February 13, 2011

L-PRF: Leukocytic Platelet Rich Fibrin – A New Frontier for Dentistry

Modern day alchemy has been used to describe the bone and tissue banks of the world today.  You remember alchemy, trying to turn something like lead into gold?  The bone/tissue banks don’t pay for their raw products, they instead get them from donors like you and me after we are dead, for free!  Then they turn it into products that they sell to dentists for the price equivalent of gold.  What a racket!  No wonder organized crime wants a piece of the action.

Bone morphogenetic proteins (BMP2) will not be widely available to dentistry any time soon as long as corporate greed exists in the world today.  One of my oral surgeons and I did one of those “Teeth in a Day” procedures to replace all of a patient’s maxillary teeth with a hybrid FPD, and just the costof the BMP2 alone was $5000 (bilateral sinus lift with facial onlay grafts and he was swollen like a toad, unable to wear his dentures for two weeks after).  After all, if they can sell BMP to an orthopedic surgeon for a big bucket of dollars, why should they sell a small dab to dentistry for a reasonable price ($800+ is the smallest amount they will sell to dentists).  I guess the thinking on this is that if they open up the market to the dental profession at a reasonable price, the orthopedic guys will just buy that instead of the high dollar product they currently are forced to buy.

Blood Clot

Platelet Rich Plasma (PRP) isn’t as expensive (or versatile) as BMP2, tissue, or bone, but the disposables used in the process of PRP amount to nearly the cost of bone products. Some of the PRP kits are fairly reasonable in price, but some border on being cost prohibitive.  Then there are always relatively cheap techniques like the one I was introduced to during an implant workshop out in L.A. by a periodontist named Jin Kim.

There has to be something out there that satisfies the many criteria for grafting/wound healing that modern dentistry can use without breaking the bank.  The patient populations around the world cannot routinely pay for processed bone, tissue, or even PRP at these prices.  Stacking the cost of these products on top of the cost of the extraction/implant/graft puts it out of reach for most people. Wouldn’t it be great if we had a material that was cheap, relatively easy to get, and completely compatible with every patient’s particular biological immunity? Also, a product that lasts up to 2 weeks in the body, super-charges the healing response, is a suturable membrane, can be placed in extraction site socket grafts, used with connective tissue grafts, and in sinus lift grafts?  Well, I think there is such a product out there that comes close, and it is going to change how dentists treat their every day patients around the world.

The product is called Leukocytic-Platelet Rich Fibrin (L-PRF) or just PRF for short. At first appearance, PRF sounds like PRP.  You still have to draw blood like PRP, and you still have to use a centrifuge like PRP, but that is were the similarities end.   Joseph Choukroun, MD, invented and pioneered the research and development of PRF membranes.

Fibrinogen is the active form of fibrin and is found in blood plasma.  It plays a role in platelet ?-granule aggregation during hemostasis.  Fibrinogen transforms into the insoluble sticky fibrin in the presence of the patient’s naturally occurring thrombin and consolidates the initial platelets into a clot at the site of an injury.  Not using foreign thrombin as in PRP it helps alleviate many fears over immune reactions and antigenicity problems that some fear may happen when using either bovine or human thrombin.

Trapping the platelets and leukocytes inside the fibrin clot helps in many ways:

  • Transforming Growth Factor beta or TGF? is a protein that assists in cellular differentiation and proliferation.
  • Platelet Derived Growth factor or PDGF helps bring in mesenchymal stem cells into the area as well as differentiate and proliferate endothelial cells.
  • Insulin-like Growth factor or IGF helps healing cells from dying so fast and continue healing longer.
  • Growth factors will work on type 1 collagen to form fibroblasts and osteoblasts
  • Releases cytokines to attract the healing response of the body.
  • Leukocytes will enhance the bodies own inflammatory process to heal quicker.
  • Fibrin network increase the blood flow into the area with Vascular Endothelial Growth Factor or VEGF.
  • Neutrophile degrades the site for wound remodeling and bring in the macrophages to clean up the site.

Making PRF from a patient’s blood is a very simple protocol: Blood is drawn without anticoagulant in 10-mL tubes.  It is immediately centrifuged at 2700 rpm for 12 minutes (or if they are on some kind of blood thinner then 18 minutes). Waiting more than a minute or two will cause the fibrin to polymerize in a diffuse way and only a small poorly formed clot will form in the test tube.  The trick is to start the process immediately after drawing the blood.  Doing it quickly, before the platelets can begin to coagulate from the trauma of the test tube/centrifuge process, will produce a very large PRF clot (approximately 40-60% of the product) in the middle of the test tube between the lighter clear platelet poor plasma and the packed red blood cells.  This PRF blood product is what is used to make this very resistant autologous fibrin membrane. It is then  lightly pressed to extract the growth factors used to rehydrate grafting materials.  It also can be used as a filler for bone grafts (sinus lifts/socket grafts) and as a healing membrane liner to accelerate the healing process up to two times faster.

