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Compendium
September 2020
Volume 41, Issue 8

Platelet-Rich Fibrin: Choosing the Right Formulation for Optimal Results

Andrew T. Moshman, DMD

Autologous blood concentrates are rich sources of bioactive molecules derived from a patient's own blood that have gained popularity for their use in medical and dental procedures.1 The introduction of high concentrations of platelets and growth factors to surgical sites speeds hard- and soft-tissue healing and helps achieve positive, predictable treatment outcomes.2 One such concentrate, platelet-rich fibrin (PRF), has broad applications in dentistry, but a vast array of product variations can make it difficult for clinicians to know whether they are utilizing the most optimal PRF protocol and corresponding centrifuge.

The first-generation blood platelet concentrate, platelet-rich plasma (PRP), was initially reported used in oral surgery procedures in 1997.3 Following venous blood draw, whole blood is treated with an anticoagulant (usually sodium citrate or anticoagulant citrate dextrose solution A) and undergoes two centrifugation steps.4 The centrifuge separates the individual cell types found in whole blood between separate layers (platelet-poor plasma, PRP, red blood cell layer), which can then be used during treatment. A separate platelet activator/agonist (bovine thrombin and calcium chloride) must be applied just before clinical use.5 Although PRP is an autologous biomaterial, the anticoagulant has been shown to compromise wound healing,6 while the coagulant may trigger antibody development to factors V, XI, and thrombin, possibly leading to life-threatening coagulopathies.7,8

In 2001 Choukroun introduced the second-generation blood platelet concentrate, platelet-rich fibrin (L-PRF).9 Because PRF is derived from a patient's own blood without the use of anticoagulants, there is no risk of immunologic rejection. After centrifugation, three layers are present: platelet-poor plasma, the PRF clot, and red blood cell layer. A "buffy coat" layer is located at the base of the PRF clot, just above the red corpuscle layer. While the terms "autologous blood concentrate" and "blood platelet concentrate" can be used to describe both PRP and PRF, PRF also contains concentrations of leukocytes (white blood cells), which are not present in PRP.10 White blood cells provide the additional benefits of increased immune response, angiogenesis, and promotion of hard-tissue formation at surgical sites.11,12 PRF has been shown to contain CD34+ stem cells that are found in peripheral blood13 and which aid in the process of tissue regeneration.14 The fibrin matrix serves as a scaffold and contains rich concentrations of platelets, growth factors, and leukocytes. The solid PRF clot exists in a thick, gel-like state and can be compressed into a flat membrane or a plug as desired for optimal utilization during treatment. The fibrin matrix may act as a cell-occlusive barrier against soft-tissue invagination into surgical sites.2,15

While PRP rapidly releases more than 90% of its growth factors within 10 minutes of coagulation and depletes the remainder within 90 minutes,16 PRF, conversely, has a prolonged release (beyond 7 days) of growth factors and, moreover, has been shown to release a higher overall number of growth factors.17 Prolonged release is beneficial, as the process of tissue repair and remodeling lasts for months.

PRF is often used in periodontology and oral and maxillofacial surgery for hard- and soft-tissue augmentation, bone grafting, sinus augmentation, and implantology. PRF has also been utilized in endodontics for regenerative endodontic therapy as well as endodontic surgery.18 While many clinicians are aware of PRF, the differences among PRF formulations can be perplexing. Furthermore, for commercial reasons the names of many PRF protocols have been trademarked and are associated with a particular centrifuge device.19 Since the introduction of PRF two decades ago, numerous fixed-angle centrifuges and alterations to the centrifugation protocols have produced varying forms of PRF, including leukocyte-rich PRF (L-PRF), advanced PRF (A-PRF), liquid injectable PRF (i-PRF), and advanced PRF Plus (A-PRF+).9,10,20-22 A trend has been towards lower g-forces and/or shorter centrifugation time, resulting in higher concentrations of platelets, leukocytes, and growth factors.21,22

Concentrated PRF (C-PRF) was recently developed by using the L-PRF protocol and extracting only liquid contents from within the small buffy coat layer.23 C-PRF produces very high concentrations of leukocytes and platelets, and C-PRF has been shown to be superior to i-PRF in terms of platelet and leukocyte concentration and growth factor release.24

In 2018 Lourenço et al introduced horizontal centrifugation as a method to produce PRF.25 A commercial PRF produced via horizontal centrifugation is known as Bio-PRF.

