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Erschienen in: Clinical Oral Investigations 8/2017

02.02.2017 | Original Article

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

verfasst von: Richard J. Miron, Masako Fujioka-Kobayashi, Maria Hernandez, Umadevi Kandalam, Yufeng Zhang, Shahram Ghanaati, Joseph Choukroun

Erschienen in: Clinical Oral Investigations | Ausgabe 8/2017

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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.
Literatur
1.
Zurück zum Zitat Chow TW, McIntire LV, Peterson DM (1983) Importance of plasma fibronectin in determining PFP and PRP clot mechanical properties. Thromb Res 29:243–248CrossRefPubMed Chow TW, McIntire LV, Peterson DM (1983) Importance of plasma fibronectin in determining PFP and PRP clot mechanical properties. Thromb Res 29:243–248CrossRefPubMed
2.
Zurück zum Zitat 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 48:260–262PubMed 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 48:260–262PubMed
3.
Zurück zum Zitat 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 62:489–496CrossRef 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 62:489–496CrossRef
4.
Zurück zum Zitat 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 85:638–646CrossRefPubMed 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 85:638–646CrossRefPubMed
5.
Zurück zum Zitat 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 CrossRef 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 CrossRef
6.
Zurück zum Zitat 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 CrossRef 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 CrossRef
8.
Zurück zum Zitat 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 36:1–7CrossRef 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 36:1–7CrossRef
9.
Zurück zum Zitat 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 30:634–638CrossRefPubMed 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 30:634–638CrossRefPubMed
10.
Zurück zum Zitat Choukroun J, Adda F, Schoeffler C, Vervelle A (2001) Une opportunité en paro-implantologie: le PRF. Implantodontie 42:e62 Choukroun J, Adda F, Schoeffler C, Vervelle A (2001) Une opportunité en paro-implantologie: le PRF. Implantodontie 42:e62
11.
Zurück zum Zitat 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 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
12.
Zurück zum Zitat 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 47:409–417CrossRefPubMed 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 47:409–417CrossRefPubMed
13.
Zurück zum Zitat 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 16:261CrossRefPubMedPubMedCentral 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 16:261CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
17.
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
19.
Zurück zum Zitat 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 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
20.
Zurück zum Zitat 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 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
23.
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
24.
Zurück zum Zitat 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 7:32–37PubMedPubMedCentral 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 7:32–37PubMedPubMedCentral
26.
Zurück zum Zitat 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 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
27.
Zurück zum Zitat 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 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
28.
Zurück zum Zitat 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 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
29.
Zurück zum Zitat 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 CrossRef 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 CrossRef
30.
Zurück zum Zitat 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 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
32.
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
33.
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
34.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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
36.
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
38.
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
41.
Zurück zum Zitat 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 13:1153–1162CrossRefPubMed 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 13:1153–1162CrossRefPubMed
42.
43.
Zurück zum Zitat Barrick B, Campbell EJ, Owen CA (1999) Leukocyte proteinases in wound healing: roles in physiologic and pathologic processes. Wound Repair Regen 7:410–422CrossRefPubMed Barrick B, Campbell EJ, Owen CA (1999) Leukocyte proteinases in wound healing: roles in physiologic and pathologic processes. Wound Repair Regen 7:410–422CrossRefPubMed
44.
Zurück zum Zitat 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 14:529–535PubMed 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 14:529–535PubMed
Metadaten
Titel
Injectable platelet rich fibrin (i-PRF): opportunities in regenerative dentistry?
verfasst von
Richard J. Miron
Masako Fujioka-Kobayashi
Maria Hernandez
Umadevi Kandalam
Yufeng Zhang
Shahram Ghanaati
Joseph Choukroun
Publikationsdatum
02.02.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Oral Investigations / Ausgabe 8/2017
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-017-2063-9

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