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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
The purpose of Part III of this review is to analyse the available literature and clinical-
based 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
1
Johan Hartshorne B.Sc., synergistic advantages including promoting wound healing in compromised wound
B.Ch.D., M.Ch.D, M.P.A. Ph.D. healing situations, bone growth and maturation, graft stabilization, wound sealing and
(Stell), FFPH.RCP (UK),
hemostasis, and improving the handling properties of graft materials. PRF added to, or
General Dental Practitioner,
combined with bone substitutes, offer an effective and easy way for managing and/or
Intercare Medical and Dental
augmenting peri-implant osseous defects, sinus floor elevations, intrabony defects, fresh
Centre, Tyger Valley, Bellville,
7530. South Africa. E-mail: extraction sockets and alveolar ridges with deficient or atrophied alveolar bone. PRF
jhartshorne@kanonberg.co.za membranes used as a protective or wound bandage on connective tissue harvesting
sites (palate) or donor sites (vestibule), significantly accelerates wound healing and
2
Howard Gluckman BDS., reduces post-operative pain and discomfort. The use of PRF in revitalization,
M.Ch.D. (OMP) (Wits) Specialist revascularization, and regenerative pulp therapies are currently attracting a lot of
In Periodontics and Oral attention and several case studies in the field of regenerative endodontics are being
Medicine, Director of The Implant reported.
and Aesthetic Academy,
One of the clinical limitations to note is the heterogeneity in the quality of platelets
Cape Town, South Africa.
and blood components due to use of different PRF preparation protocols. Irrespective
E-mail: docg@mweb.co.za

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of the protocol used all studies have all reported successful (PRF) and Platelet concentrates up to May 2016. The search
outcomes with regards to soft and bone tissue healing and was complimented by an additional hand search of selected
regeneration. It should also be noted that at this stage in journals in oral implantology, oral surgery and periodontal,
time there is not a single RCT or CCT to compare the as well as grey literature. The reference lists and
effectiveness of A-PRF or L-PRF protocols. The clinical bibliographies of all included publications were also
effectiveness of different PRF preparation protocols in various screened for relevant studies. The search was limited to the
clinical settings remains to be validated through independent English language. Randomized controlled trials (RCTs),
robust RCTs. controlled clinical trials (CCTs), case reports, case series,
prospective, retrospective and in-vitro/in vivo studies were
Introduction included in the narrative review. Only RCTs, CCTs, and
The prospect of having new therapies, biomaterials and systematic reviews were used for evaluating evidence-based
bioactive surgical additives available that will improve data (Tables 1, 2, 3). Animal studies were excluded from
success and predictability of patient outcomes in soft and this review.
bone tissue healing and regeneration are key treatment
objectives in dental implantology, periodontology and oral Where and how can I use PRF?
surgery. A general rule of guidance is to use PRF in surgical situations
Platelet Rich Fibrin (PRF), a patient blood-derived and where protection and stimulation of healing and regeneration
autogenous living biomaterial, is increasingly being is critical and where the prognosis for tissue repair is poor
investigated and used worldwide by clinicians as an or potentially compromised in the absence of a tissue
adjunctive autologous biomaterial to promote bone and soft regeneration scaffold and addition of growth factors.
tissue healing and regeneration. The gold standard for in vivo
tissue healing and regeneration requires the mutual interaction Implant dentistry
between a scaffold (fibrin matrix), platelets, growth factors, Most of the PRF clinical research in implantology is currently
leukocytes, and stem cells.1 These key elements are all active focused in the fields of improving clinical outcomes with sinus
components of PRF, and when combined and prepared floor elevations using PRF as sole grafting material,
properly are involved in the key processes of tissue healing simultaneous with implant placement, 4,62 or SFE
and regeneration, including cell proliferation and using a combination of PRF and bone allograft (FDBA)
differentiation, extracellular matrix synthesis, chemotaxis and prior to implant placement.5,6 Other focus areas of clinical
angiogenesis (neo-vascularization).2,3 An improved implantology research are use of PRF in alveolar ridge
understanding of the development, biological and preservation (socket augmentation) 7, peri-implant tissue
physiological properties and characteristics of PRF in tissue healing 8, and improving implant stability. 9 (Table 1)
healing and regeneration over the last two decades, has led In-vitro studies have shown PRF-induced gene expression
to more successful therapeutic applications, especially in the of the early and late markers of osteogenesis, stimulates bone
fields of dental implantology, periodontology and oral surgery. and soft tissue healing.10 This finding suggests that PRF is
The purpose of this comprehensive review is to analyse the indicated in numerous clinical applications, such as, socket
available scientific literature on PRF regarding its: (Part I) (i) augmentation, jump gap filling during immediate extraction
definition and purpose in the clinical environment; (ii) and implant placement, and stimulation of bone and soft
development and classification of platelet concentrate tissue healing during bone augmentations or during sinus
biomaterials; (iii) biological characteristics and composition; elevation.
(Part II) (iv) preparation technique; (v) optimizing quality; (vi)
physical application and handling; and (vii) the benefits and Sinus floor elevation using PRF as sole or
limitations of PRF; and (Part III) (viii) its clinical indications in combination graft biomaterial
implant dentistry, periodontics, oral surgery and regenerative A systematic review showed that PRF used as a sole filling
endodontics. material in SFE with simultaneous implant placement is a
simple technique with promising results.4,11 Various clinical
Methodology, Search strategy and inclusion criteria case reports describe the lateral approach for sinus floor
An electronic MEDLINE (PubMed) and Google Scholar elevation using only PRF as the grafting material.12,13,14
search was performed for all articles on Platelet Rich Fibrin (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, Systematic PRF as a sole filling material for sinus lift with simultaneous implant
Abd-Elhakam, review placement is a simple technique with promising results. Addition
2016 4 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, RCT Use of PRF membranes to fill the socket after tooth extraction led
Gaydarov N, to improved alveolar bone healing and better preservation of the
Badoud I et al., alveolar crest width. These results support the use of a minimally
20137 traumatic procedure for tooth extraction and socket filling with
PRF to achieve preservation of hard tissue.