The “kit” as it is sold from the Intra-Lock International company costs $3500 retail and $3000 at the meeting.  It comes with a centrifuge, two test tube racks, two boxes of test tubes, a tourniquet, a box of butterfly 23 gauge needles, two stainless processing boxes, two thin stainless bowls, 2 nice scissors and pick-up forceps, a little bag of fuses and other parts that I have no idea what they are for, an instruction manual obviously translated into English by someone from France, and a little bag of Band-Aids that looks like they were repackaged from a bigger box.  Unfortunately, this looks like another example of gouging the dental field.  They will not sell anyone the processing boxes without first buying their centrifuge.  We had one doctor there at the meeting that already secured a centrifuge over eBay for about $200, and was processing the PRF with “good” results.  However, the speaker strongly discouraged this process saying that the process was so delicate that you needed to only use their centrifuge or you may have different results.  That their centrifuge is weighted correctly, and is certified for this process.  Please make your own decisions about that…

All in all, the lecture on L-PRF was very good.  It brought up a lot of physiology I had not thought about in a long time. However, since this process is so new the speaker didn’t have a lot of definitive answers about how, and when it is to be used.  He would venture to say that others have used it in a certain way, only to recant by saying he didn’t do that because the literature didn’t support it, yet.

Case# 1

(This isn’t actually our first case.  We have done several socket grafts using the PRF membranes chopped up in the grafting material, and as a membrane for over the socket/under a cytoplast membrane.  We have also used it in through the crest sinus lifts).

This case was done at another office on a centrifuge that was so old it looked like the space viper probe droid that crashed onto the ice planet Hoth.  It had only one dial marked from 1 to 7 which indicated the speeds.  We had absolutely no idea what those speeds were. (International Equipment Co. NeedHam, Mass)

The patient was having a lateral wall sinus lift (metronidazole) with simultaneous implant placed under IV sedation and everyone there wanted to try to make some PRF for a surgical membrane to dress over the lateral window, and implant.  Two vials of blood were drawn, placed into the centrifuge, and dialed up to top speed, “7”.  The patient was on a low dose of coumadin so we spun it for 18 minutes. It worked!  The handling characteristics were similar to a wet paper towel laying on a table.  It didn’t want to attach to anything except the tissue it was placed over.  Very easy to manipulate. lateral window sinus liftsinus lift with implant PRF over lateral wall sinus lift windowPRF_sinus lift PRF final suture

This case in no way represents Dr. Choukroun’s research.  I have no idea if this fibrin clot has the same composition as a PRF clot done with the “officially calibrated” centrifuge sold by Intra-Lock.  If you have an old centrifuge and want to use it for the manufacturing of PRF, I suggest you experiment on a vial of your own blood first.  If you get a large well formed clot then congratulations.  If you cannot secure a “Box” to process a membrane, then try pressing the clot between two glass slabs.  The best and easiest way to make PRF for your patient is to contact Intra-Lock International and purchase the entire kit from them.

References:

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2. Rev Med Brux. 2010 Nov-Dec;31(6):521-7. [The use of platelet concentrates: platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in bone reconstruction prior to dental implant surgery]. [Article in French] Baeyens WGlineur REvrard L. Service de Stomatologie et de Chirurgie Maxillo-faciale, Hôpital Erasme, Bruxelles.

3. J Periodontol. 2011 Feb 2. [Epub ahead of print] Autologous Platelet Rich Fibrin in the Treatment of Mandibular Degree Ii Furcation Defects: A Randomized Clinical Trial. Pradeep ARSharma A. Department of Periodontics, Government Dental College and Research Institute, Bangalore-560002, Karnataka, INDIA.

4. Implant Dent. 2011 Feb;20(1):2-12. Simultaneous sinus-lift and implantation using microthreaded implants and leukocyte- and platelet-rich fibrin as sole grafting material: a six-year experience. Simonpieri AChoukroun JDel Corso MSammartino GDohan Ehrenfest DM. Department of Odontostomatological and Maxillofacial Sciences, University Federico II of Naples, Italy.

