Skip to main content
Top
Published in: Clinical Oral Investigations 9/2016

01-12-2016 | Original Article

Comparative release of growth factors from PRP, PRF, and advanced-PRF

Authors: Eizaburo Kobayashi, Laura Flückiger, Masako Fujioka-Kobayashi, Kosaku Sawada, Anton Sculean, Benoit Schaller, Richard J. Miron

Published in: Clinical Oral Investigations | Issue 9/2016

Login to get access

Abstract

Objectives

The use of platelet concentrates has gained increasing awareness in recent years for regenerative procedures in modern dentistry. The aim of the present study was to compare growth factor release over time from platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and a modernized protocol for PRF, advanced-PRF (A-PRF).

Materials and methods

Eighteen blood samples were collected from six donors (3 samples each for PRP, PRF, and A-PRF). Following preparation, samples were incubated in a plate shaker and assessed for growth factor release at 15 min, 60 min, 8 h, 1 day, 3 days, and 10 days. Thereafter, growth factor release of PDGF-AA, PDGF-AB, PDGF-BB, TGFB1, VEGF, EGF, and IGF was quantified using ELISA.

Results

The highest reported growth factor released from platelet concentrates was PDGF-AA followed by PDGF-BB, TGFB1, VEGF, and PDGF-AB. In general, following 15–60 min incubation, PRP released significantly higher growth factors when compared to PRF and A-PRF. At later time points up to 10 days, it was routinely found that A-PRF released the highest total growth factors. Furthermore, A-PRF released significantly higher total protein accumulated over a 10-day period when compared to PRP or PRF.

Conclusion

The results from the present study indicate that the various platelet concentrates have quite different release kinetics. The advantage of PRP is the release of significantly higher proteins at earlier time points whereas PRF displayed a continual and steady release of growth factors over a 10-day period. Furthermore, in general, it was observed that the new formulation of PRF (A-PRF) released significantly higher total quantities of growth factors when compared to traditional PRF.

