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Platelet Rich Fibrin – A Review

Dr. Ojas Anand Gajbhiye M.D.S. (Prosthodontist and Implantologist), Nagpur, Maharashtra. Email id- [email protected]

Dr. Ayushi S Gurharikar, 2nd yr Post Graduate Student, Pediatric and Preventive Dentistry, Nagpur, Maharashtra. Email id - [email protected]

Dr. Raksha Kusumbe, BDS, MDS PG 2year, SDKS Dental College, Nagpur, Maharashtra.

Dr. Ashima Trivedi, Consultant Periodontist, Trivedi Dental Centre, Jabalpur, Madhya Pradesh

Dr. Faizan A khan, Post graduate student, Department of Periodontics and Implantology, College of Dental Science and Research Center, Ahmedabad

Dr. Pratik Surana, Senior lecturer, Department of Pedodontics and Preventive Dentistry, Maitri College of Dentistry and Research Center, Durg, Chhattisgarh

Corresponding address- Dr Ojas Anand Gajbhiye M.D.S.

(Prosthodontist and Implantologist), Nagpur, Maharashtra. Email id- [email protected]

Abstract: Platelet rich fibrin (PRF) is a biomaterial derived from human blood, part of a platelet concentrate obtained through a centrifuge separating it. Its use is quite common in medicine and dentistry for recovery and healing in surgeries and for tissue regeneration. Thus Present review of literature aims to provide details of PRF preparation and its application in dentistry.

Keywords: Platelet rich fibrin, PRF, Dentistry

Introduction: Platelet-rich fibrin is a second generation platelet concentrate and is defined as an autologous leucocyte and platelet-rich fibrin biomaterial. Platelet rich fibrin affects cellular activities at genetic and cellular levels. PRF membrane consists of a fibrin 3-D polymerized matrix in a specific structure, with the incorporation of almost all the platelets and more than half of leucocytes along with growth factors and circulating stem cells.1

It was first described by Dr. Joseph Choukroun in France to promote wound healing in implants. Currently, the studies have been focussed on the use of an autogenous material called Platelet Rich Fibrin that provides an osteoconductive scaffold along with growth factors to stimulate patient’s own cells towards a regenerative response.2

It can be obtained from blood with the help of a simple process. PRF is basically a concentrate of growth factors that promote wound healing and regeneration which is used in

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various disciplines of dentistry to repair various lesions and regenerate dental and oral tissues.3 Thus Present review of literature aims to provide details of PRF preparation and its application in dentistry.

Guideline for preparation of PRF

The protocol tries to accumulate platelets and the released cytokines in a fibrin clot. PRF protocol requires only centrifuged blood without any addition of anticoagulant and bovine thrombin. Then, a blood sample is taken without anticoagulant in 10-mL tubes in a glass or glass-coated plastic tube, then immediately centrifuged at 3,000 rpm for 10 minutes.4

The resultant product consists of the following three layers:

● Top most layer consisting of cellular plasma.

● PRF clot in the middle.

● Red corpuscle base at the bottom of tube.

PRF membrane can be obtained by squeezing out the liquids present in the fibrin clot.

Liquid removal from the PRF fraction can be done through mechanical pressure between gauze layers resulting in a fairly solid, gel-like material that can be used in various clinical applications as a filling material or as a suturing membrane. PRF membrane can also be prepared by compressing PRF clot in special tools like “PRF Box” resulting in standardized membranes of constant thickness and size along with PRF exudates. PRF exudates contains good amount of growth factors (TGF-b1, PDGF-AB, VEGF etc.), matrix glycoproteins (fibronectin, vitronectin etc.) and proteins specialized in increasing cell attachment to biomaterials and titanium; therefore can be used for biomaterial impregnation, rinsing surgical sites, hydration of graft materials and for storage of autologous grafts.5

Table no 1: Difference between PRP and PRF6

PRP PRF

Generation First generation Second generation

Based on processing Use of bovine thrombin and No anticoagulant used technique calcium chloride (anticoagulants)

Sudden fibrin polymerization Slow natural polymerization on depending on the amount of contact with glass particles of the Based on architecture surgical additives (thrombin and test tube

calcium results in physiologic thrombin

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chloride) concentration

There is immediate release of Growth factors are released slowly Based on biological

growth factors over a period of 7 or more days property

Concern over the use of bovine No coagulopathies and no thrombin, bovine factor Va may be bleeding episodes An in vitro

a contaminant in certain bovine study showed that PRF is superior Based on thrombin commercial preparations, to PRP, considering the expression therapeutic concern antibodies to bovine factor Va may of alkaline phosphatase and

cross react with human factor Va induction of mineralization, and may produce coagulopathies caused markedly by release of

and rare bleeding episodes TGF-β, and PDGF-AB

Table no 2: Advantage of PRF over PRP7

 No Biomechanical handling of blood.

