Skip to main content

Advertisement

SpringerLink
Log in

Injectable platelet rich fibrin (i-PRF): opportunities in regenerative dentistry?

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

Platelet rich plasma (PRP) has been utilized in regenerative dentistry as a supra-physiological concentrate of autologous growth factors capable of stimulating tissue regeneration. Despite this, concerns have been expressed regarding the use of anti-coagulants, agents known to inhibit wound healing. In this study, a liquid formulation of platelet rich fibrin (PRF) termed injectable-PRF (i-PRF) without the use of anti-coagulants was investigated.

Materials and methods

Standard PRP and i-PRF (centrifuged at 700 rpm (60G) for 3 min) were compared for growth factor release up to 10 days (8 donor samples). Furthermore, fibroblast biocompatibility at 24 h (live/dead assay); migration at 24 h; proliferation at 1, 3, and 5 days, and expression of PDGF, TGF-β, and collagen1 at 3 and 7 days were investigated.

Results

Growth factor release demonstrated that in general PRP had higher early release of growth factors whereas i-PRF showed significantly higher levels of total long-term release of PDGF-AA, PDGF-AB, EGF, and IGF-1 after 10 days. PRP showed higher levels of TGF-β1 and VEGF at 10 days. While both formulations exhibited high biocompatibility and higher fibroblast migration and proliferation when compared to control tissue-culture plastic, i-PRF induced significantly highest migration whereas PRP demonstrated significantly highest cellular proliferation. Furthermore, i-PRF showed significantly highest mRNA levels of TGF-β at 7 days, PDGF at 3 days, and collagen1 expression at both 3 and 7 days when compared to PRP.

Conclusions

i-PRF demonstrated the ability to release higher concentrations of various growth factors and induced higher fibroblast migration and expression of PDGF, TGF-β, and collagen1. Future animal research is now necessary to further validate the use of i-PRF as a bioactive agent capable of stimulating tissue regeneration.

Clinical relevance

The findings from the present study demonstrate that a potent formulation of liquid platelet concentrates could be obtained without use of anti-coagulants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Chow TW, McIntire LV, Peterson DM (1983) Importance of plasma fibronectin in determining PFP and PRP clot mechanical properties. Thromb Res 29:243–248

    Article  PubMed  Google Scholar 

  2. Delaini F, Poggi A, Donati MB (1982) Enhanced affinity for arachidonic acid in platelet-rich plasma from rats with adriamycin-induced nephrotic syndrome. Thromb Haemost 48:260–262

    PubMed  Google Scholar 

  3. Marx RE (2004) Platelet-rich plasma: evidence to support its use. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 62:489–496

    Article  Google Scholar 

  4. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR (1998) Platelet-rich plasma: growth factor enhancement for bone grafts. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 85:638–646

    Article  PubMed  Google Scholar 

  5. Cai YZ, Zhang C, Lin XJ (2015) Efficacy of platelet-rich plasma in arthroscopic repair of full-thickness rotator cuff tears: a meta-analysis. Journal of shoulder and elbow surgery / American Shoulder and Elbow Surgeons [et al.] 24:1852–1859. doi:10.1016/j.jse.2015.07.035

    Article  Google Scholar 

  6. Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD (2016) Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association 32:495–505. doi:10.1016/j.arthro.2015.08.005

    Article  Google Scholar 

  7. Singh B, Goldberg LJ (2016) Autologous platelet-rich plasma for the treatment of pattern hair loss. Am J Clin Dermatol. doi:10.1007/s40257-016-0196-2

    Google Scholar 

  8. Anfossi G, Trovati M, Mularoni E, Massucco P, Calcamuggi G, Emanuelli G (1989) Influence of propranolol on platelet aggregation and thromboxane B2 production from platelet-rich plasma and whole blood. Prostaglandins Leukot Essent Fat Acids 36:1–7

    Article  Google Scholar 

  9. Fijnheer R, Pietersz RN, de Korte D, Gouwerok CW, Dekker WJ, Reesink HW, Roos D (1990) Platelet activation during preparation of platelet concentrates: a comparison of the platelet-rich plasma and the buffy coat methods. Transfusion 30:634–638

