A comprehensive clinical review of Platelet Rich Fibrin ... · PDF file64 INTERNATIONAL DENTISTRY – AFRICAN EDITION VOL. 6, NO. 5 A comprehensive clinical review of Platelet Rich

64 INTERNATIONAL DENTISTRY – AFRICAN EDITION VOL. 6, NO. 5

A comprehensive clinical review of Platelet Rich Fibrin(PRF) and its role in promoting tissue healing andregeneration in dentistry. Part III: Clinical indications ofPRF in implant dentistry, periodontology, oral surgeryand regenerative endodontics

Johan Hartshorne1 and Howard Gluckman2

SummaryThe 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 understandingof the clinical indications of PRF will facilitate the clinicians’ ability to enhance thetherapeutic applications of PRF in these fields. PRF is increasingly being investigatedand used world-wide by clinicians as an adjunctive autologous biomaterial to promotebone and soft tissue healing and regeneration. PRF has also grabbed the attention ofclinicians 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; widelyapplicable in dentistry with virtually no risk of rejection; whilst being financially realisticfor the patient and the practice. The 3D architecture of the fibrin matrix provides thePRF membrane with great density, elasticity, flexibility and strength that are excellentlysuited for handling, manipulation and suturing. The gold standard for in vivo tissuehealing and regeneration requires the mutual interaction between a scaffold (fibrinmatrix), platelets, growth factors, leukocytes, and stem cells. These key elements are allactive components of PRF, and when combined and prepared properly, in whicheverform, are involved in the key processes of tissue healing and regeneration. PRF iswidely being used with promising results in various clinical applications with the primaryaim of promoting wound healing, accelerating graft maturation, decreasing the healingperiod, protecting and promoting improved outcomes in soft tissue and bone healing,and tissue regeneration. PRF combined with GBR procedures offers several added andsynergistic advantages including promoting wound healing in compromised woundhealing situations, bone growth and maturation, graft stabilization, wound sealing andhemostasis, and improving the handling properties of graft materials. PRF added to, orcombined with bone substitutes, offer an effective and easy way for managing and/oraugmenting peri-implant osseous defects, sinus floor elevations, intrabony defects, freshextraction sockets and alveolar ridges with deficient or atrophied alveolar bone. PRFmembranes used as a protective or wound bandage on connective tissue harvestingsites (palate) or donor sites (vestibule), significantly accelerates wound healing andreduces post-operative pain and discomfort. The use of PRF in revitalization,revascularization, and regenerative pulp therapies are currently attracting a lot ofattention and several case studies in the field of regenerative endodontics are beingreported.

One of the clinical limitations to note is the heterogeneity in the quality of plateletsand blood components due to use of different PRF preparation protocols. Irrespective

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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 DentalCentre, Tyger Valley, Bellville,7530. South Africa. E-mail:[email protected]

2 Howard Gluckman BDS.,M.Ch.D. (OMP) (Wits) SpecialistIn Periodontics and OralMedicine, Director of The Implantand Aesthetic Academy, Cape Town, South Africa.E-mail: [email protected]

VOL. 6, NO. 5 INTERNATIONAL DENTISTRY – AFRICAN EDITION 65

(PRF) and Platelet concentrates up to May 2016. The searchwas complimented by an additional hand search of selectedjournals in oral implantology, oral surgery and periodontal,as well as grey literature. The reference lists andbibliographies of all included publications were alsoscreened for relevant studies. The search was limited to theEnglish language. Randomized controlled trials (RCT’s),controlled clinical trials (CCT’s), case reports, case series,prospective, retrospective and in-vitro/in vivo studies wereincluded in the narrative review. Only RCT’s, CCT’s, andsystematic reviews were used for evaluating evidence-baseddata (Tables 1, 2, 3). Animal studies were excluded fromthis review.

Where and how can I use PRF? A general rule of guidance is to use PRF in surgical situationswhere protection and stimulation of healing and regenerationis critical and where the prognosis for tissue repair is pooror potentially compromised in the absence of a tissueregeneration scaffold and addition of growth factors.

Implant dentistryMost of the PRF clinical research in implantology is currentlyfocused in the fields of improving clinical outcomes with sinusfloor 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 clinicalimplantology research are use of PRF in alveolar ridgepreservation (socket augmentation) 7, peri-implant tissuehealing 8, and improving implant stability. 9 (Table 1)

In-vitro studies have shown PRF-induced gene expressionof the early and late markers of osteogenesis, stimulates boneand soft tissue healing.10 This finding suggests that PRF isindicated in numerous clinical applications, such as, socketaugmentation, jump gap filling during immediate extractionand implant placement, and stimulation of bone and softtissue healing during bone augmentations or during sinuselevation.

