Platelet rich fibrin: an autologous bioactive membrane

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Platelet-Rich Fibrin (PRF) is a new second-generation platelet concentrate, with simplified processing, and no biochemical blood handling. It has several advantages over traditionally prepared PRP, which has been widely used for accelerating soft tissue and hard tissue healing for years. Strictly autologous preparation, the amount of PRF obtained is limited, includes its disadvantages. Choukroun’s PRF incorporates leucocytes, platelets and a wide range of healing proteins within a dense fibrin matrix. It is a natural bioactive membrane, which can enhance soft/hard tissue healing, at the same time, can also protect surgical sites, grafted materials from external aggressions. This article describes the evolution of this second-generation platelet concentrate and its multiple uses in various surgical procedures.

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Platelet rich fibrin: an autologous bioactive membrane

  1. 1. Platelet rich fibrin: an autologous bioactive membrane
  2. 2. Review Article Platelet rich fibrin: an autologous bioactive membrane Anirban Chatterjee a, *, Prerna Agarwal b , Shobha Krishna Subbaiah b a Sr. Consultant, Periodontist & Implantologyst, Apollo Hospital, Bangalore 560038, India b Consultant, Periodontist, Apollo Clinic, Bangalore 560038, India a r t i c l e i n f o Article history: Received 26 December 2013 Accepted 30 January 2014 Available online 12 March 2014 Keywords: PRF PRP Growth factors a b s t r a c t Platelet-Rich Fibrin (PRF) is a new second-generation platelet concentrate, with simplified processing, and no biochemical blood handling. It has several advantages over traditionally prepared PRP, which has been widely used for accelerating soft tissue and hard tissue healing for years. Strictly autologous preparation, the amount of PRF obtained is limited, includes its disadvantages. Choukroun’s PRF incorporates leucocytes, platelets and a wide range of healing proteins within a dense fibrin matrix. It is a natural bioactive membrane, which can enhance soft/hard tissue healing, at the same time, can also protect surgical sites, grafted materials from external aggressions. This article describes the evolution of this second-generation platelet concentrate and its multiple uses in various surgical procedures. Copyright ª 2014, Indraprastha Medical Corporation Ltd. All rights reserved. 1. Introduction Regenerative potential of platelets was introduced in 1974, and Ross et al1 were amongst the pioneers who first described a growth factor from platelets. A new family of platelet concentrate, which is neither a fibrin glue nor a classical platelet concentrate, discovered in France because of legal complications of biochemical blood handling. This new biomaterial is called as PRF, looks like an autologous cicatricial matrix.2 PRF is a fibrin matrix of trapped platelets, cytokines and other cells, which are released after a certain time,3 to act as a resorbable biomembrane. More recently, Gassling et al4 have shown that PRF is a suitable scaffold for breeding human periosteal cells in vitro, which may be suitable for bone tissue engineering applications.5 2. What is fibrin? Fibrin is the activated form of a plasmatic molecule called fibrinogen.6 This soluble fibrillary molecule is massively present both in plasma and in the platelet a-granules and plays a determining role in platelet aggregation during he- mostasis. It is transformed into a kind of biologic glue capable of consolidating the initial platelet cluster, thus constituting a protective wall along vascular breaches dur- ing coagulation. In fact, fibrinogen is the final substrate of all coagulation reactions. Being a soluble protein, fibrinogen is transformed into an insoluble fibrin by thrombin while the polymerized fibrin gel constitutes the first cicatricial matrix of the injured site.7e9 * Corresponding author. Tel.: þ91 9845003721. E-mail address: dranirbanchatterjee@yahoo.com (A. Chatterjee). Available online at www.sciencedirect.com ScienceDirect journal homepage: www.elsevier.com/locate/apme a p o l l o m e d i c i n e 1 1 ( 2 0 1 4 ) 2 4 e2 6 http://dx.doi.org/10.1016/j.apme.2014.01.007 0976-0016/Copyright ª 2014, Indraprastha Medical Corporation Ltd. All rights reserved.