    Article  PubMed  Google Scholar 

  10. Choukroun J, Adda F, Schoeffler C, Vervelle A (2001) Une opportunité en paro-implantologie: le PRF. Implantodontie 42:e62

    Google Scholar 

  11. Toffler M (2014) Guided bone regeneration (GBR) using cortical bone pins in combination with leukocyte-and platelet-rich fibrin (L-PRF). Compendium of continuing education in dentistry (Jamesburg, NJ : 1995) 35:192–198

    Google Scholar 

  12. Lekovic V, Milinkovic I, Aleksic Z, Jankovic S, Stankovic P, Kenney E, Camargo P (2012) Platelet-rich fibrin and bovine porous bone mineral vs. platelet-rich fibrin in the treatment of intrabony periodontal defects. J Periodontal Res 47:409–417

    Article  PubMed  Google Scholar 

  13. Shivashankar VY, Johns DA, Vidyanath S, Sam G (2013) Combination of platelet rich fibrin, hydroxyapatite and PRF membrane in the management of large inflammatory periapical lesion. J Conserv Dent 16:261

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sammartino G, Dohan Ehrenfest DM, Carile F, Tia M, Bucci P (2011) Prevention of hemorrhagic complications after dental extractions into open heart surgery patients under anticoagulant therapy: the use of leukocyte- and platelet-rich fibrin. The Journal of oral implantology 37:681–690. doi:10.1563/aaid-joi-d-11-00001

    Article  PubMed  Google Scholar 

  15. Hoaglin DR, Lines GK (2013) Prevention of localized osteitis in mandibular third-molar sites using platelet-rich fibrin. International journal of dentistry 2013:875380. doi:10.1155/2013/875380

    Article  PubMed  PubMed Central  Google Scholar 

  16. Suttapreyasri S, Leepong N (2013) Influence of platelet-rich fibrin on alveolar ridge preservation. The Journal of craniofacial surgery 24:1088–1094. doi:10.1097/SCS.0b013e31828b6dc3

    Article  PubMed  Google Scholar 

  17. Yelamali T, Saikrishna D (2015) Role of platelet rich fibrin and platelet rich plasma in wound healing of extracted third molar sockets: a comparative study. Journal of maxillofacial and oral surgery 14:410–416. doi:10.1007/s12663-014-0638-4

    Article  PubMed  Google Scholar 

  18. Anilkumar K, Geetha A, Umasudhakar RT, Vijayalakshmi R, Pameela E (2009) Platelet-rich-fibrin: a novel root coverage approach. Journal of Indian Society of Periodontology 13:50–54. doi:10.4103/0972-124x.51897

    Article  PubMed  PubMed Central  Google Scholar 

  19. Jankovic S, Aleksic Z, Klokkevold P, Lekovic V, Dimitrijevic B, Kenney EB, Camargo P (2012) Use of platelet-rich fibrin membrane following treatment of gingival recession: a randomized clinical trial. The International journal of periodontics & restorative dentistry 32:e41–e50

    Google Scholar 

  20. Eren G, Tervahartiala T, Sorsa T, Atilla G (2015) Cytokine (interleukin-1beta) and MMP levels in gingival crevicular fluid after use of platelet-rich fibrin or connective tissue graft in the treatment of localized gingival recessions. J Periodontal Res. doi:10.1111/jre.12325

    PubMed  Google Scholar 

  21. Jain V, Triveni MG, Kumar AB, Mehta DS (2012) Role of platelet-rich-fibrin in enhancing palatal wound healing after free graft. Contemporary clinical dentistry 3:S240–S243. doi:10.4103/0976-237x.101105

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kulkarni MR, Thomas BS, Varghese JM, Bhat GS (2014) Platelet-rich fibrin as an adjunct to palatal wound healing after harvesting a free gingival graft: a case series. Journal of Indian Society of Periodontology 18:399–402. doi:10.4103/0972-124x.134591

    Article  PubMed  PubMed Central  Google Scholar 

  23. Femminella B, Iaconi MC, Di Tullio M, Romano L, Sinjari B, D'Arcangelo C, De Ninis P, Paolantonio M (2016) Clinical comparison of platelet-rich fibrin and a gelatin sponge in the management of palatal wounds after epithelialized free gingival graft harvest: a randomized clinical trial. J Periodontol 87:103–113. doi:10.1902/jop.2015.150198