• Sinus floor elevation using PRF as sole orcombination graft biomaterial

A systematic review showed that PRF used as a sole fillingmaterial in SFE with simultaneous implant placement is asimple technique with promising results.4,11 Various clinicalcase reports describe the lateral approach for sinus floorelevation using only PRF as the grafting material.12,13,14

(Figure 1a, 1b & 1c)

of the protocol used all studies have all reported successfuloutcomes with regards to soft and bone tissue healing andregeneration. It should also be noted that at this stage intime there is not a single RCT or CCT to compare theeffectiveness of A-PRF or L-PRF protocols. The clinicaleffectiveness of different PRF preparation protocols in variousclinical settings remains to be validated through independentrobust RCT’s.

IntroductionThe prospect of having new therapies, biomaterials andbioactive surgical additives available that will improvesuccess and predictability of patient outcomes in soft andbone tissue healing and regeneration are key treatmentobjectives in dental implantology, periodontology and oralsurgery.

Platelet Rich Fibrin (PRF), a patient blood-derived andautogenous living biomaterial, is increasingly beinginvestigated and used worldwide by clinicians as anadjunctive autologous biomaterial to promote bone and softtissue healing and regeneration. The gold standard for in vivotissue healing and regeneration requires the mutual interactionbetween a scaffold (fibrin matrix), platelets, growth factors,leukocytes, and stem cells.1 These key elements are all activecomponents of PRF, and when combined and preparedproperly are involved in the key processes of tissue healingand regeneration, including cell proliferation anddifferentiation, extracellular matrix synthesis, chemotaxis andangiogenesis (neo-vascularization).2,3 An improvedunderstanding of the development, biological andphysiological properties and characteristics of PRF in tissuehealing and regeneration over the last two decades, has ledto more successful therapeutic applications, especially in thefields of dental implantology, periodontology and oral surgery.

The purpose of this comprehensive review is to analyse theavailable scientific literature on PRF regarding its: (Part I) (i)definition and purpose in the clinical environment; (ii)development and classification of platelet concentratebiomaterials; (iii) biological characteristics and composition;(Part II) (iv) preparation technique; (v) optimizing quality; (vi)physical application and handling; and (vii) the benefits andlimitations of PRF; and (Part III) (viii) its clinical indications inimplant dentistry, periodontics, oral surgery and regenerativeendodontics.

Methodology, Search strategy and inclusion criteriaAn electronic MEDLINE (PubMed) and Google Scholarsearch was performed for all articles on Platelet Rich Fibrin

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growth factors makes it an ideal replacement biomaterial toreplace xenogenic and expensive collagen membranes insome situations.12

The review also suggests that PRF combined with a boneallograft or other bone substitutes, accelerates graft

The PRF membrane is recommended as an inexpensiveand easily handled substitution biomaterial during sinuselevation, to reduce the healing time before loading. It is acheap and easily handled material with healing properties.

Its fibrin matrix properties and ability of slowly releasing

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Application Reference Type of Study Evidence / Conclusion†

Sinus floor elevation

Socket Augmentation

Peri-implant stabilityand healing

Peri-implant tissuehealing

Pre-implantologysinus floor elevation

Pre-implantologysinus elevation

Ali S, Bakry SA,Abd-Elhakam,2016 4

Hauser F,Gaydarov N,Badoud I et al.,20137

Öncu E,Alaaddinoõglu E,20159

Boora P, RatheeM, Bhoria M. ,20158

Choukroun J, DissA, Simonpieri A, etal (Part 5) 20065

Tatullo M, MarrelliM, Cassetta M, etal, 20126

Systematicreview

RCT

CCT

RCT

CCT

CCT

PRF as a sole filling material for sinus lift with simultaneous implantplacement is a simple technique with promising results. Additionof PRF to DFDBA accelerates graft maturation and decreases thehealing period before implant placement. PRF membranesrepresent an easy and successful method to cover sinusmembrane or osteotomy window.

Use of PRF membranes to fill the socket after tooth extraction ledto improved alveolar bone healing and better preservation of thealveolar crest width. These results support the use of a minimallytraumatic procedure for tooth extraction and socket filling with PRF to achieve preservation of hard tissue.

Results of this study demonstrated that PRF application into theosteotomy site increases implant stability during the early healingperiod. Simple application of this material seems to provide fasterosseointegration.

PRF can be considered as a healing biomaterial with potentialbeneficial effect on peri-implant tissue and can be used as atherapeutic adjuvant in the clinical scenario of one stage, singletooth implant placement procedure in maxillary anterior region.

Sinus floor augmentation with FDBA and PRF leads to a reductionof healing time prior to implant placement. From a histologic pointof view, this healing time could be reduced to 4 months.