Clinical relevance

Based on these findings, PRP can be recommended for fast delivery of growth factors whereas A-PRF is better-suited for long-term release.
Literature
2.
go back to reference Padial-Molina M, O’Valle F, Lanis A and Mesa F (2015) Clinical application of mesenchymal stem cells and novel supportive therapies for oral bone regeneration. Biomed Res Int 2015:341327. doi:10.1155/2015/341327 Padial-Molina M, O’Valle F, Lanis A and Mesa F (2015) Clinical application of mesenchymal stem cells and novel supportive therapies for oral bone regeneration. Biomed Res Int 2015:341327. doi:10.​1155/​2015/​341327
3.
go back to reference Sanz-Sanchez I, Ortiz-Vigon A, Sanz-Martin I, Figuero E, Sanz M (2015) Effectiveness of lateral bone augmentation on the alveolar crest dimension: a systematic review and meta-analysis. J Dent Res 94:128s–142s. doi:10.1177/0022034515594780 CrossRefPubMed Sanz-Sanchez I, Ortiz-Vigon A, Sanz-Martin I, Figuero E, Sanz M (2015) Effectiveness of lateral bone augmentation on the alveolar crest dimension: a systematic review and meta-analysis. J Dent Res 94:128s–142s. doi:10.​1177/​0022034515594780​ CrossRefPubMed
5.
go back to reference Anusaksathien O, Giannobile WV (2002) Growth factor delivery to re-engineer periodontal tissues. Curr Pharm Biotechnol 3:129–139CrossRefPubMed Anusaksathien O, Giannobile WV (2002) Growth factor delivery to re-engineer periodontal tissues. Curr Pharm Biotechnol 3:129–139CrossRefPubMed
7.
go back to reference Rocque BG, Kelly MP, Miller JH, Li Y, Anderson PA (2014) Bone morphogenetic protein-associated complications in pediatric spinal fusion in the early postoperative period: an analysis of 4658 patients and review of the literature. J Neurosurg Pediatr 14:635–643. doi:10.3171/2014.8.peds13665 CrossRefPubMed Rocque BG, Kelly MP, Miller JH, Li Y, Anderson PA (2014) Bone morphogenetic protein-associated complications in pediatric spinal fusion in the early postoperative period: an analysis of 4658 patients and review of the literature. J Neurosurg Pediatr 14:635–643. doi:10.​3171/​2014.​8.​peds13665 CrossRefPubMed
9.
go back to reference Del Corso M, Vervelle A, Simonpieri A, Jimbo R, Inchingolo F, Sammartino G, Dohan Ehrenfest DM (2012) Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 1: periodontal and dentoalveolar surgery. Curr Pharm Biotechnol 13:1207–1230CrossRefPubMed Del Corso M, Vervelle A, Simonpieri A, Jimbo R, Inchingolo F, Sammartino G, Dohan Ehrenfest DM (2012) Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 1: periodontal and dentoalveolar surgery. Curr Pharm Biotechnol 13:1207–1230CrossRefPubMed
10.
go back to reference Simonpieri A, Del Corso M, Vervelle A, Jimbo R, Inchingolo F, Sammartino G, Dohan Ehrenfest DM (2012) Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 2: bone graft, implant and reconstructive surgery. Curr Pharm Biotechnol 13:1231–1256CrossRefPubMed Simonpieri A, Del Corso M, Vervelle A, Jimbo R, Inchingolo F, Sammartino G, Dohan Ehrenfest DM (2012) Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 2: bone graft, implant and reconstructive surgery. Curr Pharm Biotechnol 13:1231–1256CrossRefPubMed
11.
go back to reference 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
12.
go back to reference Salamanna F, Veronesi F, Maglio M and 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 and 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
14.
go back to reference Dohan Ehrenfest DM, Andia I, Zumstein MA, Zhang CQ, Pinto NR, Bielecki T (2014) Classification of platelet concentrates (platelet-rich plasma-PRP, platelet-rich fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles, Ligament Tendons J 4:3–9 Dohan Ehrenfest DM, Andia I, Zumstein MA, Zhang CQ, Pinto NR, Bielecki T (2014) Classification of platelet concentrates (platelet-rich plasma-PRP, platelet-rich fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles, Ligament Tendons J 4:3–9
15.
go back to reference Maney P, Amornporncharoen M, Palaiologou A (2013) Applications of plasma rich in growth factors (PRGF) in dental surgery: a review. J West Soc of Periodontol Periodontal Abstr 61:99–104 Maney P, Amornporncharoen M, Palaiologou A (2013) Applications of plasma rich in growth factors (PRGF) in dental surgery: a review. J West Soc of Periodontol Periodontal Abstr 61:99–104