5. Cartilage. 2010 Oct;1(4):253-261. The Clinical Use of Human Culture-Expanded Autologous Bone Marrow Mesenchymal Stem Cells Transplanted on Platelet-Rich Fibrin Glue in the Treatment of Articular Cartilage Defects: A Pilot Study and Preliminary Results. Haleem AMSingergy AASabry DAtta HMRashed LAChu CREl Shewy MTAzzam AAbdel Aziz MT. Department of Orthopedic Surgery, Cairo University School of Medicine, Cairo, Egypt.

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14. J Trauma. 2011 Jan;70(1):228-37. Combination of guided osteogenesis with autologous platelet-rich fibrin glue and mesenchymal stem cell for mandibular reconstruction. Liao HTChen CTChen CHChen JPTsai JC. Division of Traumatic Plastic Surgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospitals, Chang Gung University College of Medicine, Taipei, Taiwan.

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17. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Sep;110(3):e8-14. Epub 2010 Jun 26. A comparison of bone generation capability in rabbits using tooth ash and plaster of Paris with platelet-rich plasma or fibrin sealant. Kim BKKim SGKim SYLim SCKim YK. Department of Oral and Maxillofacial Surgery, School of Dentistry, Chosun University, Gwangju, Korea.

18. Clin Oral Implants Res. 2010 May;21(5):543-9. Platelet-rich fibrin membranes as scaffolds for periosteal tissue engineering. Gassling VDouglas TWarnke PHAçil YWiltfang JBecker ST. Department of Oral and Maxillofacial Surgery, University of Schleswig-Holstein, Kiel, Germany. gassling@mkg.uni-kiel.de

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21. J Periodontol. 2010 Apr;81(4):546-55. Three-dimensional architecture and cell composition of a Choukroun’s platelet-rich fibrin clot and membrane. Dohan Ehrenfest DMDel Corso MDiss AMouhyi JCharrier JB. Department of Biomaterials, Institute for Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 8B, 41390 Gothenburg, Sweden. lob5@mac.com

22. J Cosmet Dermatol. 2010 Mar;9(1):66-71. Platelet-rich fibrin matrix for improvement of deep nasolabial folds. Sclafani AP. Division of Facial Plastic Surgery, The New York Eye & Ear Infirmary, New York, New York 10003, USA. asclafani@nyee.edu

23. Arch Oral Biol. 2010 Mar;55(3):185-94. Epub 2010 Feb 21. Choukroun’s platelet-rich fibrin (PRF) stimulates in vitro proliferation and differentiation of human oral bone mesenchymal stem cell in a dose-dependent way. Dohan Ehrenfest DMDoglioli Pde Peppo GMDel Corso MCharrier JB. Department of Biomaterials, Institute for Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Sweden. LoB5@mac.com

24. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Jun;109(6):831-6. Epub 2010 Feb 16. Restoration of peri-implant defects in immediate implant installations by Choukroun platelet-rich fibrin and silk fibroin powder combination graft. Jang ESPark JWKweon HLee KGKang SWBaek DHChoi JYKim SG. Department of Oral and Maxillofacial Surgery, Hallym University, Kyoungkido, Korea.

25. J Foot Ankle Surg. 2010 Mar-Apr;49(2):128-34. Epub 2010 Feb 4. Comparison of Achilles tendon repair techniques in a sheep model using a cross-linked acellular porcine dermal patch and platelet-rich plasma fibrin matrix for augmentation. Sarrafian TLWang HHackett ESYao JQShih MSRamsay HLTurner AS. Colorado State University, Veterinary Medical Center, Fort Collins, CO, USA.

26. J Periodontol. 2009 Dec;80(12):2056-64. 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. Mazor ZHorowitz RADel Corso MPrasad HSRohrer MDDohan Ehrenfest DM. Private Practice, Ra’anana, Israel.

27. Facial Plast Surg. 2009 Nov;25(4):270-6. Epub 2009 Nov 18. Applications of platelet-rich fibrin matrix in facial plastic surgery. Sclafani AP. Director of Facial Plastic Surgery, The New York Eye and Ear Infirmary, New York, New York 10003, USA.

28. J Periodontol. 2009 Nov;80(11):1694-7; author reply 1697-9. Re: “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”. Del Corso MSammartino GDohan Ehrenfest DM.

29. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Nov;108(5):707-13. A comparative study of platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) on the effect of proliferation and differentiation of rat osteoblasts in vitro. He LLin YHu XZhang YWu H. Department of Implantology, School and Hospital of Stomatology, Peking University, Beijing, China.