PRF together with deproteinized bovine bone (Bio-Oss) andpiezosurgery favors optimal bone regeneration compared to bonegraft material alone. At 106 days, it is already possible to achievegood primary stability of endosseous implants, though lacking offunctional loading. PRF favors clot stability and the membranousshape allows creating a natural “barrier effect” on the bonebreaches that were opened in the surgical areas.

Table 1. Evidence-based literature on the use of PRF in implant dentistry

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

Figure 1a: PRF used as sole graftingmaterial in lateral window sinus floorelevation.

Figure 1b: Multiple layers of PRF used forsinus floor elevation.

Figure 1c: Sinus osteotomy covered witha collagen membrane.

therapeutic alternative for implant site preparation.24

Alternatively, PRF can also be mixed with a bone substituteto fill the socket, and used as a protective cover over thegrafted socket. (Figure 4a - 4g) This is particularly importantwhen gingival wound closure is impossible or difficult withthe sutures.25 The purpose of the PRF membrane is to stimulategingival healing, but also to protect the bone graft from theoral environment and to maintain it within the extractionsocket, like a biological barrier. It is suggested that thistechnique negates the need for using more complex flapsand GBR protocols to close and augment extractionsockets.25

maturation and decreases the healing period before implantplacement.4 (Figure 2a – 2e) The latter finding has also beenconfirmed by other clinical trials and case studies. 5,6,15,16

Various case studies have demonstrated that PRFmembranes can be used successfully as a protective barrierto cover the sinus membrane during grafting procedures.4,6,12,17,18,19 (Figure 3)

PRF membranes also represent an easy and successfulmethod to cover sinus membrane or osteotomy window toprotect the Schneiderian membrane, facilitate wound closureand to enhance healing.4,12,17,20

Cases have also been reported showing that A-PRFmembrane can be used as a healing barrier whenperforations or tears of the Schneiderian membraneoccur.17,18

• Alveolar ridge preservation (socket augmentation)for early or late implant placement

Use of PRF membranes to fill the socket after toothextraction has shown to improve alveolar bone healing andpreservation of the alveolar crest width.7 PRF plugs ormembranes can also be used to fill extraction sockets, evenwhen associated with compromised extraction sockets21,severe cystic destructions or after cyst enucleations,22,20,23 toallow early bone and gingival regeneration required forimplant placement. Clinical and histological findings suggestthat filling a fresh extraction socket with PRF provides a viable

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Figure 2a: Lateral window osteotomyready for sinus floor elevation.

Figure 2b: Sinus floor elevated andgrafted with simultaneous implant placed

Figure 2c: Sinus floor grafted withxenograft mixed with PRF fragments.

Figure 2d: Lateral window sinusosteotomy covered with a collagenmembrane.

Figure 2e: PRF membrane (double layer)draped over the collagen membrane tofacilitate soft tissue wound healing.

Figure 3: PRF membrane used a protective barrier to cover thesinus membrane (Schneiderian membrane) before grafting.

leukocyte-platelet rich fibrin (L-PRF or A-PRF) membranes forthe stimulation of bone and gingival healing around theimplant is particularly significant.8,27 (Figure 6a - 6c) Theelastic consistency of the PRF membrane allows the clinicianto punch a hole in the membrane to facilitate draping themembrane 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 andsimple method of handling and delivery a fibrin scaffold,growth factors and cells during the augmentation ofdehiscence and fenestration defects, and at the same timereduce soft tissue and bone healing time.20,28,29, 30

• Immediate postextraction implant placement andjump-gap augmentation – Peri-implant healing

PRF can be considered as a healing biomaterial withpotential beneficial effect on peri-implant tissue and can beused as a therapeutic adjuvant with immediate implantplacement in the clinical scenario of one stage, single toothimplant placement procedure in maxillary anterior region.8,119 With immediate implant placement the peri-implantjump 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 theaugmented jump gap is covered with cross-linked collagenmembrane, overlayed by a double layer of PRF and the flapclosed by sutures. Studies have demonstrated that the use of

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Figure 4a: Fresh extraction socketcuretted and ready for augmentation.

Figure 4b: PRF fragments placed into thesocket.

Figure 4c: Bone putty alloplast injectedinto the socket.

Figure 4d: Plugger used to condense PRFfragments and bone putty into the socket.

Figure 4e: PRF plug placed on top of thebone putty.

Figure 4f: Socket closed with PRF plugand used as a protective cover over thegrafted socket.

Figure 4g: Provisional removable prosthesis with ovate pontic seated over thegrafted socket.