Peri-implant stability ncu E, CCT Results of this study demonstrated that PRF application into the
and healing Alaaddinoglu E, osteotomy site increases implant stability during the early healing
20159 period. Simple application of this material seems to provide faster
osseointegration.

Peri-implant tissue Boora P, Rathee PRF can be considered as a healing biomaterial with potential
healing M, Bhoria M. , RCT beneficial effect on peri-implant tissue and can be used as a
20158 therapeutic adjuvant in the clinical scenario of one stage, single
tooth implant placement procedure in maxillary anterior region.

Pre-implantology Choukroun J, Diss CCT Sinus floor augmentation with FDBA and PRF leads to a reduction
sinus floor elevation A, Simonpieri A, et of healing time prior to implant placement. From a histologic point
al (Part 5) 20065 of view, this healing time could be reduced to 4 months.

Pre-implantology Tatullo M, Marrelli CCT PRF together with deproteinized bovine bone (Bio-Oss) and
sinus elevation M, Cassetta M, et piezosurgery favors optimal bone regeneration compared to bone
al, 20126 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.
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 growth factors makes it an ideal replacement biomaterial to
and easily handled substitution biomaterial during sinus replace xenogenic and expensive collagen membranes in
elevation, to reduce the healing time before loading. It is a some situations.12
cheap and easily handled material with healing properties. The review also suggests that PRF combined with a bone
Its fibrin matrix properties and ability of slowly releasing allograft or other bone substitutes, accelerates graft

Figure 1a: PRF used as sole grafting Figure 1b: Multiple layers of PRF used for Figure 1c: Sinus osteotomy covered with
material in lateral window sinus floor sinus floor elevation. a collagen membrane.
elevation.

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Figure 2a: Lateral window osteotomy Figure 2b: Sinus floor elevated and
ready for sinus floor elevation. grafted with simultaneous implant placed

Figure 2c: Sinus floor grafted with Figure 2d: Lateral window sinus Figure 2e: PRF membrane (double layer)
xenograft mixed with PRF fragments. osteotomy covered with a collagen draped over the collagen membrane to
membrane. facilitate soft tissue wound healing.

