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REVIEW ARTICLE
Year : 2019  |  Volume : 11  |  Issue : 6  |  Page : 126-130  

Platelet-rich plasma and platelet-rich fibrin in periodontal regeneration: A review


1 Department of Stem Cells and Regenerative Medicine; Department of Oral and Maxillofacial Pathology, Sree Anjaneya Institute of Dental Sciences, Calicut, Kerala, India
2 Department of Oral Medicine and Radiology, Sree Anjaneya Institute of Dental Sciences, Calicut, Kerala, India
3 Department of Oral Pathology and Microbiology, Indira Gandhi Institute of Dental Sciences, Sri Balaji Vidyapeeth Deemed To Be University, Pillayarkuppam, Puducherry, India
4 Department of Periodontics, Sree Anjaneya Institute of Dental Sciences, Calicut, Kerala, India

Date of Web Publication28-May-2019

Correspondence Address:
Dr. Sunil Paramel Mohan
Prof. and HOD, Department of Oral Pathology and Microbiology, Director of Department of Stem Cells and Regenerative Medicine, Sree Anjaneya Institute of Dental Sciences, Calicut, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JPBS.JPBS_41_19

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   Abstract 

Platelet concentrates (PCs; platelet-rich plasma and platelet-rich fibrin) are autologous bioactive substances that have found varied application in medical and dental fields, particularly in oral and maxillofacial surgery, plastic surgery, and sports medicine. The rationale of these technologies is to extract all the elements from patient’s own blood sample, which could be used to improve healing by promoting tissue regeneration. PCs have evolved a long way since its introduction in 1954. PCs have been used successfully in periodontics and implant dentistry. However, the preparation protocol, processing time, transfer of concentrates, centrifugation temperature, vibration, etc., being not standardized are various factors for the mixed results reported in the literature. This review intends to discuss evolution of PCs, their preparation techniques, and their clinical and technical aspects and applications.

Keywords: Fibrin glue, leukocyte and platelet-rich fibrin, platelet concentrates, platelet-derived growth factors, platelet-rich fibrin, platelet-rich plasma, sticky bone


How to cite this article:
Mohan SP, Jaishangar N, Devy S, Narayanan A, Cherian D, Madhavan SS. Platelet-rich plasma and platelet-rich fibrin in periodontal regeneration: A review. J Pharm Bioall Sci 2019;11, Suppl S2:126-30

How to cite this URL:
Mohan SP, Jaishangar N, Devy S, Narayanan A, Cherian D, Madhavan SS. Platelet-rich plasma and platelet-rich fibrin in periodontal regeneration: A review. J Pharm Bioall Sci [serial online] 2019 [cited 2019 Jul 22];11, Suppl S2:126-30. Available from: http://www.jpbsonline.org/text.asp?2019/11/6/126/258872




   Introduction Top


Periodontitis is an inflammatory disease of the periodontal tissues, which is characterized by loss of support of the affected teeth, specifically periodontal ligament fibers and the bone into which they are inserted. Regeneration or repair is the expected healing outcome following periodontal therapy. This depends on two crucial events: availability of cell types needed and presence or absence of signals necessary to recruit and stimulate the cells. The cascade of healing of any wound is initiated by clot formation, followed by proliferative stage and maturative stage. Growth factors favor wound healing by promoting proliferation of cells (mitogenesis), migration of cells (chemotaxis), and stimulation of new blood vessel formation (angiogenesis).[1]

The use of blood-derived products to heal wounds began in 1970 when fibrin glues or fibrin sealants, which were formed by polymerizing fibrinogen with thrombin and calcium, were introduced. Fibrin glue had clinical applications such as topical hemostasis and tissue sealing, soft tissues, and melting agents for particulate bone substitutes. As the concentration of fibrinogen in plasma is less, the stability and quality of fibrin glue were low.[2],[3] Variation in its composition and characteristics, lower resistance to physical stresses, costly processing and associated with a risk of viral transmission are its drawbacks.

Platelets contain biologically active proteins that bind on to a developing fibrin mesh or to the extracellular matrix. The proteins thus create a chemotactic gradient for recruitment of stem cells. These stems cells undergo differentiation, and promote healing by regeneration. Hence, the use of autologous platelet concentrates opens a promising treatment option in the field of periodontal regeneration, especially in clinical situations demanding rapid healing.[4] The regenerative potential of platelets was initially introduced in 1974 by Ross et al.[5] It was proposed that platelet-derived growth factor (PDGF) serves as growth factor on fibroblasts, smooth muscle cells, and glial cells.

The application of platelet concentrates was initially limited to treatment and prevention of hemorrhage due to severe thrombopenia. As its scope in medical application expanded, an idea to combine the fibrin sealant properties with the growth factors in platelets was tried for wound healing and regeneration of tissues.