3o. Transfusion. 2010 Feb;50(2):501-6. Epub 2009 Oct 9. Platelet gel for treatment of mucocutaneous lesions related to graft-versus-host disease after allogeneic hematopoietic stem cell transplant. Picardi ALanti ACudillo LCerretti RDentamaro TDe Angelis GFerraro ADi Veroli AAdorno GArcese WRome Transplant Network. Department of Haematology, Stem Cell Transplant Unit, Policlinico Tor Vergata, Rome, Italy. picardi@med.uniroma2.it

31. Biologicals. 2010 Jan;38(1):120-7. Epub 2009 Aug 31. Influence of ethanol on the release of growth factors in human blood-derived platelet gels. Kuo YPLee YLTseng YHSu CHBurnouf TSu CY. Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.

32. Eur Surg Res. 2009;43(3):306-9. Epub 2009 Aug 13. Mesh fixation with autologous platelet-rich fibrin sealant in inguinal hernia repair. de Hingh IHNienhuijs SWOverdevest EPScheele KEverts PA. Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.

33. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Sep;108(3):341-52. Epub 2009 Jul 9. In vitro effects of Choukroun’s PRF (platelet-rich fibrin) on human gingival fibroblasts, dermal prekeratinocytes, preadipocytes, and maxillofacial osteoblasts in primary cultures. Dohan Ehrenfest DMDiss AOdin GDoglioli PHippolyte MPCharrier JB. Researcher, Department of Biomaterials, Institute for Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. LoB5@mac.com

34. Open Dent J. 2009 May 20;3:92-99. Clinical and Histological Comparison of Extraction Socket Healing Following the Use of Autologous Platelet-Rich Fibrin Matrix (PRFM) to Ridge Preservation Procedures Employing Demineralized Freeze Dried Bone Allograft Material and Membrane. Simon BIZatcoff ALKong JJO’Connell SM. New Jersey Dental School, USA.

35. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Jul;108(1):48-55. Epub 2009 May 17. Platelet-rich plasma and platelet-rich fibrin in human cell culture. Gassling VLAçil YSpringer INHubert NWiltfang J. Department of Oral and Maxillofacial Surgery, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany. gassling@mkg.uni-kiel.de

36. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Jul;108(1):56-61. Epub 2009 May 17. In vitro release of growth factors from platelet-rich fibrin (PRF): a proposal to optimize the clinical applications of PRF. Su CYKuo YPTseng YHSu CHBurnouf T. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan. henrycysu@gmail.com

37. Sports Med. 2009;39(5):345-54. doi: 10.2165/00007256-200939050-00002. Platelet-rich therapies in the treatment of orthopaedic sport injuries. Sánchez MAnitua EOrive GMujika IAndia I. Unidad de Cirugía Artroscópica “Mikel Sánchez”, La Esperanza, Vitoria, Spain.

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39. Rev Stomatol Chir Maxillofac. 2009 Apr;110(2):105-8. Epub 2009 Mar 26. [Solitary bone cyst of the mandible and platelet rich fibrin (PRF)]. [Article in French] Magremanne MBaeyens WAwada SVervaet C. Service de stomatologie et chirurgie maxillofaciale, hôpital Erasme, université Libre de Bruxelles, 808, route de Lennik, 1070 Bruxelles, Belgique. magremanne.michele@gmail.com

40. Trends Biotechnol. 2009 Mar;27(3):158-67. Epub 2009 Jan 31. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Dohan Ehrenfest DMRasmusson LAlbrektsson T. Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Sweden. LoB5@mac.com

41. J Periodontol. 2009 Feb;80(2):244-52. 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. Aroca SKeglevich TBarbieri BGera IEtienne D. sofiaaroca@mac.com

42. Wound Repair Regen. 2008 Nov-Dec;16(6):749-56. Autologous platelet-rich fibrin matrix as cell therapy in the healing of chronic lower-extremity ulcers. O’Connell SMImpeduglia THessler KWang XJCarroll RJDardik H. Department of Vascular Surgery, Englewood Hospital and Medical Center, Mount Sinai School of Medicine, Englewood, New Jersey, USA.

43. J Indian Soc Periodontol. 2009 Jan;13(1):50-4. Platelet-rich-fibrin: A novel root coverage approach. Anilkumar KGeetha AUmasudhakarRamakrishnan TVijayalakshmi RPameela E. Lecturer, Department of Periodontics, Meenakshi Ammal Dental College, Madhuravoyal, Chennai – 600 095, India.