maturation and decreases the healing period before implant therapeutic alternative for implant site preparation.24
placement.4 (Figure 2a 2e) The latter finding has also been Alternatively, PRF can also be mixed with a bone substitute
confirmed by other clinical trials and case studies. 5,6,15,16 to fill the socket, and used as a protective cover over the
Various case studies have demonstrated that PRF grafted socket. (Figure 4a - 4g) This is particularly important
membranes can be used successfully as a protective barrier when gingival wound closure is impossible or difficult with
to cover the sinus membrane during grafting procedures. the sutures.25 The purpose of the PRF membrane is to stimulate
4,6,12,17,18,19
(Figure 3) gingival healing, but also to protect the bone graft from the
PRF membranes also represent an easy and successful oral environment and to maintain it within the extraction
method to cover sinus membrane or osteotomy window to socket, like a biological barrier. It is suggested that this
protect the Schneiderian membrane, facilitate wound closure technique negates the need for using more complex flaps
and to enhance healing.4,12,17,20 and GBR protocols to close and augment extraction
Cases have also been reported showing that A-PRF sockets.25
membrane can be used as a healing barrier when
perforations or tears of the Schneiderian membrane
occur.17,18

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 Figure 3: PRF membrane used a protective barrier to cover the
that filling a fresh extraction socket with PRF provides a viable sinus membrane (Schneiderian membrane) before grafting.

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Figure 4a: Fresh extraction socket Figure 4b: PRF fragments placed into the Figure 4c: Bone putty alloplast injected
curetted and ready for augmentation. socket. into the socket.

Figure 4d: Plugger used to condense PRF Figure 4e: PRF plug placed on top of the Figure 4f: Socket closed with PRF plug
fragments and bone putty into the socket. bone putty. 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 leukocyte-platelet rich fibrin (L-PRF or A-PRF) membranes for
jump-gap augmentation Peri-implant healing the stimulation of bone and gingival healing around the
PRF can be considered as a healing biomaterial with implant is particularly significant.8,27 (Figure 6a - 6c) The
potential beneficial effect on peri-implant tissue and can be elastic consistency of the PRF membrane allows the clinician
used as a therapeutic adjuvant with immediate implant to punch a hole in the membrane to facilitate draping the
placement in the clinical scenario of one stage, single tooth membrane over the healing abutment. (Figure 7a & 7b)
implant placement procedure in maxillary anterior region.
8,119
With immediate implant placement the peri-implant Augmentation of dehiscence and fenestration defects
jump gap can be augmented with PRF clot (A-PRF or L-PRF) Case reports indicate that PRF membrane cut in pieces or
or solution (i-PRF) mixed with a bone substitute.26 (Figure 5a i-PRF combined with bone substitutes may offer an easy and
& 5b) In the latter case study it is suggested that the simple method of handling and delivery a fibrin scaffold,
augmented jump gap is covered with cross-linked collagen growth factors and cells during the augmentation of
membrane, overlayed by a double layer of PRF and the flap dehiscence and fenestration defects, and at the same time
closed by sutures. Studies have demonstrated that the use of 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 Figure 5b: Jump gap between implant and socket defect
placement. grafted with xenograft mixed with PRF fragments and covered
with a PRF membrane.

PRF has also been successfully used to treat fenestration PRF added to the maintenance of the graft homeostasis due
defects around implants.31 PRF membrane cut in pieces to release of growth factors, thus contributing to the successful
(Figure 8), or platelet liquid (I-PRF) (Figure 9) can be mixed outcome of treatment.33
with bone graft material to cover the defect. The graft is
covered with a resorbable collagen membrane to maintain Augmentation of alveolar ridges (horizontal and
form and shape and to confer graft stability and space vertical) and buccal bone defects (GBR)
maintenance on the bone particles. PRF membrane is then Several cases have been reported of successful
placed on top of the collagen membrane to prevent tissue augmentation of alveolar ridges where there is a buccal
dehiscence and aid in soft tissue healing. The application of bone defect (GBR) using PRF combined with a bone
PRF to GBR procedures offers several advantages including substitute,6,29, ,34,35,36,37,38,39 and in cases of the severely
promoting wound healing, bone growth and maturation, resorbed posterior mandible.40 The latter authors suggest that
graft stabilization, wound sealing and hemostasis and three layers of L-PRF membranes used alone were adequate
improving the handling properties of graft materials. to use as competitive interposition barrier to protect and
stimulate the bone compartment, and as healing membranes
Treatment of peri-implant osseous defects to stimulate the periosteum and gingival healing and
One clinical study showed that treatment of peri-implant remodeling. Periosteal incisions were done on the flaps to
defects with PRF was clinically more effective than with promote their tension-free closure.40 The concept of using PRF
conventional flap surgery alone, irrespective of the type of alone as a GBR barrier still raises many questions as well as
defect.32 In another study a successful treatment outcome was limitations and needs to be investigated with robust RCTs to
also reported after debridement and detoxification with a determine appropriate indications and relevant
Cr,CR:YCGG later, followed by filling the defect with a combinations. PRF liquid (i-PRF) can be injected, or PRF
30