    Article  PubMed  Google Scholar 

  24. Ajwani H, Shetty S, Gopalakrishnan D, Kathariya R, Kulloli A, Dolas RS, Pradeep AR (2015) Comparative evaluation of platelet-rich fibrin biomaterial and open flap debridement in the treatment of two and three wall intrabony defects. Journal of international oral health : JIOH 7:32–37

    PubMed  PubMed Central  Google Scholar 

  25. di Lauro AE, Abbate D, Dell'Angelo B, Iannaccone GA, Scotto F, Sammartino G (2015) Soft tissue regeneration using leukocyte-platelet rich fibrin after exeresis of hyperplastic gingival lesions: two case reports. J Med Case Rep 9:252. doi:10.1186/s13256-015-0714-5

    Article  PubMed  PubMed Central  Google Scholar 

  26. Miron RJ, Fujioka-Kobayashi M, Bishara M, Zhang Y, Hernandez M, Choukroun J (2016) Platelet-rich fibrin and soft tissue wound healing: a systematic review. Tissue Eng B Rev. doi:10.1089/ten.TEB.2016.0233

    Google Scholar 

  27. Medina-Porqueres I, Alvarez-Juarez P (2015) The efficacy of platelet-rich plasma injection in the management of hip osteoarthritis: a systematic review protocol. Musculoskeletal care. doi:10.1002/msc.1115

    PubMed  Google Scholar 

  28. Salamanna F, Veronesi F, Maglio M, Della Bella E (2015) New and emerging strategies in platelet-rich plasma application in musculoskeletal regenerative procedures. general overview on still open questions and outlook 2015:846045. doi:10.1155/2015/846045

    Google Scholar 

  29. Albanese A, Licata ME, Polizzi B, Campisi G (2013) Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration. Immunity & ageing : I & A 10:23. doi:10.1186/1742-4933-10-23

    Article  Google Scholar 

  30. Panda S, Doraiswamy J, Malaiappan S, Varghese SS, Del Fabbro M (2014) Additive effect of autologous platelet concentrates in treatment of intrabony defects: a systematic review and meta-analysis. J Investig Clin Dent. doi:10.1111/jicd.12117

    PubMed  Google Scholar 

  31. Peerbooms JC, van Laar W, Faber F, Schuller HM, van der Hoeven H, Gosens T (2010) Use of platelet rich plasma to treat plantar fasciitis: design of a multi centre randomized controlled trial. BMC Musculoskelet Disord 11:69–69. doi:10.1186/1471-2474-11-69

    Article  PubMed  PubMed Central  Google Scholar 

  32. Anitua E, Prado R, Troya M, Zalduendo M, de la Fuente M, Pino A, Muruzabal F, Orive G (2016) Implementation of a more physiological plasma rich in growth factor (PRGF) protocol: anticoagulant removal and reduction in activator concentration. Platelets 27:459–466. doi:10.3109/09537104.2016.1143921

    Article  PubMed  Google Scholar 

  33. Ghanaati S, Booms P, Orlowska A, Kubesch A, Lorenz J, Rutkowski J, Landes C, Sader R, Kirkpatrick C, Choukroun J (2014) Advanced platelet-rich fibrin: a new concept for cell-based tissue engineering by means of inflammatory cells. The Journal of oral implantology 40:679–689. doi:10.1563/aaid-joi-D-14-00138

    Article  PubMed  Google Scholar 

  34. Fujioka-Kobayashi M, Miron RJ, Hernandez M, Kandalam U, Zhang Y, Choukroun J (2016) Optimized platelet rich fibrin with the low speed concept: growth factor release, biocompatibility and cellular response. J Periodontol:1–17. doi:10.1902/jop.2016.160443

  35. Kobayashi E, Fluckiger L, Fujioka-Kobayashi M, Sawada K, Sculean A, Schaller B, Miron RJ (2016) Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clinical oral investigations. doi:10.1007/s00784-016-1719-1

    Google Scholar 

  36. Miron RJ, Bosshardt DD, Hedbom E, Zhang Y, Haenni B, Buser D, Sculean A (2012) Adsorption of enamel matrix proteins to a bovine-derived bone grafting material and its regulation of cell adhesion, proliferation, and differentiation. J Periodontol 83:936–947. doi:10.1902/jop.2011.110480