 Simplified cost effective process and use of bovine thrombin and use of anticoagulant not required.

 Favourable healing due to slow polymerization.

 More efficient cell migration and proliferation.

 PRF has supportive effect on immune system.

PRF helps in haemostasis .

Table no 3: Growth factors found in PRF and their function7

Growth factor Functions

Platelet-derived growth factors (PDGFs) Specific roles include proliferation of cells, cellular migration and collagen production for remodeling of extra-cellular matrix to repair the wound.

Transforming growth factor β1 (TGF-β1) Tissue repair, extracellular matrix synthesis and immune modulation. Specific roles played by TGF-β1 includes angiogenesis, re-epithelization and regeneration of connective tissue. Due to bone morphogenetic proteins (BMPs) being part of TGF family. They also play role in bone formation.

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Vascular endothelial growth factor (VEGF) Primary function is angiogenesis. Also, plays a role in tissue remodeling.

Endothelial growth factor (EGF) Proliferation and multiplication of endothelial and mesenchymal cells, which leads to epithelization Insulin-like growth factors (IGFs) Cell-protective in nature and participates in

proliferation and differentiation of a variety of cells.

Application of PRF in dentistry

1. In Periodontology: PRF, shows compelling data in various in vitro and clinical studies. It can be utilized in various procedures such as management of intrabony defects, gingival recession, furcation defects, extraction socket preservation, and accelerated healing of wound.

PRF used either in combination with bone grafts (bovine porous bone mineral, nanocrystalline hydroxyapatite, and demineralized freeze-dried bone allograft [DFDBA]) or pharmacologic agents such as metformin gel was found to be more effective in terms of improvements in clinical parameters and radiographic defect depth reduction compared to when bone grafts or metformin used alone. The use of PRF alone or in combination with other biomaterials provided safe and promising results in the form of improvements in clinical and radiographic parameters in the management of periodontal osseous defects and hard tissue preservation of extraction socket.9

2. In Oral surgery: Tooth extraction or avulsion is logically the most important and common surgical situation encountered in oral and maxillofacial surgery, and as old as human kind itself. This surgical procedure is more or less complex, but the outcomes are globally good. The use of a surgical adjuvant may seem unnecessary, but there are 3 configurations where a healing booster may be highly interesting.

 Post surgical follow up following complex extractions or third molar surgery, being very often associated with pain and swelling.

  The second situation is when implant restoration is considered after avulsion.

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 The third situation is the avulsion in patients with general or local pathologies that interfere with bleeding or healing. Particularly true in patients on anticoagulants/bisphosphonates.

The systematic use of a platelet concentrate in order to avoid painful events, promote bone regeneration and improve gingival healing may become a relevant principle in oral surgery.10

3. In Pediatric dentistry: The advantage with PRF is stimulation and healing of the tissues, this could help in PRF finding a major place in various treatment modalities done in pediatric dentistry.11

Pulp capping- Platelet Rich Plasma could be an effective material used for direct pulp capping due to its excellent wound healing, tissue regeneration and osteogenic properties.

  Pulpotomy Cytotoxicity and mutagenic effects have always been major

disadvantages discovered with the use of formocresol, as a pulpotomy agent. Platelet Rich Plasma with its low toxic effects and increased tissue regeneration showed

excellent clinical results. A study conducted by Damle et al. (2004)12 compared PRP and Calcium Hydroxide and found 100% success rate with Platelet Rich Plasma.

Another study with Nagasaki et al. (2007)13 compared PRP vs Hydroxiapetite crystals, and found PRP to be much superior.

4. In Endodontics: Regenerative endodontic procedures require the use of appropriate scaffolds to provide a spatially correct position of cell location, regulate differentiation, proliferation, or metabolism of the stem cells. Platelet-rich fibrin is one such scaffold which is currently gaining popularity in the field of regenerative endodontics. Mittal et al. (2019) compared the regenerative potential of PRF and artificial scaffolds (commercially available collagen, placentrex, and chitosan) in necrotic immature permanent teeth. They concluded that PRF and collagen are better scaffolds than placentrex and chitosan for inducing apexogenesis in immature necrotic permanent teeth.14

5. In Implantology: In implantology, the use of this biomaterial has as main objective the increase of the surrounding bone tissue for implant placement, since the lack of adequate thickness, as well as the proximity of the maxillary sinuses in the maxilla, and the inferior alveolar nerve in the mandible are the most frequent problems that

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professionals in this area face. This has led to surgical bone augmentation procedures, such as breast lift and guided bone regeneration, which work in conjunction with the implant system in order to generate sufficient bone that supports implant placement.

New therapeutic forms can be developed with the addition of PRF to graft materials.15,16

Advantages of PRF4

1. Its preparation is a simplified and efficient technique, with centrifugation in a single step, free and openly accessible for all clinicians.