synthetic hydroxyapatite embedded in native blood and membrane placed above the GBR or GTR membrane to act
covered with a PRF membrane to prevent soft tissue infiltration as a interposition barrier to protect and stimulate the bone
into the grafted area. The authors concluded that the use of compartment, and as a healing membrane in order to

Figure 6a: Implant site ready to be Figure 6b: PRF membrane draped around Figure 6c: Flap sutured.
draped with PRF membrane. an implant to stimulate bone and gingival
healing.

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Figure 7a: PRF membrane draped over the healing abutment Figure 7b: Flap closure over PRF membrane and around
to stimulate bone and gingival healing. healing abutment.

improve the soft tissue healing and remodeling, and thus overlaid with a double layer of PRF membranes. (Figure 10a
avoid soft tissue dehiscence.25,40 - 10c) These membranes were used as competitive
interposition barrier to protect and stimulate the bone
Guided bone regeneration compartment, and as healing membranes to stimulate the
Place harvested autogenous bone adjacent to the implant of periosteum and gingival healing and remodeling. Periosteal
defect that requires grafting. The next layer is made up of a releasing incisions are done on the flaps to promote their
mixture of bone grafting material with i-PRF or PRF membrane tension-free closure.40
or clot cut in small pieces. The objective of this mixture is to
help the rapid vascularization of the bone grafting material Increasing implant stability and osseointegration
through the PRF fibrin matrix making the bridge between Case studies suggest that PRF application into the
bone particles and allowing a quick new bone growth, while osteotomy site (Figure 11a -11c) increases implant stability
the xenograft material serves as space maintainer for the during the early healing period, as evidenced by higher ISQ
regenerative volume and supports the nucleation and values. Simple application of this material also seems to
accumulation of newly formed bone matrix. The bone/PRF provide faster osseointegration.9
mixture in the augmented site is covered with a cross-linked
collagen membrane to maintain the bone compartment and Periodontal surgery
to prevent ingrowth of soft tissue. The collagen membrane is Most of the clinical research in periodontology is currently

Figure 8: PRF membrane fragments mixed with bone particulate Figure 9: i-PRF mixed with bone particulate can be used
can be used successfully to augment alveolar ridge defects successfully to augment alveolar ridge defects using GBR
using GBR principles. principles.

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Table 2. Clinical evidence on the use of PRF in periodontology


Application Reference Type of Evidence / Conclusion
Study
The addition of autologous platelet concentrate (PRP and PRF) to open flap
Furcation defects Troiano G, Laino L, Meta-analysis debridement (OFD) may improve clinical parameters: horizontal and
Dioguardi M, et al, vertical clinical attachment level, probing depth and level of gingival margin
2016 15 in the treatment of mandibular class II furcation defects compared to OFD
alone.

Furcation defects Sharma et al. 2011b 45


RCT Significant improvement with PRF implies its role as a regenerative material
in treatment of furcation defects.

The results suggest that the use of PRF membranes did not improve the root
Recession defects Moraschini V,
coverage, keratinized mucosa width, or clinical attachment level of Miller
dos Santos E, Barboza Meta- analysis
class-I and -II gingival recessions compared to the other treatment
P., 2015 66
modalities.
Keceli HG, Kamak G, The addition of PRF did not further develop the outcomes of coronally
Recession defects Erdemir EO, RCT advance flap combined with a connective tissue graft treatment except
et al. , 2015 67 increasing the tissue thickness.
Recession defects Rajaram V, Thyegarajan R, RCT The additional application of PRF failed to improve root coverage after
Balachandran A, et al, double lateral sliding bridge flap in Millers Class I and II defects.
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
Bharwani A, , 2014 41
reduction, and reduction in probing depth when IBDs were treated with PRF
alone when compared to OFD.