   Platelets Top


Platelets are enucleated hematologic component derived from bone marrow precursor cells: megakaryocytes. It measures 2–3 µm in diameter, and the cell organelles constitute granules, few mitochondria, and prominent membrane structures. It has a surface-connected canalicular system and a well-stacked tubular system, which help in expulsion of growth factors especially PDGF, upon activation of platelets [Figure 1].[6]
Figure 1: Structure of platelet (Courtesy: postgradmedj-2001-October-77-912-e6-F1.large)

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The α granules are spherical or oval membrane-enclosed units with the cytoplasm. Diameter of the granules range from 200 to 500nm each. These macromolecules constitute 15% of the total platelet volume[7] while being the storage pool of proteins important in various stages of wound healing: PDGF, transforming growth factor (TGF-β), and insulin-like growth factor (IGF-I).[8] PDGF promotes protein synthesis in osseous tissues and proliferative stage in wound healing along with TGF-β. TGF-β has chemotactic effect on osteoblastic cells and endothelial cells, inhibitory effects on osteoclasts, and initiates woven bone formation. IGF-1 stimulates proliferation of osteoblasts and increases expression of osteocalcin for matrix synthesis. A combination of IGF-1 and PDGF checks the rate and quality of wound healing [Figure 2].[9]
Figure 2: Growth factors released from α granules and their function (Courtesy: researchgate.net). BMP = bone morphogenic protein, VEGF = vascular endothelial growth factor, PGDF = platelet-derived growth factor, TGF-β = transforming growth factor

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The α granules after activation fuse with the cell membrane. Upon activation, the proteins are secreted, bind to transmembrane receptors of the target cells, trigger the intracellular signal proteins, and influence the expression of a gene sequence, thus promoting healing.

Classification of platelet concentrates [Figure 3]:
Figure 3: Platelet concentrates (Courtesy: researchgate.net)

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  1. Platelet-rich plasma (PRP), the first-generation platelet concentrates, showed positive results; however, its limitations included complexpreparation protocol and the risk of cross infection from bovine thrombin.
  2. Platelet-rich fibrin (PRF) also called as Choukrounís platelet-rich fibrin named after its inventor.



   Platelet-Rich Plasma Top


PRP is a first-generation platelet concentrate containing high concentration of platelet but minimal amount of natural fibrinogen. The α granules release growth factors within 3–5 days of platelet activation, which sustain their stimulation of proliferative phase for 10 days after release.

Platelet-rich plasma procurement

PRP is processed from autologous blood. The cell separator withdraws 400–450mL of autologous blood through a central vein catheter. Before the blood is placed in the centrifuge, sodium citrate dextrose is added to the blood at a ratio of 1:5 for the purpose of anticoagulation through calcium binding followed by a two spin centrifugation. The tube is centrifuged at 1300rpm for 10 minutes (soft spin). A second centrifugation is performed at 2000rpm for 10 minutes (hard spin). After 10 minutes of centrifugation, three layers are obtained. The least dense layer, which is platelet-poor plasma, is about 45% of the sample; middle layer consists of RBCs and is about 40% of the sample; and lower layer is the PRP, which makes up around 15% of the sample. It is also called the buffy coat because of its white or buffy appearance.

Each mix draws 7mL PRP + 1mL CaCl2 +1000 units of topical bovine thrombin + 1mL air respectively (the CaCl2 and thrombin initiate the coagulation process and easy handling). It is then agitated for 6–10 seconds to initiate clotting and is immediately used onto the graft site or added to particulate graft. It can also be gelled into a membrane that can be placed into a surgical site.

The architecture of PRP constitutes bilateral junctions (condensed tetra molecular) constituted with strong thrombin concentrations; thickening of fibrin polymers forming a rigid network, unfavorable to cytokine enmeshment; and cellular migration.[10] Periodontal applications of PRP are periodontal defect treatment, root coverage procedures, ridge augmentation grafting, guided bone regeneration, sinus lift grafting, and implant surgery. The clinical application of PRP also extends to mandibular and maxillary reconstruction (tumor and trauma related defects), blepharoplasty, dermal fat grafts, and orthopedic surgery.

Advantages of using PRP are the following: brings cytokines and growth factors to the site, which helps in rapid regeneration in a manner that would not occur with fibrin glue because of the presence of platelets; free from concerns over transmissible disease; and convenient for patient. However, its limitations are lack of standardization in PRP preparation protocol, variation in storage time of different platelet concentration, and life-threatening coagulopathies (bovine thrombin can trigger antibodies to clotting factors).