2. It is obtained by autologous blood sample.

3. Minimized blood manipulation.

4. It does not require the addition of external thrombin because polymerization is a com- pletely natural process, without any risk of suffering from an immunological reaction.

5. It has a natural fibrin framework with growth factors within that may keep their activity for a relatively longer period and stimulate tissue regeneration effectively.

6. It can be used solely or in combination with bone grafts, depending on the purpose.

7. Increases the healing rate of the grafted bone.

8. It is an economical and quick option compared with recombinant growth factors when used in conjunction with bone grafts.

9. Used as a membrane, it avoids a donor site surgical procedure and results in a reduction in patient discomfort during the early wound-healing period.

10. The studies of PRF present it to be more efficient and with less controversies on its final clinical results when compared to PRP.

Disadvantages of using PRF4

1. The final amount available is low because it is autologous blood.

2. The success of the PRF protocol depends directly on the handling, mainly, related to blood collection time and its transference for the centrifuge.

3. Need of using a glass-coated tube to achieve clot polymerization.

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4. Possible refusal of treatment by the puncture required for blood collection.

5. Only needs a minimal experience of clinician for PRF manipulation

Conclusion: The PRF has wide applicability, from Dentistry to Medicine, with excellent results in the short term; all studies show the safety in its use for maxillofacial application.

Several studies have demonstrated safe and promising results, without contradictory findings, related to the use of PRF alone or in combination with other biomaterials. However, more long term studies are required to evaluate deeper knowledge about the efficacy of this biomaterial and to optimize its use in routine clinical dentistry.

References

1. Raaj V, Gautam A, Abhishek, Kumari P. Platelet-Rich Fibrin (PRF): A New Generation Paltelet Concentrate. Int J Dent Med Res 2015;1(6):164-167.

2. Kanakamedala A, Ari G, Sudhakar U, RajaramVijayalakshmi, 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(2):127–135.

3. Agrawal M, Agrawal V. Platelet Rich Fibrin and its Applications in Dentistry- A Review Article. Natl J Med Dent Res 2014; 2(3): 51-58.

4. Borie E, Oliví DG, Orsi IA, Garlet K, Weber B, Beltrán V, Fuentes R. Platelet-rich fibrin application in dentistry: a literature review. Int J Clin Exp Med. 2015 May 15;8(5):7922-9.

5. Corso MD, Toffler M, David M, Ehrenfest D. Use of autologous leukocyte and platelet rich fibrin (L-PRF) membrane in post avulsion sites: an overview of

Choukroun’s PRF. The journal of implant and advanced clinical dentistry 2010;

1(9):27-35.

6. Bansal S, Garg A, Khurana R, Chhabra P. Platelet-rich fibrin or platelet-rich plasma – Which one is better? An opinion. Indian J Dent Sci 2017;9:S49-52.

7. Saluja H, Dehane V, Mahindra U. Platelet-Rich fibrin: A second generation platelet concentrate and a new friend of oral and maxillofacial surgeons. Ann Maxillofac Surg. 2011 Jan;1(1):53-7

8. https://www.intechopen.com/books/periodontology-and-dental-implantology/platelet- rich-fibrin-utilization-in-the-treatment-of-periodontitis.

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Periodontal Therapy - A Systematic Review. J Int Soc Prev Community Dent. 2017 Sep-Oct;7(5):227-233.

10. Mohammed Imran et al.; Saudi J. Oral.Dent. Res.; Vol-2, Iss-7(Jul, 2017):174-179.

11. Nakashima M, Akamine A. The application of tissue engineering to regeneration of pulp and dentin in endodontics. J Endod. 2005; 31:711–718.

12. Kalaskar RR, Damle SG. Comparative evaluation of lyophilized freeze dried platelet derived preparation with calcium hydroxide as pulpotomy agents in primary molars. J Indian Soc Pedod Prev Dent 2004;22:24-9.

13. Ide Y, Nagasaki N, Tomioka R, Suito M, Kamiya T, Maeshima M. Molecular properties of a novel, hydrophilic cation-binding protein associated with the plasma membrane. J Exp Bot. 2007;58:1173-83.

14. Mittal N, Parashar V. Regenerative Evaluation of Immature Roots using PRF and Artificial Scaffolds in Necrotic Permanent Teeth: A Clinical Study. The journal of contemporary dental practice. 2019; 20(6):720-6.

15. Raes F, Cosyn J, Crommelinck E, Coessens P, De Bruyn H (2011) Immediate and conven- tional single implant treatment in the anterior maxilla: 1-year results of a case series on hard and soft tissue response and aesthetics. J Clin Periodontol 38: 385-394.

16. Lekovic V, Milinkovic I, Aleksic Z, Jankovic S, Stankovic P, et al. (2012) Plateletrich fibrin and bovine porous bone mineral vs. platelet-rich fibrin in the treatment of intrabony periodontal defects. J Periodont Res 47: 409-417.

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