Lowering the relative centrifugation force can produce a liquid PRF, consisting of liquid fibrinogen.21 Three different liquid PRF formulations are i-PRF (fixed-angle centrifuge), C-PRF (fixed-angle centrifuge), and Bio-PRF liquid (horizontal centrifuge). The liquid PRF coagulates over the course of several minutes, and when combined with graft particulate such as allograft it congeals into a solid mass that allows for improved handling, manipulation, and placement into a surgical site; this is referred to as "sticky bone."26 Sticky bone combines the osteoconductive and scaffolding properties of the allograft with the high concentrations of platelets, leukocytes, and growth factors found in PRF. One direct study shows higher concentrations of bioactive cells and growth factors in C-PRF compared to i-PRF24; to date C-PRF has not been compared to Bio-PRF liquid.

With so much variation among PRF names and centrifuges, it can be challenging for dentists to choose which centrifuge is ideal for their clinical practice. Centrifuge devices can usually be programmed to follow other protocols not associated with their particular trademarked PRF.

In 2019 Miron et al compared cell concentrations among liquid PRF and solid PRF produced on three different centrifuge devices and found that among the protocols tested, the highest concentrations of platelets and leukocytes were found in solid and liquid PRF made using horizontal centrifugation.27 Liquid PRF produced via horizontal centrifugation, in particular, contained the highest overall concentrations of both leukocytes and platelets. These findings indicate that PRF produced using a horizontal centrifuge is superior to that made from a fixed-angle centrifuge. Additionally, the authors advised against the use of the solid L-PRF protocol for membrane fabrication due to an uneven distribution of cells, which are located only at the base of the PRF clot.27 The authors also found that the liquid A-PRF protocol did not achieve adequate separation of cell types and failed to produce high quantities of platelets or leukocytes.

Finally, another PRF derivative, concentrated growth factor (CGF), was developed by Sacco using a fixed-angle centrifuge.28 Despite different centrifuges and protocols, CGF is identical to PRF in terms of mechanical and degradable properties.29 To date, no studies have compared cell or growth factor concentrations between CGF, C-PRF, and Bio-PRF.

The properties and uses of PRF, as well as their formulations that are available commercially, are wide-ranging in dentistry. Clinicians can benefit from knowing and understanding the differences among the many PRF products that may be used to promote bone and soft-tissue healing and regeneration.

About the Author

Andrew T. Moshman, DMD
Private Practice, Brooklyn, New York

Disclosure

The author had no disclosures to report.

References

1. Saini K, Chopra P, Sheokand V. Journey of platelet concentrates: a review. Biomed Pharmacol J. 2020;13(1):185-191.

2. Borie E, Oliví DG, Orsi IA, et al. Platelet-rich fibrin application in dentistry: a literature review. Int J Clin Exp Med.2015;8(5):7922-7929.

3. Whitman DH, Berry RL, Green DM. Platelet gel: an alternative to fibrin glue with applications in oral and maxillofacial surgery. J Oral Maxillofac Surg. 1997;55(11):1294-1299.

4. do Amaral RJ, da Silva NP, Haddad NF, et al. Platelet-rich plasma obtained with different anticoagulants and their effect on platelet numbers and mesenchymal stromal cells behavior in vitro. Stem Cells Int. 2016;2016:7414036. doi: 10.1155/2016/7414036.

5. Wang HL, Avila G. Platelet rich plasma: myth or reality? Eur J Dent. 2007;1(4):192-194.

6. Oneto P, Zubiry PR, Schattner M, Etulain J. Anticoagulants interfere with the angiogenic and regenerative responses mediated by platelets. Front Bioeng Biotechnol. 2020;8:223. doi: 10.3389/fbioe.2020.00223.

7. Kiran NK, Mukunda KS, Tilak Raj TN. Platelet concentrates: a promising innovation in dentistry. J Dent Sci Res. 2011;2(1):50-61.

8. Landesberg R, Moses M, Karpatkin M. Risks of using platelet rich plasma gel. J Oral Maxillofac Surg. 1998;56(9):1116-1117.