PRF and PRGF platelet concentrate failed to augment the clinical effects
Intrabony defects Gamal AY, Ghaffar RCT achieved with the xenograft alone in treating intrabony defects. Periodontal
KAA, Alghezwy OA., defects could not retain extra-physiologic levels of GF suggested to be
2016 42 associated with platelet concentrate.

Shah M, Patel J, Dave PRF has shown significant results after 6 months, which are comparable to
Intrabony defects D, Shah S , 2015 43 RCT DFDBA for periodontal regeneration in terms of clinical parameters. PRF has
several advantages when used as a graft material for infrabony defects.

Sharma et al. 2011a44 Greater pocket depth reduction and periodontal attachment level (PAL) gain,
Intrabony defects RCT and bone fill at sites treated with PRF combined with conventional open-flap
debridement compared to conventional open-flap debridement alone.

The use of autologous PRF or PRP was effective in the treatment of 3-wall
Pradeep AR, Rao NS, IBDs with uneventful healing of sites. Treatment with autologous PRF or PRP
Agarwal P, et al, 2012 RCT stimulated a significant increase in the PD reduction, GML, and bone fill
Intrabony defects 46
compared with OFD at 9 months.

PRF combined with demineralized-freeze dried bone allograft (DFDBA)


Intrabony defects Bansal C and Bharti V, CCT demonstrated better results in probing pocket depth reduction and clinical
2013 47 attachment level gain as compared to DFDBA alone in the treatment of
periodontal intrabony defects.
Intrabony defects RCT
Thorat MK, Pradeep Greater reduction in pocket depth, more clinical attachment level gain and
AR, Pallavi B., 2011 48
greater intra-bony defect fill at sites treated with PRF compared to open flap
debridement alone.
Intrabony defects
Pradeep AR, Bajaj P, PRF when added to porous hydroxyapatite (HA) increases the regenerative
Rao NS, et al 2012 49 RCT
effects observed with PRF in treatment of human three-wall intra-bony
defects.

Femminella B, Iaconi MC, The PRF-enriched palatal bandage significantly accelerates palatal wound
Palatal bandage RCT
Di Tullio M, 2016. 76 healing and reduces the patients morbidity.

Within the limitations of the studies, and more and large samples rigorous clinical trials are required to validate the evidence.

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Figure 10a: Using PRF fragments mixed Figure 10b: Bone graft covered with Figure 10c: Bone graft and collagen
with autogenous bone to fill spaces in collagen membrane. membrane covered with multiple PRF
guided bone regeneration procedure. membranes.