  3. 3. 3. Biological aspect PRF was developed in France by Choukroun et al10 Basically the platelets and released cytokines are accumulated in a fibrin clot. Platelet granules contain many platelet specific (eg. beta-thromboglobulins) & non-platelet specific proteins (eg. fibronectin, thrombospondin, fibrinogen, growth promoters, fibrinolysis inhibitors, immunoglobulins etc), calcium and serotonin etc.11 Growth factors released by alpha-granules encompass a group of cytokine polypeptides with relatively low molecular weight ranging from 6 to 45 kDa.12 After acti- vation and degranulation platelets aggregates at the healing site and release the cytokines (IL-1 beta, IL-6, tumor necrosis factor (TNF)-alpha)13 and growth factors (transforming growth factor (TGF) beta 1, platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF)) that stimulates cell migration and proliferation within the fibrin matrix and thus begins the first stage of healing.11 According to Dohan et al13 PRF may decreases many harmful effects at inflammatory site natural to surgical act and thus could be an immune regulation node with inflam- mation retro-control abilities and explained the reduction of post-operative infections. 4. Platelet-rich fibrinda natural fibrin matrix Platelet-rich fibrin (PRF) requires neither anticoagulant nor bovine thrombin (nor any other gelling agent). It is nothing more than centrifuged blood without any addition, which makes it possible to avoid all the restrictions. The PRF protocol is very simple: A blood sample is taken without anticoagulant & immediately centrifuged at 3000 rpm for 10 min. Due to the absence of anticoagulant, most of the platelets activates within few minutes and release the coagulation cascades. Acellular plasma is initially accumulated in the upper part of the tube, before the circulating thrombin transforms it into fibrin. A fibrin clot is then obtained in the middle of the tube, just between the red corpuscles at the bottom and acellular plasma at the top (Fig. 1).2 Quick handling is the only way to obtain a clinically usable PRF clot. If the duration required to collect blood and launch centrifugation is overly long, failure will occur: The fibrin will polymerize in a diffuse way in the tube and only a small blood clot without consistency will be obtained. In conclusion, the PRF protocol makes it possible to collect a fibrin clot charged with serum and platelets. By driving out the fluids trapped in the fibrin matrix, practitioners will obtain very resistant autologous fibrin membranes.2,10 5. Clinical implications Choukroun et al10 were amongst the pioneers for using autologous PRF to improve bone healing in implant dentistry. They evaluate the potential of PRF in combination with freeze- dried bone allograft (FDBA) to enhance bone regeneration in sinus floor elevation and sinus floor augmentation. In their study, PRF was added to FDBA particles (test group), and FDBA without PRF was used (control group). In results they found, the maturation & quantities of newly formed bone were equivalent between the two groups.14 Mazor et al15 assessed the relevance of PRF concentrate and biomembranes as the sole filling material during a lateral sinus lift with immediate implantation in a case series. From a radiologic and histo- logical point of view at 6 months after surgery, they found a high volume of regenerated bone in the subsinus cavity up to the tip of the implants. Toffler et al16 advocated membrane insurance by possibly sealing an undetected perforation dur- ing lateral window osteotomy procedure using PRF mem- brane. In a multicenteric study by Kfir et al,17 minimally invasive antral membrane balloon elevation (MIAMBE) done using PRF and bone substitutes, injected under the antral membrane and implant placement along with primary closure executed at the same sitting, revealed that MIAMBE can be applied to all patients in need of posterior maxilla bone augmentation with high procedural success, low complication rate, and satisfactory bone augmentation and implant sur- vival. Simonpieri et al18,19 reported maxillary reconstruction using FDBA, PRF membranes and 0.5% metronidazole solution in twenty patients case series. Toffler20 advocated osteotome- mediated sinus floor elevation (OMSFE) or crestal core eleva- tion (CCE)21 with simultaneous implant placement using PRF plugs. Thick PRF plugs or small disks of 1 cm diameter can also be easily inserted into the residual extraction sockets.16 Aroca et al22 evaluate the modified coronally advanced flap alone or in combination with PRF for the treatment of adjacent Miller Class I and II multiple gingival recession, & discovered inferior root coverage of about 80.7% as compared to about 91.5% achieved at control site, but an additional gain in gingival/ mucosal thickness compared to conventional therapy. 6. Conclusion Thus, with this article we can conclude that the new and recent generation of platelet concentrate-PRF, would be a good friend to Periodontists in the near future. It has a list of its benefits, & intraoral applications. This material is already being used widely in France, and considering its advantages, its popularity should increase here too. More clinical, histo- logical and statistical studies are now required to understandFig. 1 e Different layers after blood centrifugation. a p o l l o m e d i c i n e 1 1 ( 2 0 1 4 ) 2 4 e2 6 25