9. Dohan DM, Choukroun J, Diss A, 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(3):e37-e44.

10. Choukroun J. Advanced PRF and i-PRF: platelet concentrates or blood concentrates? J Periodont Med Clin Pract. 2014;1.

11. Dohan DM, Choukroun J, Diss A, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates? Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):e51-e55.

12. Choukroun J, Diss A, Simonpieri A, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part IV: clinical effects on tissue healing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):e56-e60.

13. Di Liddo R, Bertalot T, Borean A, et al. Leucocyte and platelet-rich fibrin: a carrier of autologous multipotent cells for regenerative medicine. J Cell Mol Med. 2018;22(3):1840-1854.

14. Caloprisco G, Borean A, De Angeli S, et al. New method to produce hemocomponents for regenerative use from peripheral blood: integration among platelet growth factors monocytes and stem cells. Transfus Apher Sci. 2010;42(2):117-124.

15. Clark D, Rajendran Y, Paydar S, et al. Advanced platelet-rich fibrin and freeze-dried bone allograft for ridge preservation: a randomized controlled clinical trial. J Periodontol. 2018;89(4):379-387.

16. Misch CE. Contemporary Implant Dentistry. 3rd ed. St. Louis, MO: Mosby Elsevier; 2007.

17. Ehrenfest DMD, Bielecki T, Jimbo R, et al. Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF). Curr Pharm Biotechnol. 2012;13(7):1145-1152.

18. Sabeti M, Lee ES, Torabinejad M. PRF Applications in Endodontics. Batavia, IL: Quintessence Publishing; 2020.

19. Kawase T, Tanaka T. An updated proposal for terminology and classification of platelet-rich fibrin. Regen Ther. 2017;7:80-81.

20. Ghanaati S, Booms P, Orlowska A, et al. Advanced platelet-rich fibrin: a new concept for cell-based tissue engineering by means of inflammatory cells. J Oral Implantol.2014;40(6):679-689.

21. Choukroun J, Ghanaati S. Reduction of relative centrifugation force within injectable platelet-rich-fibrin (PRF) concentrates advances patients' own inflammatory cells, platelets and growth factors: the first introduction to the low speed centrifugation concept. Eur J Trauma Emerg Surg. 2018;44(1):87-95.

22. Fujioka-Kobayashi M, Miron RJ, Hernandez M, et al. Optimized platelet-rich fibrin with the low-speed concept: growth factor release, biocompatibility, and cellular response. J Periodontol. 2017;88(1):112-121.

23. Miron RJ, Chai J, Zhang P, et al. A novel method for harvesting concentrated platelet-rich fibrin (C-PRF) with a 10-fold increase in platelet and leukocyte yields. Clin Oral Investig. 2020;24(8):2819-2828.

24. Fujioka-Kobayashi M, Katagiri H, Kono M, et al. Improved growth factor delivery and cellular activity using concentrated platelet-rich fibrin (C-PRF) when compared with traditional injectable (i-PRF) protocols. Clin Oral Investig. 2020; doi: 10.1007/s00784-020-03303-7.

25. Lourenço ES, de Almeida Barros Mourão CF, Corrêa Leite PE, et al. The in vitro release of cytokines and growth factors from fibrin membranes produced through horizontal centrifugation. J Biomed Mater Res A. 2018;106(5):1373-1380.

26. de Almeida Barros Mourão CF, Valiense H, Melo ER, et al. Obtention of injectable platelets rich-fibrin (i-PRF) and its polymerization with bone graft: technical note. Rev Col Bras Cir. 2015;42(6):421-423.

27. Miron RJ, Chai J, Zheng S, et al. A novel method for evaluating and quantifying cell types in platelet rich fibrin and an introduction to horizontal centrifugation. J Biomed Mater Res A. 2019;107(10):2257-2271.

28. Bernardi S, Tecco S, Mummolo S, Continenza MA. Histological characterization of Sacco's concentrated growth factors membrane. Int J Morphol. 2017;35(1):114-119.

29. Isobe K, Watanebe T, Kawabata H, et al. Mechanical and degradation properties of advanced platelet-rich fibrin (A-PRF), concentrated growth factors (CGF), and platelet-poor plasma-derived fibrin (PPTF). Int J Implant Dent. 2017;3(1):17.

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