In a recent systemic review, Plachokova et al.[11] found evidence for beneficial effects of PRP in the treatment of periodontal defects. Evidence for beneficial effects of PRP in sinus elevation appeared weak and no conclusions could be drawn about its other applications in dentistry. Meanwhile, Kotsovilis et al.[12] obtained diverse outcomes for the efficacy of PRP with various therapeutic bioactive agents/procedures, possibly suggesting that the specific selection of agents/procedures combined with PRP could be important. A meta-analysis by Bae et al.[13] suggested that there was sufficient evidence to support the use of PRP for bone formation on a sinus bone graft, whereas its effect on the implant survival was less significant.


   Platelet-Rich Fibrin Top


An autogenous living biomaterial, developed in France by Choukroun et al.[14] (2001), is a second-generation platelet concentrate. It has gained popularity as it accelerates soft- and hard-tissue healing. Its advantages over PRP are ease of preparation/application, minimal expense, and lack of biochemical modification (no bovine thrombin or anticoagulant is required).[14] A major advantage of PRF is that it has a simple preparation protocol. The difference between natural blood clot and PRF is that the latter is more homogeneous and stable and easy to handle and place.[15]

Protocol for platelet-rich fibrin preparation

The protocol tries to accumulate platelets and the released cytokines in a fibrin clot.[16] For preparation of PRF, only centrifuged blood without any addition of anticoagulant and bovine thrombin is required. Blood sample is taken without anticoagulant in 10-mL tubes in a glass or glass-coated plastic tube and immediately centrifuged at 3000rpm for 10 minutes.[17] The resultant product consists of the following three layers: top-most layer consisting of an acellular plasma, PRF clot in the middle, and a red corpuscle base at the bottom [Figure 4].[18]
Figure 4: Layers obtained after centrifugation (Courtesy: www.naturaldentistassociates.com)

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Mazor et al.[8] suggested that on compression between two sterile gauzes or in a specific PRF tool, clot could be transformed into a membrane. The contact of blood with a silica surface activates the clot polymerization process; this activation reduces the risk of cytotoxicity compared with the use bovine thrombin used for PRP preparation.[19] Compared to PRP, structurally it has equilateral junctions (connected trimolecular), fine and flexible fibrin network that support cytokines enmeshment and cellular migration. This three-dimensional organization provides elasticity, flexibility, and strength to PRF membrane.[20] Advantages of PRF as a bioactive substitute include less technical skills, minimal biochemical modification, cost effectiveness, increased incorporation of the circulating cytokines in the fibrin meshes, and slow polymerization, thus accelerating healing, better structural integrity.[21] Reported limitations of PRF are low quantity and requires immediate use after preparation because it can lose the structural integrity by shrinkage due to dehydration.[19] Leukocytes present adversely alter its biologic properties, and bacterial contamination occurs on storage.[22] Being a promising line of treatment in the direction of tissue regeneration, various authors have suggested different clinical application of PRF. The concept of “natural bone regeneration” was suggested by Simonpieri et al.,[15] which indicates reshaping the whole alveolar bone and the restoration of gingival volume and peri-implant bone. Chang and Zhao[23] suggested favorable clinical results with PRF in the treatment of periodontal infrabony defects. Clinical studies achieved promising results in maxillary sinus floor augmentation and sealing sinus membrane perforation.[24] Combination of PRF and bone graft reduces the volume of bone substitute and improves revascularization by its property of angiogenesis. Simonpieri et al.[15] noted good clinical results when several layers of PRF was used with immediate implants.

The literature reports that some other possible applications of osteitis reduction were found in surgical sites of the third molars[25] adjunct to wound healing of donor site of free gingival graft[26] in pulp revascularization procedures of immature permanent tooth, reconstruction after cancer surgery.[27] High quantities of L-PRF can be produced in large quantities using specific multiple centrifuge tubes for larger surgeries.[28] The new advanced PRF releases higher amount of growth factor that leads to the accumulation of significant amount of proteins for a long time.[29]Gassling et al.[28] reported that PRF appears to be superior to collagen as a scaffold for cell proliferation, and in vitro cultivation of periosteal cells for bone tissue engineering can be procured with PRF membranes.[30]


   Conclusion Top


PRF, a new generation of platelet concentrate, is a novel step in regenerative periodontal treatment with simplified processing and without biochemical modification. Apart from its application in dentistry, PRF is also been used in various medical fields: orthopedic and plastic surgery. Although merits and demerits of PRF have been confirmed by various systematic reviews and meta-analysis, numerous prospective studies have yet to be explored. Clinical studies in cooperating PRF for various treatments are quite encouraging; however, further studies are necessary to support its common use in routine dental practice with high clinical efficacy and long-term stability.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Kanakamedala A, Ari G, Sudhakar U, Vijayalakshmi R, Ramakrishnan T, Emmad P. Treatment of a furcation defect with a combination of platelet-rich fibrin (PRF) and bone graft—A case report. ENDO (LondEngl) 2009;3:127-35.  Back to cited text no. 1
    