focused in the fields of improving clinical outcomes with induction of a strong and thick periosteum and gingiva. The
treatment of intra-bony periodontal pockets, furcation defects, boosted periosteum functions as a true barrier between the
gingival recession defects, and healing of connective tissue soft tissue and bone compartments, and constitutes probably
graft sites in the palate. (Table 2) the best protection and regenerative barrier for the intrabony
defects.25 The NTR protocol25 is very simple and gives
Intrabony and furcation periodontal defects excellent results in most clinical situations, with no
The regenerative and wound healing effects have been very contraindication or risk of negative effects. However, in order
promising with PRF treating intrabony defects, to get the best results, the choice and the quantity of the
41,42,43,44,45,46,47,48,49,50,51
(Table 3) The abovementioned adequate bone substitute has yet to be determine in various
clinical evidence is supported by several case studies clinical configurations.
reporting on the successful application of PRF to regenerate Theoretically, PRF can be used as a sole grafting material
bone and gingival tissues around teeth presenting with or in combination with bone substitutes can be used as a
intrabony defects, 41,44,46,47,48,49,52,53,54,55,56,66 and furcation filling material in intrabony defects, following GTR
lesions.45,57,58,59,60,61 principles.12,119
Another study has also reported on using PRF successfully PRF membrane is a solid material with the advantage that
as a regenerative material in cases of aggressive it is easy to handle and to position in bony defects. PRF
periodontitis.60 membranes can also be used as a protection membrane
Surgical periodontal therapy accompanying the placement after the filling of the intrabony defect. (Figure 12a & 12b)
of PRF in angular defects of aggressive periodontitis patients In comparison to GTR membranes, PRF will undergo a
showed decreased probing pocket depth, increased quicker remodeling in situ than a resorbable collagen
attachment level and radiographic bone fill when baseline membrane, but will promote a strong induction on the
and 9 month follow-up data was compared. Surgical periosteum and gingival tissue due to the slow release of
reconstructive therapy with placement of PRF in angular growth factors and other matrix proteins.63,64,65
defects can is suggested as an effective approach to GTR membranes are cell-proof barriers, whereas a PRF
enhance periodontal regeneration.60 membrane is a highly stimulating matrix, attracting cell
Platelet gel acts as a stabilized blood clot and therefore migration and preferential differentiation allowing new blood
recommended as a perfect filling material for natural tissue vessel formation within the matrix, and also reinforcing the
regeneration and healing.25 Clinically, the general concept natural periosteal barrier. The hard and soft tissues migrate
of Natural Tissue Regeneration (NTR) and Natural Bone and interact within the PRF matrix. The PRF matrix becomes
Regeneration (NBR)25 requires to fill the periodontal intrabony the interface between the tissues and therefore avoids the
defect with L-PRF, most times in association with a bone migration of the soft tissues deeper within the grafted defect
substitute used as a solid space maintainer, and then to cover or augmented site. This biological characteristic is referred
the filled intrabony defect with L-PRF membranes, used for the to as a competitive barrier.64
protection of the grafted area and as a healing booster for These bioactive interactions are very important during
the soft tissues above the defects.25 The objective of this cover tissue regeneration, since the periosteum covers the internal
is not only to protect the blood clot and/or the filling part of the gingival flap and is a key actor of bone healing
material, like in the GTR concept, but also to promote the 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 Figure 11b: Implant wetted with PRF exudate containing growth
PRF membrane factors.

periosteum healing potential and bone/gingival interactions, Palatal bandage


PRF membranes stimulate the periosteums regenerative PRF membranes can also be used as a palatal wound
properties. However, even if PRF membranes do not block bandage or protection membranes after harvesting
the migration of the cells, no invagination of the soft tissues connective tissue grafts in the palate.76,77,78 Case studies
within the bone area were observed when PRF membranes show that PRF membrane used as a palatal bandage is an
covered a filled intrabony defect.62 efficacious approach to protect the raw wound area of a
palatal donor site and significantly accelerates palatal
Recession defects and guided tissue regeneration (GTR) wound healing and reduces patient discomfort and healing
The clinical evidence is less promising with the treatment time.78,79,80
of recession defects.66,67,68 (Table 2) Within the limitations of
available clinical trials, the clinical evidence indicate that PRF Inter-dental papilla augmentation
does not improve root coverage or increases the width of A case study reported that PRF combined with bone graft for
keratinized mucosa in Millers Class I and II gingival regeneration of interdental bone may contribute towards
recessions, compared to other treatment modalities. improved clinical success with
However, cases have been reported where PRF was augmentation of lost dental papilla.81 The reconstructed
successfully used for treating localized, 64,69,70,71,72,73 and papilla in the new position was stable when reviewed at 3
multiple74 gingival recessions. Another case study reported and 6 months postoperatively.
that the use of PRF membrane along with the VISTA technique
allows clinicians to successfully treat multiple recession Oral Surgery
defects with optimal esthetic results and excellent soft tissue Most of the evidence-based research in the field of oral
biotype.75

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Figure 12a: Intrabony defect after root planning and soft laser Figure 12b: Closure of flap over the grafted intrabony defect.
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.