16.
go back to reference Panda S, Doraiswamy J, Malaiappan S, Varghese SS and 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 Panda S, Doraiswamy J, Malaiappan S, Varghese SS and 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
17.
go back to reference Marx RE (2001) Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent 10:225–228CrossRefPubMed Marx RE (2001) Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent 10:225–228CrossRefPubMed
18.
go back to reference Marx RE (2004) Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg 62:489–496CrossRef Marx RE (2004) Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg 62:489–496CrossRef
19.
go back to reference Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR (1998) Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 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 Surg Oral Med Oral Pathol Oral Radiol Endod 85:638–646CrossRefPubMed
20.
go back to reference Kukreja BJ, Dodwad V, Kukreja P, Ahuja S, Mehra P (2014) A comparative evaluation of platelet-rich plasma in combination with demineralized freeze-dried bone allograft and DFDBA alone in the treatment of periodontal intrabony defects: a clinicoradiographic study. J Indian Soc of Periodontol 18:618–623. doi:10.4103/0972-124x.142457 CrossRef Kukreja BJ, Dodwad V, Kukreja P, Ahuja S, Mehra P (2014) A comparative evaluation of platelet-rich plasma in combination with demineralized freeze-dried bone allograft and DFDBA alone in the treatment of periodontal intrabony defects: a clinicoradiographic study. J Indian Soc of Periodontol 18:618–623. doi:10.​4103/​0972-124x.​142457 CrossRef
21.
go back to reference Pradeep AR, Rao NS, Agarwal E, Bajaj P, Kumari M, Naik SB (2012) Comparative evaluation of autologous platelet-rich fibrin and platelet-rich plasma in the treatment of 3-wall intrabony defects in chronic periodontitis: a randomized controlled clinical trial. J Periodontol 83:1499–1507. doi:10.1902/jop.2012.110705 CrossRefPubMed Pradeep AR, Rao NS, Agarwal E, Bajaj P, Kumari M, Naik SB (2012) Comparative evaluation of autologous platelet-rich fibrin and platelet-rich plasma in the treatment of 3-wall intrabony defects in chronic periodontitis: a randomized controlled clinical trial. J Periodontol 83:1499–1507. doi:10.​1902/​jop.​2012.​110705 CrossRefPubMed
22.
go back to reference Dori F, Arweiler N, Huszar T, Gera I, Miron RJ, Sculean A (2013) Five-year results evaluating the effects of platelet-rich plasma on the healing of intrabony defects treated with enamel matrix derivative and natural bone mineral. J Periodontol 84:1546–1555. doi:10.1902/jop.2013.120501 CrossRefPubMed Dori F, Arweiler N, Huszar T, Gera I, Miron RJ, Sculean A (2013) Five-year results evaluating the effects of platelet-rich plasma on the healing of intrabony defects treated with enamel matrix derivative and natural bone mineral. J Periodontol 84:1546–1555. doi:10.​1902/​jop.​2013.​120501 CrossRefPubMed
23.
go back to reference Ozdemir B, Okte E (2012) Treatment of intrabony defects with beta-tricalciumphosphate alone and in combination with platelet-rich plasma. J Biomed Mater Res B, Appl Biomater 100:976–983. doi:10.1002/jbm.b.32660 CrossRef Ozdemir B, Okte E (2012) Treatment of intrabony defects with beta-tricalciumphosphate alone and in combination with platelet-rich plasma. J Biomed Mater Res B, Appl Biomater 100:976–983. doi:10.​1002/​jbm.​b.​32660 CrossRef
24.
go back to reference Yilmaz S, Kabadayi C, Ipci SD, Cakar G, Kuru B (2011) Treatment of intrabony periodontal defects with platelet-rich plasma versus platelet-poor plasma combined with a bovine-derived xenograft: a controlled clinical trial. J Periodontol 82:837–844. doi:10.1902/jop.2010.100503 CrossRefPubMed Yilmaz S, Kabadayi C, Ipci SD, Cakar G, Kuru B (2011) Treatment of intrabony periodontal defects with platelet-rich plasma versus platelet-poor plasma combined with a bovine-derived xenograft: a controlled clinical trial. J Periodontol 82:837–844. doi:10.​1902/​jop.​2010.​100503 CrossRefPubMed