PRF added to the maintenance of the graft homeostasis dueto release of growth factors, thus contributing to the successfuloutcome of treatment.33

• Augmentation of alveolar ridges (horizontal andvertical) and buccal bone defects (GBR)

Several cases have been reported of successfulaugmentation of alveolar ridges where there is a buccalbone defect (GBR) using PRF combined with a bonesubstitute,6,29, ,34,35,36,37,38,39 and in cases of the severelyresorbed posterior mandible.40 The latter authors suggest thatthree layers of L-PRF membranes used alone were adequateto use as competitive interposition barrier to protect andstimulate the bone compartment, and as healing membranesto stimulate the periosteum and gingival healing andremodeling. Periosteal incisions were done on the flaps topromote their tension-free closure.40 The concept of using PRFalone as a GBR barrier still raises many questions as well aslimitations and needs to be investigated with robust RCT’s todetermine appropriate indications and relevantcombinations.30 PRF liquid (i-PRF) can be injected, or PRFmembrane placed above the GBR or GTR membrane to actas a interposition barrier to protect and stimulate the bonecompartment, and as a healing membrane in order to

PRF has also been successfully used to treat fenestrationdefects around implants.31 PRF membrane cut in pieces(Figure 8), or platelet liquid (I-PRF) (Figure 9) can be mixedwith bone graft material to cover the defect. The graft iscovered with a resorbable collagen membrane to maintainform and shape and to confer graft stability and spacemaintenance on the bone particles. PRF membrane is thenplaced on top of the collagen membrane to prevent tissuedehiscence and aid in soft tissue healing. The application ofPRF to GBR procedures offers several advantages includingpromoting wound healing, bone growth and maturation,graft stabilization, wound sealing and hemostasis andimproving the handling properties of graft materials.

Treatment of peri-implant osseous defects One clinical study showed that treatment of peri-implantdefects with PRF was clinically more effective than withconventional flap surgery alone, irrespective of the type ofdefect.32 In another study a successful treatment outcome wasalso reported after debridement and detoxification with aCr,CR:YCGG later, followed by filling the defect with asynthetic hydroxyapatite embedded in native blood andcovered with a PRF membrane to prevent soft tissue infiltrationinto the grafted area. The authors concluded that the use of

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Figure 5a: Residual root to be extracted for immediate implantplacement.

Figure 5b: Jump gap between implant and socket defectgrafted with xenograft mixed with PRF fragments and coveredwith a PRF membrane.

Figure 6a: Implant site ready to bedraped with PRF membrane.

Figure 6b: PRF membrane draped aroundan implant to stimulate bone and gingivalhealing.

Figure 6c: Flap sutured.

overlaid with a double layer of PRF membranes. (Figure 10a- 10c) These membranes were used as competitiveinterposition barrier to protect and stimulate the bonecompartment, and as healing membranes to stimulate theperiosteum and gingival healing and remodeling. Periostealreleasing incisions are done on the flaps to promote theirtension-free closure.40

• Increasing implant stability and osseointegrationCase studies suggest that PRF application into the

osteotomy site (Figure 11a -11c) increases implant stabilityduring the early healing period, as evidenced by higher ISQvalues. Simple application of this material also seems toprovide faster osseointegration.9

Periodontal surgeryMost of the clinical research in periodontology is currently

improve the soft tissue healing and remodeling, and thusavoid soft tissue dehiscence.25,40

Guided bone regenerationPlace harvested autogenous bone adjacent to the implant ofdefect that requires grafting. The next layer is made up of amixture of bone grafting material with i-PRF or PRF membraneor clot cut in small pieces. The objective of this mixture is tohelp the rapid vascularization of the bone grafting materialthrough the PRF fibrin matrix making the bridge betweenbone particles and allowing a quick new bone growth, whilethe xenograft material serves as space maintainer for theregenerative volume and supports the nucleation andaccumulation of newly formed bone matrix. The bone/PRFmixture in the augmented site is covered with a cross-linkedcollagen membrane to maintain the bone compartment andto prevent ingrowth of soft tissue. The collagen membrane is

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Figure 7a: PRF membrane draped over the healing abutmentto stimulate bone and gingival healing.

Figure 7b: Flap closure over PRF membrane and aroundhealing abutment.

Figure 8: PRF membrane fragments mixed with bone particulatecan be used successfully to augment alveolar ridge defectsusing GBR principles.

Figure 9: i-PRF mixed with bone particulate can be usedsuccessfully to augment alveolar ridge defects using GBRprinciples.

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Application Reference Type of Evidence / Conclusion† Study

