plug in the socket (with or without a bone
substitute) and closing with a fibrin membrane. The use of
PRF as a post extraction sockets filling biomaterial is
recommended as a useful procedure in order to reduce the
early adverse effects of the inflammation, such as
postoperative pain,82,85,86 and to promote the soft tissue
healing and bone regeneration process.87
Clinical situations where post-extraction socket
augmentation with PRF is specifically indicated are for early
or delayed implant placement; and immediate post-extraction
implant placement.7,20 ,21,24,26,83,88,89,90,91,92
• Reduce post-extraction complications in medically
compromised cases
PRF can be used to minimize post-extraction complications
such as, osteitis, dry or infected sockets resulting from and
delayed or potentially compromised healing or bleeding
situations in systemic conditions such as such as with
diabetics; patient’s receiving on oral bisphosphonate
• Prevention of periodontal complications in 3rd molar
surgery
Complex third molar extractions frequently result in critical
size bone defects and compromised healing impacting
negatively on the outcome of periodontal tissues distal of the
second molar. When bone defects after extraction are
critical-sized (and often associated with cystic lesions), Using
PRF as a filling material or mixing PRF with a bone substitute
in order to use a significant volume of solid biomaterial for
filling is considered as reliable option. These treatments are
however no more simple dental extractions, and are often at
the border of guided bone regeneration (GBR) or bone
grafting. The use of a PRF as a filling material significantly
promotes soft tissue healing and also faster
regeneration of bone in these sites and neighboring
periodontal tissues.84,94,95
• Closing oro-antral fistulas
Oro-antral communications can complicate dental surgery,
particularly during extraction of a posterior maxillary root.
PRF clots can be used successfully for atraumatic or minimal
intervention closure of oro-antral communications, thus
78 INTERNATIONAL DENTISTRY – AFRICAN EDITION VOL. 6, NO. 5
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Table 3. Evidence-based literature on the use of PRF in oral surgery
Application
Reference
Type of Study
Evidence / Conclusion†
Reducing
complications in
3rd molar
extractions
Reference
Eshghpour et al,
201485
RCT
PRF application may decrease the risk of alveolar osteitis
development after mandibular third molar surgery.
Enhance bone
healing after 3rd
molar extractions
Gürbüzer B,
Pikdöken L, Tunalı
M, et al, 201083
CCT
PRF might not lead to enhanced bone healing in soft tissue
impacted mandibular third molar extraction sockets 4 weeks
after surgery.
Bone regeneration
after 3rd molar
extractions
Rao SG, Bhat P,
K. S. Nagesh KS,
et al, 2013 84
CCT
PRF accelerate regeneration of bone after third molar
extraction surgery in cases treated with PRF as compared to
the control group post operatively.
Bone healing and
post-operative
complications after
3rd molar surgery
Singh A, Kohli M,
Gupta N, 201282
Post-operative
Uyanık LO,
complications
Bilginaylar K,
following 3rd molar Etikan I., 201586
extractions
Root-end surgery /
Healing of
apico-marginal
defects
Dhiman M, Kumar
S, Duhan J, et al
2015.102
CCT
PRF is a valid method in promoting and accelerating soft and
hard tissue wound healing and regeneration, and decreasing
pain in mandibular 3rd molar extractions.
CCT
PRF and combination use of PRF and piezosurgery have
positive effects in reducing postoperative complications (pain
and trismus) after impacted third molar surgery.
A high success rate may be attained in apico-marginal defects
with endodontic microsurgery, and addition of PRF may not
necessarily improve the outcome.
RCT
† Within the limitations of the studies, more and large sample rigorous clinical trials are required to validate the evidence
eliminating the need to raise mucoperiosteal buccal sliding
flaps.96 The technique for closure of an oro-antral fistula using
platelet-rich fibrin is described by Argawal and co-workers.97
• Other oral surgical applications where PRF is used
Alveolar cleft grafting
The use of PRF has also been reported in other therapies
including: alveolar cleft grafting.106
• Apical / root end surgery
PRF clot (gel) serves as an ideal scaffold in root-end
surgical procedures to enhance soft tissue healing and bone
regeneration. 98,99,100,101 Other researcher’s report that PRF
may not necessarily improve the outcome of treatment. 102
The combination of PRF membrane as a matrix and MTA can
prove to be an effective alternative for creating artificial rootend barriers and to induce faster peri-apical healing with
large periapical lesions.103 It is suggested that the
combination of PRF and β-TCP for bone augmentation in
treatment of periapical defects is also a more effective at
increasing healing time compared to using bone substitute
material alone.104 PRF combined with an alloplastic bone
substitute has been successfully used for the management of
combined endodontic-periodontal lesions.105
Bisphosphonate related oral necrosis of the jaw
Recent case reports suggested that PRF might stimulate
gingival healing and act as a barrier membrane between
alveolar bone and the oral cavity, therefore offering a simple,
though effective treatment for the closure of bone exposure
in BRONJ. 107,108,109,120
Compromised wound healing situations (Diabetics)
PRF has also been used as an adjuvant in the
management of problematic chronic wounds.109 The
authors have shown that growth factors in PRF are
protected from proteolytic degradation. This may be
advantageous in the treatment of chronic wounds
characterized by high proteinase activity.
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Regenerative endodontic therapy
Regenerative endodontic procedures are widely being added
to the current armamentarium of pulp therapy
procedures.105,110,111,112,113,114
These biologically based procedures are designed to
restore function of a damaged and non-functioning pulp by
stimulation of existing dental pulp stem and progenitor cells
present in the root canal under conditions that are favorable
to their differentiation.110,111
• Management of open apex
Recent case reports have shown that the combined use of
platelet-rich fibrin (PRF), and mineral trioxide aggregate (MTA)
as root filling material is beneficial for the endodontic
management of an open apex. 112,115,116
It is hypothesized that the combination of MTA and PRF may
have a synergistic effect on the stimulation of odontoblastic
differentiation of stem cells.
• Revascularization and revitalization
Revascularization is the most studied and successful
approach of regenerative endodontics.115 Revitalization of
necrotic infected immature tooth is possible under conditions
of total canal disinfection combined with the additive effect
of PRF. 117,118 PRF is proposed as an ideal biomaterial for pulpdentin complex regeneration because it is a potentially valid
scaffold material containing leukocyte and growth factors to
facilitate tissue healing and regeneration in immature necrotic
teeth in children. 115,116,117
Repair and regenerative potential of PRF, and enhanced
cellular metabolism with laser bio stimulation, in combination
with the sealing ability of MTA enhances the clinical success
outcomes in pulpotomy and apexification procedures.115
Revitalization, revascularization, and regenerative pulp
therapies still needs to be validated with robust clinical trials.
Conclusion
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. 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
in various clinical applications in dental implantology,
periodontology, maxillofacial and oral surgery, and lately in
regenerative endodontics, to promote wound healing and
tissue regeneration. The use of PRF in revitalization,
revascularization, and regenerative pulp therapies are
currently attracting a lot of attention and several case studies
in the field of regenerative endodontics are being reported.
These applications however still need to be validated with
robust clinical trials.
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 it
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. 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 with improved successful and predictable
outcomes for the benefit of the patient. 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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of an oro-antral communication with platelet-rich fibrin. The
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Accepted
30
September
2015
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