25.
go back to reference Camargo PM, Lekovic V, Weinlaender M, Divnic-Resnik T, Pavlovic M, Kenney EB (2009) A surgical reentry study on the influence of platelet-rich plasma in enhancing the regenerative effects of bovine porous bone mineral and guided tissue regeneration in the treatment of intrabony defects in humans. J Periodontol 80:915–923. doi:10.1902/jop.2009.080600 CrossRefPubMed Camargo PM, Lekovic V, Weinlaender M, Divnic-Resnik T, Pavlovic M, Kenney EB (2009) A surgical reentry study on the influence of platelet-rich plasma in enhancing the regenerative effects of bovine porous bone mineral and guided tissue regeneration in the treatment of intrabony defects in humans. J Periodontol 80:915–923. doi:10.​1902/​jop.​2009.​080600 CrossRefPubMed
26.
go back to reference Camargo PM, Lekovic V, Weinlaender M, Vasilic N, Madzarevic M, Kenney EB (2005) A reentry study on the use of bovine porous bone mineral, GTR, and platelet-rich plasma in the regenerative treatment of intrabony defects in humans. Int J Periodontics Restorative Dent 25:49–59PubMed Camargo PM, Lekovic V, Weinlaender M, Vasilic N, Madzarevic M, Kenney EB (2005) A reentry study on the use of bovine porous bone mineral, GTR, and platelet-rich plasma in the regenerative treatment of intrabony defects in humans. Int J Periodontics Restorative Dent 25:49–59PubMed
27.
go back to reference Yassibag-Berkman Z, Tuncer O, Subasioglu T, Kantarci A (2007) Combined use of platelet-rich plasma and bone grafting with or without guided tissue regeneration in the treatment of anterior interproximal defects. J Periodontol 78:801–809. doi:10.1902/jop.2007.060318 CrossRefPubMed Yassibag-Berkman Z, Tuncer O, Subasioglu T, Kantarci A (2007) Combined use of platelet-rich plasma and bone grafting with or without guided tissue regeneration in the treatment of anterior interproximal defects. J Periodontol 78:801–809. doi:10.​1902/​jop.​2007.​060318 CrossRefPubMed
28.
go back to reference Choukroun J, Diss A, Simonpieri A, Girard MO, Schoeffler C, Dohan SL, Dohan AJ, Mouhyi J, Dohan DM (2006) 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 101:299–303. doi:10.1016/j.tripleo.2005.07.012 CrossRefPubMed Choukroun J, Diss A, Simonpieri A, Girard MO, Schoeffler C, Dohan SL, Dohan AJ, Mouhyi J, Dohan DM (2006) 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 101:299–303. doi:10.​1016/​j.​tripleo.​2005.​07.​012 CrossRefPubMed
29.
go back to reference Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, Gogly B (2006) Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:e45–e50. doi:10.1016/j.tripleo.2005.07.009 CrossRefPubMed Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, Gogly B (2006) Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:e45–e50. doi:10.​1016/​j.​tripleo.​2005.​07.​009 CrossRefPubMed
30.
go back to reference Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, Gogly B (2006) Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:e37–e44. doi:10.1016/j.tripleo.2005.07.008 CrossRefPubMed Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, Gogly B (2006) Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:e37–e44. doi:10.​1016/​j.​tripleo.​2005.​07.​008 CrossRefPubMed
31.
go back to reference Sunitha Raja V, Munirathnam Naidu E (2008) Platelet-rich fibrin: evolution of a second-generation platelet concentrate. Indian J Dent Res Off Publ Indian Soc Dental Res 19:42–46CrossRef Sunitha Raja V, Munirathnam Naidu E (2008) Platelet-rich fibrin: evolution of a second-generation platelet concentrate. Indian J Dent Res Off Publ Indian Soc Dental Res 19:42–46CrossRef
32.
go back to reference Man D, Plosker H, Winland-Brown JE (2001) The use of autologous platelet-rich plasma (platelet gel) and autologous platelet-poor plasma (fibrin glue) in cosmetic surgery. Plast Reconstr Surg 107:229–237 discussion 238-9CrossRefPubMed Man D, Plosker H, Winland-Brown JE (2001) The use of autologous platelet-rich plasma (platelet gel) and autologous platelet-poor plasma (fibrin glue) in cosmetic surgery. Plast Reconstr Surg 107:229–237 discussion 238-9CrossRefPubMed
33.
35.