Furcation defects

Furcation defects

Recession defects

Recession defects

Recession defects

Intrabony defects

Intrabony defects

Intrabony defects

Intrabony defects

Intrabony defects

Intrabony defects

Intrabony defects

Intrabony defects

Palatal bandage

Troiano G, Laino L,Dioguardi M, et al,2016 15

Sharma et al. 2011b 45

Moraschini V, dos Santos E, BarbozaP., 2015 66

Keceli HG, Kamak G,Erdemir EO, et al. , 2015 67

Rajaram V, Thyegarajan R,Balachandran A, et al,2015 68

Shah M, Deshpande N,Bharwani A, , 2014 41

Gamal AY, GhaffarKAA, Alghezwy OA.,2016 42

Shah M, Patel J, DaveD, Shah S , 2015 43

Sharma et al. 2011a44

Pradeep AR, Rao NS,Agarwal P, et al, 201246

Bansal C and Bharti V,2013 47

Thorat MK, PradeepAR, Pallavi B., 2011 48

Pradeep AR, Bajaj P,Rao NS, et al 2012 49

Femminella B, Iaconi MC,Di Tullio M, 2016. 76

Meta-analysis

RCT

Meta- analysis

RCT

RCT

Meta-analysis

RCT

RCT

RCT

RCT

CCT

RCT

RCT

RCT

The addition of autologous platelet concentrate (PRP and PRF) to open flapdebridement (OFD) may improve clinical parameters: horizontal andvertical clinical attachment level, probing depth and level of gingival marginin the treatment of mandibular class II furcation defects compared to OFDalone.

Significant improvement with PRF implies its role as a regenerative materialin treatment of furcation defects.

The results suggest that the use of PRF membranes did not improve the rootcoverage, keratinized mucosa width, or clinical attachment level of Millerclass-I and -II gingival recessions compared to the other treatmentmodalities.

The addition of PRF did not further develop the outcomes of coronallyadvance flap combined with a connective tissue graft treatment exceptincreasing the tissue thickness.

The additional application of PRF failed to improve root coverage afterdouble lateral sliding bridge flap in Miller’s Class I and II defects.

The meta-analysis showed clinically significant improvements in periodontalparameters such as clinical attachment levels and intra-bony defectreduction, and reduction in probing depth when IBDs were treated with PRFalone when compared to OFD.

PRF and PRGF platelet concentrate failed to augment the clinical effectsachieved with the xenograft alone in treating intrabony defects. Periodontaldefects could not retain extra-physiologic levels of GF suggested to beassociated with platelet concentrate.

PRF has shown significant results after 6 months, which are comparable toDFDBA for periodontal regeneration in terms of clinical parameters. PRF hasseveral advantages when used as a graft material for infrabony defects.

Greater pocket depth reduction and periodontal attachment level (PAL) gain,and bone fill at sites treated with PRF combined with conventional open-flapdebridement compared to conventional open-flap debridement alone.

The use of autologous PRF or PRP was effective in the treatment of 3-wallIBDs with uneventful healing of sites. Treatment with autologous PRF or PRPstimulated a significant increase in the PD reduction, GML, and bone fillcompared with OFD at 9 months.

PRF combined with demineralized-freeze dried bone allograft (DFDBA)demonstrated better results in probing pocket depth reduction and clinicalattachment level gain as compared to DFDBA alone in the treatment ofperiodontal intrabony defects.

Greater reduction in pocket depth, more clinical attachment level gain andgreater intra-bony defect fill at sites treated with PRF compared to open flapdebridement alone.

PRF when added to porous hydroxyapatite (HA) increases the regenerativeeffects observed with PRF in treatment of human three-wall intra-bonydefects.

The PRF-enriched palatal bandage significantly accelerates palatal woundhealing and reduces the patient’s morbidity.

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

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

induction of a strong and thick periosteum and gingiva. Theboosted periosteum functions as a true barrier between thesoft tissue and bone compartments, and constitutes probablythe best protection and regenerative barrier for the intrabonydefects.25 The NTR protocol25 is very simple and givesexcellent results in most clinical situations, with nocontraindication or risk of negative effects. However, in orderto get the best results, the choice and the quantity of theadequate bone substitute has yet to be determine in variousclinical configurations.

Theoretically, PRF can be used as a sole grafting materialor in combination with bone substitutes can be used as afilling material in intrabony defects, following GTRprinciples.12,119

PRF membrane is a solid material with the advantage thatit is easy to handle and to position in bony defects. PRFmembranes can also be used as a protection membraneafter the filling of the intrabony defect. (Figure 12a & 12b)In comparison to GTR membranes, PRF will undergo aquicker remodeling in situ than a resorbable collagenmembrane, but will promote a strong induction on theperiosteum and gingival tissue due to the slow release ofgrowth factors and other matrix proteins.63,64,65

GTR membranes are cell-proof barriers, whereas a PRFmembrane is a highly stimulating matrix, attracting cellmigration and preferential differentiation allowing new bloodvessel formation within the matrix, and also reinforcing thenatural periosteal barrier. The hard and soft tissues migrateand interact within the PRF matrix. The PRF matrix becomesthe interface between the tissues and therefore avoids themigration of the soft tissues deeper within the grafted defector augmented site. This biological characteristic is referredto as a competitive barrier.64