surgery is primarily focused on enhancing bone healing medication presenting a risk of osteonecrosis of the jaws, or
82,83,84
and reducing postoperative complications following patients receiving anticoagulants.93
3rd molar extractions. 82,85,86 (Table 3) Research is also Delayed or compromised healing of extraction sockets is
emerging on promoting healing of apico-marginal defects in mostly related to an unstable blood clot within the socket. In
root end surgery. (Table 3) Numerous case and case series such case a fibrin clot is simply placed in the socket, covered
studies have been reported that support the use of PRF in with a collagen plug or membrane and sutured. Placing PRF
various clinical applications in the field of oral surgery. 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 Prevention of periodontal complications in 3rd molar
highly dependent on the initial stabilization of the blood clot surgery
and the quick gingival wound closure. This can be achieved Complex third molar extractions frequently result in critical
by placing fibrin plug in the socket (with or without a bone size bone defects and compromised healing impacting
substitute) and closing with a fibrin membrane. The use of negatively on the outcome of periodontal tissues distal of the
PRF as a post extraction sockets filling biomaterial is second molar. When bone defects after extraction are
recommended as a useful procedure in order to reduce the critical-sized (and often associated with cystic lesions), Using
early adverse effects of the inflammation, such as PRF as a filling material or mixing PRF with a bone substitute
postoperative pain,82,85,86 and to promote the soft tissue in order to use a significant volume of solid biomaterial for
healing and bone regeneration process.87 filling is considered as reliable option. These treatments are
Clinical situations where post-extraction socket however no more simple dental extractions, and are often at
augmentation with PRF is specifically indicated are for early the border of guided bone regeneration (GBR) or bone
or delayed implant placement; and immediate post-extraction grafting. The use of a PRF as a filling material significantly
implant placement.7,20 ,21,24,26,83,88,89,90,91,92 promotes soft tissue healing and also faster
regeneration of bone in these sites and neighboring
Reduce post-extraction complications in medically periodontal tissues.84,94,95
compromised cases
PRF can be used to minimize post-extraction complications Closing oro-antral fistulas
such as, osteitis, dry or infected sockets resulting from and Oro-antral communications can complicate dental surgery,
delayed or potentially compromised healing or bleeding particularly during extraction of a posterior maxillary root.
situations in systemic conditions such as such as with PRF clots can be used successfully for atraumatic or minimal
diabetics; patients receiving on oral bisphosphonate intervention closure of oro-antral communications, thus

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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 Reference RCT PRF application may decrease the risk of alveolar osteitis
complications in Eshghpour et al, development after mandibular third molar surgery.
3rd molar 201485
extractions

Enhance bone Gurbuzer B, CCT PRF might not lead to enhanced bone healing in soft tissue
healing after 3rd Pikdken L, Tunal impacted mandibular third molar extraction sockets 4 weeks
molar extractions M, et al, 201083 after surgery.

Bone regeneration Rao SG, Bhat P, CCT PRF accelerate regeneration of bone after third molar
after 3rd molar K. S. Nagesh KS, extraction surgery in cases treated with PRF as compared to
extractions et al, 2013 84 the control group post operatively.

Bone healing and Singh A, Kohli M, PRF is a valid method in promoting and accelerating soft and
post-operative Gupta N, 201282 CCT hard tissue wound healing and regeneration, and decreasing
complications after pain in mandibular 3rd molar extractions.
3rd molar surgery

Post-operative Uyank LO, PRF and combination use of PRF and piezosurgery have
complications Bilginaylar K, CCT positive effects in reducing postoperative complications (pain
following 3rd molar Etikan I., 201586 and trismus) after impacted third molar surgery.
extractions

Root-end surgery / Dhiman M, Kumar RCT A high success rate may be attained in apico-marginal defects
Healing of S, Duhan J, et al with endodontic microsurgery, and addition of PRF may not
apico-marginal 2015.102 necessarily improve the outcome.
defects

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 Other oral surgical applications where PRF is used
flaps.96 The technique for closure of an oro-antral fistula using Alveolar cleft grafting
platelet-rich fibrin is described by Argawal and co-workers.97 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 Bisphosphonate related oral necrosis of the jaw
surgical procedures to enhance soft tissue healing and bone Recent case reports suggested that PRF might stimulate
regeneration. 98,99,100,101 Other researchers report that PRF gingival healing and act as a barrier membrane between
may not necessarily improve the outcome of treatment. 102 alveolar bone and the oral cavity, therefore offering a simple,
The combination of PRF membrane as a matrix and MTA can though effective treatment for the closure of bone exposure
prove to be an effective alternative for creating artificial root- in BRONJ. 107,108,109,120
end barriers and to induce faster peri-apical healing with

combination of PRF and -TCP for bone augmentation in


large periapical lesions.103 It is suggested that the
Compromised wound healing situations (Diabetics)
PRF has also been used as an adjuvant in the
treatment of periapical defects is also a more effective at management of problematic chronic wounds.109 The
increasing healing time compared to using bone substitute authors have shown that growth factors in PRF are
material alone.104 PRF combined with an alloplastic bone protected from proteolytic degradation. This may be
substitute has been successfully used for the management of advantageous in the treatment of chronic wounds
combined endodontic-periodontal lesions.105 characterized by high proteinase activity.