go back to reference Sharma A, Pradeep AR (2011) Treatment of 3-wall intrabony defects in patients with chronic periodontitis with autologous platelet-rich fibrin: a randomized controlled clinical trial. J Periodontol 82:1705–1712. doi:10.1902/jop.2011.110075 CrossRefPubMed Sharma A, Pradeep AR (2011) Treatment of 3-wall intrabony defects in patients with chronic periodontitis with autologous platelet-rich fibrin: a randomized controlled clinical trial. J Periodontol 82:1705–1712. doi:10.​1902/​jop.​2011.​110075 CrossRefPubMed
37.
go back to reference 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. J Oral Implantol 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. J Oral Implantol 40:679–689. doi:10.​1563/​aaid-joi-D-14-00138 CrossRefPubMed
41.
42.
go back to reference Okuda K, Kawase T, Momose M, Murata M, Saito Y, Suzuki H, Wolff LF, Yoshie H (2003) Platelet-rich plasma contains high levels of platelet-derived growth factor and transforming growth factor-beta and modulates the proliferation of periodontally related cells in vitro. J Periodontol 74:849–857. doi:10.1902/jop.2003.74.6.849 CrossRefPubMed Okuda K, Kawase T, Momose M, Murata M, Saito Y, Suzuki H, Wolff LF, Yoshie H (2003) Platelet-rich plasma contains high levels of platelet-derived growth factor and transforming growth factor-beta and modulates the proliferation of periodontally related cells in vitro. J Periodontol 74:849–857. doi:10.​1902/​jop.​2003.​74.​6.​849 CrossRefPubMed
44.
go back to reference Fan WJ, Yang M, Zhang C, Xue R, Zhang W, Qin HX (2013) Effects of Choukroun’s platelet-rich fibrin on human gingival fibroblasts proliferation, migration and type I collagen secretion. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi =. Chin J Stomatol 48:72–76 Fan WJ, Yang M, Zhang C, Xue R, Zhang W, Qin HX (2013) Effects of Choukroun’s platelet-rich fibrin on human gingival fibroblasts proliferation, migration and type I collagen secretion. Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi =. Chin J Stomatol 48:72–76
45.
go back to reference Dohan Ehrenfest DM, Doglioli P, de Peppo GM, Del Corso M, Charrier JB (2010) Choukroun’s platelet-rich fibrin (PRF) stimulates in vitro proliferation and differentiation of human oral bone mesenchymal stem cell in a dose-dependent way. Arch Oral Biol 55:185–194. doi:10.1016/j.archoralbio.2010.01.004 CrossRefPubMed Dohan Ehrenfest DM, Doglioli P, de Peppo GM, Del Corso M, Charrier JB (2010) Choukroun’s platelet-rich fibrin (PRF) stimulates in vitro proliferation and differentiation of human oral bone mesenchymal stem cell in a dose-dependent way. Arch Oral Biol 55:185–194. doi:10.​1016/​j.​archoralbio.​2010.​01.​004 CrossRefPubMed
46.
go back to reference Kawase T, Okuda K, Saito Y, Amizuka N, Suzuki H, Yoshie H (2005) Platelet-rich plasma provides nucleus for mineralization in cultures of partially differentiated periodontal ligament cells. In Vitro Cell Dev Biol Anim 41:171–176. doi:10.1290/0502013.1 CrossRefPubMed Kawase T, Okuda K, Saito Y, Amizuka N, Suzuki H, Yoshie H (2005) Platelet-rich plasma provides nucleus for mineralization in cultures of partially differentiated periodontal ligament cells. In Vitro Cell Dev Biol Anim 41:171–176. doi:10.​1290/​0502013.​1 CrossRefPubMed
47.
go back to reference Kawase T, Tanaka T, Okuda K, Tsuchimochi M, Oda M, Hara T (2015) Quantitative single-cell motility analysis of platelet-rich plasma-treated endothelial cells in vitro. Cytoskeleton (Hoboken, NJ) 72:246–255. doi:10.1002/cm.21221 CrossRef Kawase T, Tanaka T, Okuda K, Tsuchimochi M, Oda M, Hara T (2015) Quantitative single-cell motility analysis of platelet-rich plasma-treated endothelial cells in vitro. Cytoskeleton (Hoboken, NJ) 72:246–255. doi:10.​1002/​cm.​21221 CrossRef
Metadata
Title
Comparative release of growth factors from PRP, PRF, and advanced-PRF
Authors
Eizaburo Kobayashi
Laura Flückiger
Masako Fujioka-Kobayashi
Kosaku Sawada
Anton Sculean
Benoit Schaller
Richard J. Miron
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 9/2016
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-016-1719-1

Other articles of this Issue 9/2016

Clinical Oral Investigations 9/2016 Go to the issue