These bioactive interactions are very important duringtissue regeneration, since the periosteum covers the internalpart of the gingival flap and is a key actor of bone healingand gingival maturation. While GTR membranes block the

focused in the fields of improving clinical outcomes withtreatment of intra-bony periodontal pockets, furcation defects,gingival recession defects, and healing of connective tissuegraft sites in the palate. (Table 2)

Intrabony and furcation periodontal defectsThe regenerative and wound healing effects have been verypromising with PRF treating intrabony defects,41,42,43,44,45,46,47,48,49,50,51 (Table 3) The abovementionedclinical evidence is supported by several case studiesreporting on the successful application of PRF to regeneratebone and gingival tissues around teeth presenting withintrabony defects, 41,44,46,47,48,49,52,53,54,55,56,66 and furcationlesions.45,57,58,59,60,61

Another study has also reported on using PRF successfullyas a regenerative material in cases of aggressiveperiodontitis.60

Surgical periodontal therapy accompanying the placementof PRF in angular defects of aggressive periodontitis patientsshowed decreased probing pocket depth, increasedattachment level and radiographic bone fill when baselineand 9 month follow-up data was compared. Surgicalreconstructive therapy with placement of PRF in angulardefects can is suggested as an effective approach toenhance periodontal regeneration.60

Platelet gel acts as a stabilized blood clot and thereforerecommended as a perfect filling material for natural tissueregeneration and healing.25 Clinically, the general conceptof “Natural Tissue Regeneration” (NTR) and Natural BoneRegeneration (NBR)25 requires to fill the periodontal intrabonydefect with L-PRF, most times in association with a bonesubstitute used as a solid space maintainer, and then to coverthe filled intrabony defect with L-PRF membranes, used for theprotection of the grafted area and as a healing booster forthe soft tissues above the defects.25 The objective of this coveris not only to protect the blood clot and/or the fillingmaterial, like in the GTR concept, but also to promote the

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Figure 10a: Using PRF fragments mixedwith autogenous bone to fill spaces inguided bone regeneration procedure.

Figure 10b: Bone graft covered withcollagen membrane.

Figure 10c: Bone graft and collagenmembrane covered with multiple PRFmembranes.

Palatal bandagePRF membranes can also be used as a palatal woundbandage or protection membranes after harvestingconnective tissue grafts in the palate.76,77,78 Case studiesshow that PRF membrane used as a palatal bandage is anefficacious approach to protect the raw wound area of apalatal donor site and significantly accelerates palatalwound healing and reduces patient discomfort and healingtime.78,79,80

Inter-dental papilla augmentation A case study reported that PRF combined with bone graft forregeneration of interdental bone may contribute towardsimproved clinical success with

augmentation of lost dental papilla.81 The reconstructedpapilla in the new position was stable when reviewed at 3and 6 months postoperatively.

Oral SurgeryMost of the evidence-based research in the field of oral

periosteum healing potential and bone/gingival interactions,PRF membranes stimulate the periosteum’s regenerativeproperties. However, even if PRF membranes do not blockthe migration of the cells, no invagination of the soft tissueswithin the bone area were observed when PRF membranescovered a filled intrabony defect.62

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 ofavailable clinical trials, the clinical evidence indicate that PRFdoes not improve root coverage or increases the width ofkeratinized mucosa in Miller’s Class I and II gingivalrecessions, compared to other treatment modalities.However, cases have been reported where PRF wassuccessfully used for treating localized, 64,69,70,71,72,73 andmultiple74 gingival recessions. Another case study reportedthat the use of PRF membrane along with the VISTA techniqueallows clinicians to successfully treat multiple recessiondefects with optimal esthetic results and excellent soft tissuebiotype.75

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Figure 11a: PRF inserted into an osteotomy site before placingthe implant to facilitate bone healing.

Figure 11b: Implant wetted with PRF exudate containing growthfactors.

Figure 11c: Implant is inserted into the socket containing thePRF membrane

medication presenting a risk of osteonecrosis of the jaws, orpatients receiving anticoagulants.93

Delayed or compromised healing of extraction sockets ismostly related to an unstable blood clot within the socket. Insuch case a fibrin clot is simply placed in the socket, coveredwith a collagen plug or membrane and sutured. Placing PRFin a socket could amplify the natural coagulation processand enhance socket healing.7, 24,93, 83,84,88, 89,90,91,92

• Prevention of periodontal complications in 3rd molarsurgery

Complex third molar extractions frequently result in criticalsize bone defects and compromised healing impactingnegatively on the outcome of periodontal tissues distal of thesecond molar. When bone defects after extraction arecritical-sized (and often associated with cystic lesions), UsingPRF as a filling material or mixing PRF with a bone substitutein order to use a significant volume of solid biomaterial forfilling is considered as reliable option. These treatments arehowever no more simple dental extractions, and are often atthe border of guided bone regeneration (GBR) or bonegrafting. The use of a PRF as a filling material significantlypromotes soft tissue healing and also faster

regeneration of bone in these sites and neighboringperiodontal 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 minimalintervention closure of oro-antral communications, thus

surgery is primarily focused on enhancing bone healing82,83,84 and reducing postoperative complications following3rd molar extractions. 82,85,86 (Table 3) Research is alsoemerging on promoting healing of apico-marginal defects inroot end surgery. (Table 3) Numerous case and case seriesstudies have been reported that support the use of PRF invarious clinical applications in the field of oral surgery.