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Prakash S, Thakur A. Platelet concentrates: Past, present and future. J Maxillofac Oral Surg 2011;10:45-9.  Back to cited text no. 8
    
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Plachokova AS, Nikolidakis D, Mulder J, Jansen JA, Creugers NH. Effect of platelet-rich plasma on bone regeneration in dentistry: A systematic review. Clin Oral Implants Res 2008;19:539-45.  Back to cited text no. 11
    
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Kotsovilis S, Markou N, Pepelassi E, Nikolidakis D. The adjunctive use of platelet-rich plasma in the therapy of periodontal intraosseous defects: A systematic review. J Periodontal Res 2010;45:428-43.  Back to cited text no. 12
    
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Bae JH, Kim YK, Myung SK. Effects of platelets rich plasma on sinus bone graft: meta-analysis. Periodontol 2011;8:660-7.  Back to cited text no. 13
    
14.
Choukrou J, Adda F, Schoeffler C, Vervelle A. Une opportunitéen paro-implantologie: le PRF. Implantodontie 2001;42:55-62.  Back to cited text no. 14
    
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Simonpieri A, Del Corso M, Vervelle A, Jimbo R, Inchingolo F, Sammartino G, et al. Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 2: Bone graft, implant and reconstructive surgery. Curr Pharm Biotechnol 2012;13:1231-56.  Back to cited text no. 15
    
16.
Mazor Z, Horowitz RA, Del Corso M, Prasad HS, Rohrer MD, Dohan Ehrenfest DM. Sinus floor augmentation with simultaneous implant placement using choukroun’s platelet-rich fibrin as the sole grafting material: A radiologic and histologic study at 6 months. J Periodontol 2009;80:2056-64.  Back to cited text no. 16
    
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Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, et al. Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part I: Technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:e37-44.  Back to cited text no. 17
    
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Agrawal M, Agrawal V. Platelet rich fibrin and its applications in dentistry—A review article. Natl J Med Dent Res 2014;2: 51-8.  Back to cited text no. 18
    
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Kumar RV, Shubhashini N. Platelet rich fibrin: A new paradigm in periodontal regeneration. Cell Tissue Bank 2013;14:453-63.  Back to cited text no. 20
    
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Patel J, Deshpande N, Shah M, Dave D, Shah C, Shah S. PRF-from self to self. Res Rev J Dent Sci 2013;2:30-4.  Back to cited text no. 21
    
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Gupta V, Bains BK, Singh GP, Mathur A, Bains R. Regenerative potential of platelet rich fibrin in dentistry: Literature review. Asian J Oral Health Allied Sci 2011;1:22-8.  Back to cited text no. 22
    
23.
Chang YC, Zhao JH. Effects of platelet-rich fibrin on human periodontal ligament fibroblasts and application for periodontal infrabony defects. Aust Dent J 2011;56:365-71.  Back to cited text no. 23
    
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Toffler M, Toscano N, Holtzclaw D, Corso MD, Dohan Ehrenfest DM. Introducing Choukroun’s platelet rich fibrin (PRF) to the reconstructive surgery milieu. J Implant Clin Adv Dent 2009;1:21-30.  Back to cited text no. 24
    
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Kulkarni MR, Thomas BS, Varghese JM, Bhat GS. Platelet-rich fibrin as an adjunct to palatal wound healing after harvesting a free gingival graft: A case series. J Indian Soc Periodontol 2014;18:399-402.  Back to cited text no. 26
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Reyes M, Montero S, Cifuentes J, Zarzar E. Extraction technique and surgical use of the plasma rich in growth factors (P. R.G.F.): Update. Rev Dent Chile 2002;93:25-8.  Back to cited text no. 27
    
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Gassling V, Douglas T, Warnke PH, Açil Y, Wiltfang J, Becker ST. Platelet-rich fibrin membranes as scaffolds for periosteal tissue engineering. Clin Oral Implants Res 2010;21: 543-9.  Back to cited text no. 28
    
29.
Ehrenfest DMD, Rasmusson L, Albrektsson T. Classification of platelet concentrates: From pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin. Rev Dent Chile 2007;73:25-8.  Back to cited text no. 29
    
30.
Kobayashi E, Sawada K, Schaller, Miron RJ. Comparative release of growth factors from PRP, PRF and advanced PRF. Clin Oral Investig 2016;20:2353-60.  Back to cited text no. 30
    


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