  4. 4. the benefits of this new platelet concentrate better. However, it cannot be ignored that since it is obtained from an autolo- gous blood sample, the quantity of PRF produced is low and only a limited volume can be used. This fact limits the sys- tematic utilization of PRF, as in general surgery. Also though the potential applications of PRF are broad, however, an ac- curate working knowledge of the biomaterial, its biology, ef- ficiency & limits are necessary to optimize its use in daily practice. Hence additional randomized clinical trials evalu- ating the use & performance of PRF are warranted. Conflicts of interest All authors have none to declare. r e f e r e n c e s 1. Ross R, Glomset J, Kariya B, Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci U S A. 1974;71:1207e1210. 2. 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:e37ee44. 3. Mosesson MW. Fibrinogen and fibrin structure and functions. J Thromb Haemost. 2005;3:1894e1904. 4. Gassling V, Douglas T, Warnke YA, Wiltfang J, Becker ST. Platelet-rich fibrin membranes as scaffolds for periosteal tissue engineering. Clin Oral Impl. 2010;21:543e549. 5. Anitua E, Sa´nchez M, Nurden AT, Nurden P, Orive G, Andı´a I. New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol. 2006;24:227e234. 6. Mosesson MW, Siebenlist KR, Meh DA. The structure and biological features of fibrinogen and fibrin. Ann N YAcad Sci. 2001;936:11e30. 7. Clark RA. Fibrin and wound healing. Ann N Y Acad Sci. 2001;936:355e367. 8. Collen A, Koolwijk P, Kroon M, van Hinsbergh VW. Influence of fibrin structure on the formation and maintenance of capillary like tubules by human microvascular endothelial cells. Angiogenesis. 1998;2:153e165. 9. van Hinsbergh VW, Collen A, Koolwijk P. Role of fibrin matrix in angiogenesis. Ann N Y Acad Sci. 2001;936:426e437. 10. Choukroun J, Adda F, Schoeffler C, Vervelle A. Une opportunite´ en paro-implantologie: le PRF. Implantodontie. 2001;42:55e62. 11. Dohan DM, Choukroun J, Diss A, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:e45ee50. 12. Su CY, Kuo YP, Tseng YH, Su CH, Burnouf T. In vitro release of growth factors from platelet-rich fibrin (PRF): a proposal to optimize the clinical applications of PRF. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108:56e61. 13. 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:e51ee55. 14. Choukroun J, Diss A, Simonpieri A, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part V: histologic evaluations of PRF effects on bone allograft maturation in sinus lift. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:299e303. 15. 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;80:2056e2064. 16. 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 Adv Clin Dent. 2009;1:21e30. 17. Kfir E, Goldstein M, Yerushalmi I, et al. Minimally invasive antral membrane balloon elevation e results of a multicenter registry. Clin Implant Dent Relat Res. 2009;11(suppl 1):e83ee91. 18. Simonpieri A, Del Corso M, Sammartino G, Dohan Ehrenfest DM. The relevance of Choukroun’s platelet-rich fibrin and metronidazole during complex maxillary rehabilitations using bone allograft. Part I: a new grafting protocol. Implant Dent. 2009;18:102e111. 19. Simonpieri A, Del Corso M, Sammartino G, Dohan Ehrenfest DM. The relevance of Choukroun’s platelet-rich fibrin and metronidazole during complex maxillary rehabilitations using bone allograft. Part II: implant surgery, prosthodontics, and survival. Implant Dent. 2009;18:220e229. 20. Toffler M. Osteotome-mediated sinus floor elevation: a clinical report. Int J Oral Maxillofac Implants. 2004;19:266e273. 21. Toffler M. Staged sinus augmentation using a crestal core elevation procedure (CCE) to minimize membrane perforation. Pract Proced Aesthet Dent. 2002;14:767e774. 22. Aroca S, Keglevich T, Barbieri B, Gera I, Etienne D. Clinical evaluation of a modified coronally advanced flap alone or in combination with a platelet-rich fibrin membrane for the treatment of adjacent multiple gingival recessions: a 6-month study. J Periodontol. 2009;80:244e252. a p o l l o m e d i c i n e 1 1 ( 2 0 1 4 ) 2 4 e2 626
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