• Post-extraction socket augmentation and healingThe healing and remodeling of an extraction socket is

highly dependent on the initial stabilization of the blood clotand the quick gingival wound closure. This can be achievedby placing fibrin plug in the socket (with or without a bonesubstitute) and closing with a fibrin membrane. The use ofPRF as a post extraction sockets filling biomaterial isrecommended as a useful procedure in order to reduce theearly adverse effects of the inflammation, such aspostoperative pain,82,85,86 and to promote the soft tissuehealing and bone regeneration process.87

Clinical situations where post-extraction socketaugmentation with PRF is specifically indicated are for earlyor delayed implant placement; and immediate post-extractionimplant placement.7,20 ,21,24,26,83,88,89,90,91,92

• Reduce post-extraction complications in medicallycompromised cases

PRF can be used to minimize post-extraction complicationssuch as, osteitis, dry or infected sockets resulting from anddelayed or potentially compromised healing or bleedingsituations in systemic conditions such as such as withdiabetics; patient’s receiving on oral bisphosphonate

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Figure 12a: Intrabony defect after root planning and soft laserdecontamination, filled with bone putty and covered with a PRFmembrane to protect the grafted site area and to facilitate boneand soft tissue healing.

Figure 12b: Closure of flap over the grafted intrabony defect.

• Other oral surgical applications where PRF is used Alveolar cleft grafting

The use of PRF has also been reported in other therapiesincluding: alveolar cleft grafting.106

Bisphosphonate related oral necrosis of the jawRecent case reports suggested that PRF might stimulategingival healing and act as a barrier membrane betweenalveolar bone and the oral cavity, therefore offering a simple,though effective treatment for the closure of bone exposurein BRONJ. 107,108,109,120

Compromised wound healing situations (Diabetics)PRF has also been used as an adjuvant in themanagement of problematic chronic wounds.109 Theauthors have shown that growth factors in PRF areprotected from proteolytic degradation. This may beadvantageous in the treatment of chronic woundscharacterized by high proteinase activity.

eliminating the need to raise mucoperiosteal buccal slidingflaps.96 The technique for closure of an oro-antral fistula usingplatelet-rich fibrin is described by Argawal and co-workers.97

• Apical / root end surgeryPRF clot (gel) serves as an ideal scaffold in root-end

surgical procedures to enhance soft tissue healing and boneregeneration. 98,99,100,101 Other researcher’s report that PRFmay not necessarily improve the outcome of treatment. 102

The combination of PRF membrane as a matrix and MTA canprove to be an effective alternative for creating artificial root-end barriers and to induce faster peri-apical healing withlarge periapical lesions.103 It is suggested that thecombination of PRF and β-TCP for bone augmentation intreatment of periapical defects is also a more effective atincreasing healing time compared to using bone substitutematerial alone.104 PRF combined with an alloplastic bonesubstitute has been successfully used for the management ofcombined endodontic-periodontal lesions.105

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Application Reference Type of Study Evidence / Conclusion†

Reducingcomplications in3rd molarextractions

Enhance bonehealing after 3rdmolar extractions

Bone regenerationafter 3rd molarextractions

Bone healing andpost-operativecomplications after3rd molar surgery

Post-operativecomplicationsfollowing 3rd molarextractions

Root-end surgery /Healing ofapico-marginaldefects

ReferenceEshghpour et al,201485

Gurbuzer B,Pikdöken L, TunalıM, et al, 201083

Rao SG, Bhat P,K. S. Nagesh KS,et al, 2013 84

Singh A, Kohli M,Gupta N, 201282

Uyanık LO,Bilginaylar K,Etikan I., 201586

Dhiman M, KumarS, Duhan J, et al2015.102

RCT

CCT

CCT

CCT

CCT

RCT

PRF application may decrease the risk of alveolar osteitisdevelopment after mandibular third molar surgery.

PRF might not lead to enhanced bone healing in soft tissueimpacted mandibular third molar extraction sockets 4 weeksafter surgery.

PRF accelerate regeneration of bone after third molarextraction surgery in cases treated with PRF as compared tothe control group post operatively.

PRF is a valid method in promoting and accelerating soft andhard tissue wound healing and regeneration, and decreasingpain in mandibular 3rd molar extractions.

PRF and combination use of PRF and piezosurgery havepositive effects in reducing postoperative complications (painand trismus) after impacted third molar surgery.