44. Rev Laryngol Otol Rhinol (Bord). 2009;130(3):175-80. [The relevance of Choukroun’s Platelet-Rich Fibrin (PRF) during middle ear surgery: preliminary results]. [Article in French] Braccini FTardivet LDohan Ehrenfest DM. Institut Azuréen d’ORL et de Chirurgie de la Face, 25 Avenue Jean Médecin, F-06000 Nice, France. contact@braccini.net

45. Growth Factors. 2009 Feb;27(1):63-9. Slow release of growth factors and thrombospondin-1 in Choukroun’s platelet-rich fibrin (PRF): a gold standard to achieve for all surgical platelet concentrates technologies. Dohan Ehrenfest DMde Peppo GMDoglioli PSammartino G. Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. LoB5@mac.com

46. J Orthop Res. 2009 Jul;27(7):972-80. Activated platelets increase fibrinolysis of mesenchymal progenitor cells. Agis HKandler BFischer MBWatzek GGruber R. Department of Oral Surgery, Medical University of Vienna, Währingerstrasse 25a, 1090 Vienna, Austria.

47. J Tissue Eng Regen Med. 2008 Dec;2(8):515-20. Use of autologous bone marrow cells concentrate enriched with platelet-rich fibrin on corticocancellous bone allograft for posterolateral multilevel cervical fusion. Vadalà GDi Martino ATirindelli MCDenaro LDenaro V. Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Rome, Italy.

48. Plast Reconstr Surg. 2008 Nov;122(5):1431-40. Effect of topical autologous platelet-rich fibrin versus no intervention on epithelialization of donor sites and meshed split-thickness skin autografts: a randomized clinical trial. Danielsen PJørgensen BKarlsmark TJorgensen LNAgren MS. Department of Surgery K and the Copenhagen Wound Healing Center, Bispebjerg University Hospital, Copenhagen, Denmark.

49. J Wound Care. 2008 Feb;17(2):60-3. Use of autologous platelet-rich fibrin on hard-to-heal wounds. Steenvoorde Pvan Doorn LPNaves COskam J. I Department of Surgery, Rijnland Hospital, Leiderdorp, The Netherlands. psteenvoorde@zonnet.nl

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51. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 May;105(5):572-9. Epub 2008 Mar 4. Osteotome sinus floor elevation using Choukroun’s platelet-rich fibrin as grafting material: a 1-year prospective pilot study with microthreaded implants. Diss ADohan DMMouhyi JMahler P. LASIO, Odontology Faculty, Nice University, France.

52. Wound Repair Regen. 2008 May-Jun;16(3):356-63. Epub 2008 Feb 13. Bioactivity and stability of endogenous fibrogenic factors in platelet-rich fibrin. Lundquist RDziegiel MHAgren MS. Department of Surgery K, Bispebjerg Hospital, Copenhagen, Denmark.

53. Indian J Dent Res. 2008 Jan-Mar;19(1):42-6. Platelet-rich fibrin: evolution of a second-generation platelet concentrate. Sunitha Raja VMunirathnam Naidu E. Department of Periodontics, Meenakshiammal Dental College and Hospital, Maduravoyal, Chennai, India. sunitha.smiles@yahoo.com

54. Rev Laryngol Otol Rhinol (Bord). 2008;129(4-5):313-8. Relevance of Choukroun’s Platelet-Rich Fibrin (PRF) and SMAS flap in primary reconstruction after superficial or subtotal parotidectomy in patients with focal pleiomorphic adenoma: a new technique. Charrier JBMonteil JPAlbert SCollon SBobin SDohan Ehrenfest DM. AP-HP Bicêtre Hospital, Department of Head and Neck Surgery, Université Paris Sud-11, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France. jean-baptiste.charrier@bct.aphp.fr

55. J Oral Implantol. 2007;33(4):205-10. Minimally invasive guided bone regeneration. Kfir EKfir VEliav EKaluski E. Department of Dentistry, University Hospital, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, MSB, Room 1-538, Newark, NJ 07101, USA.

56. Rev Laryngol Otol Rhinol (Bord). 2007;128(1-2):27-32. [Influence of platelet rich fibrin (PRF) on proliferation of human preadipocytes and tympanic keratinocytes: A new opportunity in facial lipostructure (Coleman’s technique) and tympanoplasty?]. [Article in French] Choukroun JIBraccini FDiss AGiordano GDoglioli PDohan DM. Centre Anti-Douleur, 49 Rue Gioffredo, 06000 Nice, France. joseph.choukroun@free.fr

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