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Regenerative endodontic therapy scaffold (fibrin matrix), platelets, growth factors, leukocytes,
Regenerative endodontic procedures are widely being added and stem cells. These key elements are all active components
to the current armamentarium of pulp therapy of PRF in whichever form, and when combined and prepared
procedures.105,110,111,112,113,114 properly are involved in the key processes of tissue healing
These biologically based procedures are designed to and regeneration, whilst at the same time reducing adverse
restore function of a damaged and non-functioning pulp by events. Clinicians are using PRF is extensively and successfully
stimulation of existing dental pulp stem and progenitor cells in various clinical applications in dental implantology,
present in the root canal under conditions that are favorable periodontology, maxillofacial and oral surgery, and lately in
to their differentiation.110,111 regenerative endodontics, to promote wound healing and
tissue regeneration. The use of PRF in revitalization,
Management of open apex revascularization, and regenerative pulp therapies are
Recent case reports have shown that the combined use of currently attracting a lot of attention and several case studies
platelet-rich fibrin (PRF), and mineral trioxide aggregate (MTA) in the field of regenerative endodontics are being reported.
as root filling material is beneficial for the endodontic These applications however still need to be validated with
management of an open apex. 112,115,116 robust clinical trials.
It is hypothesized that the combination of MTA and PRF may One of the clinical limitations to note is the heterogeneity
have a synergistic effect on the stimulation of odontoblastic in the quality of platelets and blood components due to use
differentiation of stem cells. of different PRF preparation protocols in the various studies
reviewed. Irrespective of the protocol used all studies have
Revascularization and revitalization all reported successful outcomes with regards to soft and bone
Revascularization is the most studied and successful tissue healing and regeneration. It should also be noted that
approach of regenerative endodontics.115 Revitalization of at this stage in time there is not a single RCT or CCT to
necrotic infected immature tooth is possible under conditions compare the effectiveness of A-PRF or L-PRF protocols.
of total canal disinfection combined with the additive effect Furthermore, in vitro studies that claim superiority or inferiority
of PRF. 117,118 PRF is proposed as an ideal biomaterial for pulp- of a specific PRF preparation have yet to be validated by
dentin complex regeneration because it is a potentially valid independent clinical trials. The future of PRF and it
scaffold material containing leukocyte and growth factors to applications in clinical dentistry, especially in the field of soft
facilitate tissue healing and regeneration in immature necrotic tissue and bone regeneration has enormous implications, but
teeth in children. 115,116,117 developing and strengthening its role in dentistry is dependent
Repair and regenerative potential of PRF, and enhanced on its coherence and scientific clarity. The clinical
cellular metabolism with laser bio stimulation, in combination effectiveness of different PRF preparation protocols in various
with the sealing ability of MTA enhances the clinical success clinical settings remains to be validated with a greater number
outcomes in pulpotomy and apexification procedures.115 of independent and robust RCTs, preferably with a split mouth
Revitalization, revascularization, and regenerative pulp design, and larger sample sizes. Independent, coherent and
therapies still needs to be validated with robust clinical trials. scientific validation of PRF is needed to enhance the potential
of this technology, thereby extending its therapeutic
Conclusion applications with improved successful and predictable
PRF is increasingly being investigated and used by clinicians outcomes for the benefit of the patient. PRF technology is in
worldwide as an adjunctive autologous biomaterial to its infancy and will in future have a big impact in dentistry.
promote bone and soft tissue healing and regeneration. PRF The benefits derived from the using PRF in various clinical
has also grabbed the attention of clinicians because this applications for promoting wound healing and tissue
biomaterial is derived from the patients own blood; is easy regeneration, its antibacterial and anti-haemorrhagic effects, the
to make at chair-side, easy to use within the daily clinical low risks with its use, and the availability of easy and low cost
routine; widely applicable in dentistry with virtually no risk of preparation methods, should encourage more clinicians to adopt
rejection; whilst being financially realistic for the patient and this technology in their practice for the benefit their patients.
the practice. The 3D architecture of the fibrin matrix provides
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