A high success rate may be attained in apico-marginal defectswith endodontic microsurgery, and addition of PRF may notnecessarily improve the outcome.

Table 3. Evidence-based literature on the use of PRF in oral surgery

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

scaffold (fibrin matrix), platelets, growth factors, leukocytes,and stem cells. These key elements are all active componentsof PRF in whichever form, and when combined and preparedproperly are involved in the key processes of tissue healingand regeneration, whilst at the same time reducing adverseevents. Clinicians are using PRF is extensively and successfullyin various clinical applications in dental implantology,periodontology, maxillofacial and oral surgery, and lately inregenerative endodontics, to promote wound healing andtissue regeneration. The use of PRF in revitalization,revascularization, and regenerative pulp therapies arecurrently attracting a lot of attention and several case studiesin the field of regenerative endodontics are being reported.These applications however still need to be validated withrobust clinical trials.

One of the clinical limitations to note is the heterogeneityin the quality of platelets and blood components due to useof different PRF preparation protocols in the various studiesreviewed. Irrespective of the protocol used all studies haveall reported successful outcomes with regards to soft and bonetissue healing and regeneration. It should also be noted thatat this stage in time there is not a single RCT or CCT tocompare the effectiveness of A-PRF or L-PRF protocols.Furthermore, in vitro studies that claim superiority or inferiorityof a specific PRF preparation have yet to be validated byindependent clinical trials. The future of PRF and itapplications in clinical dentistry, especially in the field of softtissue and bone regeneration has enormous implications, butdeveloping and strengthening its role in dentistry is dependenton its coherence and scientific clarity. The clinicaleffectiveness of different PRF preparation protocols in variousclinical settings remains to be validated with a greater numberof independent and robust RCT’s, preferably with a split mouthdesign, and larger sample sizes. Independent, coherent andscientific validation of PRF is needed to enhance the potentialof this technology, thereby extending its therapeuticapplications with improved successful and predictableoutcomes for the benefit of the patient. PRF technology is inits infancy and will in future have a big impact in dentistry.

The benefits derived from the using PRF in various clinicalapplications for promoting wound healing and tissueregeneration, its antibacterial and anti-haemorrhagic effects, thelow risks with its use, and the availability of easy and low costpreparation methods, should encourage more clinicians to adoptthis technology in their practice for the benefit their patients.

References1. Kawase T. Platelet-rich plasma and its derivatives as

promising bioactive materials for regenerative medicine: basicprinciples and concepts underlying recent advances.Odontology 2015; 103: 126-135.

Regenerative endodontic therapy Regenerative endodontic procedures are widely being addedto the current armamentarium of pulp therapyprocedures.105,110,111,112,113,114

These biologically based procedures are designed torestore function of a damaged and non-functioning pulp bystimulation of existing dental pulp stem and progenitor cellspresent in the root canal under conditions that are favorableto their differentiation.110,111

• Management of open apexRecent 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 endodonticmanagement of an open apex. 112,115,116

It is hypothesized that the combination of MTA and PRF mayhave a synergistic effect on the stimulation of odontoblasticdifferentiation of stem cells.

• Revascularization and revitalizationRevascularization is the most studied and successful

approach of regenerative endodontics.115 Revitalization ofnecrotic infected immature tooth is possible under conditionsof total canal disinfection combined with the additive effectof PRF. 117,118 PRF is proposed as an ideal biomaterial for pulp-dentin complex regeneration because it is a potentially validscaffold material containing leukocyte and growth factors tofacilitate tissue healing and regeneration in immature necroticteeth in children. 115,116,117

Repair and regenerative potential of PRF, and enhancedcellular metabolism with laser bio stimulation, in combinationwith the sealing ability of MTA enhances the clinical successoutcomes in pulpotomy and apexification procedures.115

Revitalization, revascularization, and regenerative pulptherapies still needs to be validated with robust clinical trials.

Conclusion PRF is increasingly being investigated and used by clinician’sworldwide as an adjunctive autologous biomaterial topromote bone and soft tissue healing and regeneration. PRFhas also grabbed the attention of clinicians because thisbiomaterial is derived from the patients’ own blood; is easyto make at chair-side, easy to use within the daily clinicalroutine; widely applicable in dentistry with virtually no risk ofrejection; whilst being financially realistic for the patient andthe practice. The 3D architecture of the fibrin matrix providesthe PRF membrane with great density, elasticity, flexibility andstrength that are excellently suited for handling, manipulationand suturing. The gold standard for in vivo tissue healing andregeneration requires the mutual interaction between a

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A comprehensive clinical review of Platelet Rich Fibrin ... · PDF file64 INTERNATIONAL DENTISTRY – AFRICAN EDITION VOL. 6, NO. 5 A comprehensive clinical review of Platelet Rich