    Article  PubMed  Google Scholar 

  37. Horowitz R, Holtzclaw D, Rosen PS (2012) A review on alveolar ridge preservation following tooth extraction. The journal of evidence-based dental practice 12:149–160. doi:10.1016/s1532-3382(12)70029-5

    Article  PubMed  Google Scholar 

  38. Lee CT, Chiu TS, Chuang SK, Tarnow D, Stoupel J (2014) Alterations of the bone dimension following immediate implant placement into extraction socket: systematic review and meta-analysis. J Clin Periodontol 41:914–926. doi:10.1111/jcpe.12276

    Article  PubMed  Google Scholar 

  39. Morjaria KR, Wilson R, Palmer RM (2014) Bone healing after tooth extraction with or without an intervention: a systematic review of randomized controlled trials. Clin Implant Dent Relat Res 16:1–20. doi:10.1111/j.1708-8208.2012.00450.x

    Article  PubMed  Google Scholar 

  40. Tan WL, Wong TL, Wong MC, Lang NP (2012) A systematic review of post-extractional alveolar hard and soft tissue dimensional changes in humans. Clin Oral Implants Res 23(Suppl 5):1–21. doi:10.1111/j.1600-0501.2011.02375.x

    Article  PubMed  Google Scholar 

  41. Bielecki T, Dohan Ehrenfest DM, Everts PA, Wiczkowski A (2012) The role of leukocytes from L-PRP/L-PRF in wound healing and immune defense: new perspectives. Curr Pharm Biotechnol 13:1153–1162

    Article  PubMed  Google Scholar 

  42. Martin P (1997) Wound healing--aiming for perfect skin regeneration. Science 276:75–81

    Article  PubMed  Google Scholar 

  43. Barrick B, Campbell EJ, Owen CA (1999) Leukocyte proteinases in wound healing: roles in physiologic and pathologic processes. Wound Repair Regen 7:410–422

    Article  PubMed  Google Scholar 

  44. Anitua E (1999) Plasma rich in growth factors: preliminary results of use in the preparation of future sites for implants. Int J Oral Maxillofac Implants 14:529–535

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Periodontology, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA

    Richard J. Miron, Masako Fujioka-Kobayashi & Maria Hernandez

  2. Cell Therapy Institute, Center for Collaborative Research, Nova Southeastern University, Fort Lauderdale, FL, USA

    Richard J. Miron

  3. Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI, USA

    Richard J. Miron

  4. Department of Cranio-Maxillofacial Surgery, University of Bern, Bern, Switzerland

    Masako Fujioka-Kobayashi

  5. Department of Oral Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan

    Masako Fujioka-Kobayashi

  6. Department of Pediatric Dentistry, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA

    Umadevi Kandalam

  7. Department of Oral Implantology, University of Wuhan, Wuhan, China

    Yufeng Zhang

  8. FORM, Frankfurt Oral Regenerative Medicine, Clinic for Maxillofacial and Plastic Surgery, Johann Wolfgang Goethe University, Frankfurt Am Main, Germany

    Shahram Ghanaati

  9. Pain Clinic, Nice, France

    Joseph Choukroun

Authors
  1. Richard J. Miron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masako Fujioka-Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Hernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Umadevi Kandalam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yufeng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shahram Ghanaati
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joseph Choukroun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard J. Miron.

Ethics declarations

Conflict of interest

Joseph Choukroun is the founder of Process of PRF company and the developer and inventor of the PRF protocol in Nice, France. All other authors declare no conflict of interests.

Funding

This work was fully funded by the Cell Biology Laboratory at Nova Southeastern University, College of Dental Medicine.

Ethical approval

No ethical approval was required for this study as human samples were not identified in this study.

Informed consent

For this type of study, informed consent was not required as no human or animal subjects were utilized.

Additional information

Richard J. Miron and Masako Fujioka-Kobayashi contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miron, R.J., Fujioka-Kobayashi, M., Hernandez, M. et al. Injectable platelet rich fibrin (i-PRF): opportunities in regenerative dentistry?. Clin Oral Invest 21, 2619–2627 (2017). https://doi.org/10.1007/s00784-017-2063-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-017-2063-9

Keywords

Search

Navigation