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Published in: International Orthopaedics 2/2017

Open Access 01-02-2017 | Review Article

Platelet-rich plasma for the treatment of bone defects: from pre-clinical rational to evidence in the clinical practice. A systematic review

Authors: Alice Roffi, Berardo Di Matteo, Gopal Shankar Krishnakumar, Elizaveta Kon, Giuseppe Filardo

Published in: International Orthopaedics | Issue 2/2017

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Abstract

Purpose

The treatment of large bone defects represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have also been used to further improve bone healing. Among these, platelet-rich plasma (PRP) is the most exploited strategy. The aim of the present study was to systematically review the available literature to identify: 1) preclinical in-vivo results supporting the rational of PRP use for bone healing; 2) evidence from the clinical practice on the actual clinical benefit of PRP for the treatment of fractures and complications such as delayed unions and non-unions.

Methods

A systematic review of the literature was performed on the application of PRP in bone healing, using the following inclusion criteria: pre-clinical and clinical reports of any level of evidence, written in English language, published in the last 20 years (1996–2016), on the use of PRP to stimulate long-bone defect treatment, with focus on fracture and delayed/non-unions healing.

Results

The search in the Pubmed database identified 64 articles eligible for inclusion: 45 were preclinical in-vivo studies and 19 were clinical studies. Despite the fact that the overall pre-clinical results seem to support the benefit of PRP in 91.1 % of the studies, a more in depth analysis underlined a lower success rate, with a positive outcome of 84.4 % in terms of histological analysis, and even lower values considering radiological and biomechanical results (75.0 % and 72.7 % positive outcome respectively). This was also mirrored in the clinical literature, where the real benefit of PRP use to treat fractures and non-unions is still under debate.

Conclusion

Overall, the available literature presents major limitations in terms of low quality and extreme heterogeneity, which hamper the possibility to optimize PRP treatment and translate it into a real clinical benefit despite positive preclinical findings on its biological potential to favour bone healing.
Literature
1.
go back to reference Nair MB, Varma HK, Menon KV, Shenoy SJ, John A (2009) Reconstruction of goat femur segmental defects using triphasic ceramic-coated hydroxyapatite in combination with autologous cells and platelet-rich plasma. Acta Biomater 5(5):1742–1755CrossRefPubMed Nair MB, Varma HK, Menon KV, Shenoy SJ, John A (2009) Reconstruction of goat femur segmental defects using triphasic ceramic-coated hydroxyapatite in combination with autologous cells and platelet-rich plasma. Acta Biomater 5(5):1742–1755CrossRefPubMed
2.
go back to reference He F, Chen Y, Li J, Lin B, Ouyang Y, Yu B, Xia Y, Yu B, Ye J (2015) Improving bone repair of femoral and radial defects in rabbit by incorporating PRP into PLGA/CPC composite scaffold with unidirectional pore structure. J Biomed Mater Res A 103(4):1312–1324CrossRefPubMed He F, Chen Y, Li J, Lin B, Ouyang Y, Yu B, Xia Y, Yu B, Ye J (2015) Improving bone repair of femoral and radial defects in rabbit by incorporating PRP into PLGA/CPC composite scaffold with unidirectional pore structure. J Biomed Mater Res A 103(4):1312–1324CrossRefPubMed
3.
go back to reference Stevens MM (2008) Biomaterials for bone tissue engineering. Mater Today 11(5):18–25CrossRef Stevens MM (2008) Biomaterials for bone tissue engineering. Mater Today 11(5):18–25CrossRef
4.
go back to reference Sarkar MR, Augat P, Shefelbine SJ, Schorlemmer S, Huber-Lang M, Claes L, Kinzl L, Ignatius A (2006) Bone formation in a long bone defect model using a platelet-rich plasma-loaded collagen scaffold. Biomaterials 27(9):1817–1823CrossRefPubMed Sarkar MR, Augat P, Shefelbine SJ, Schorlemmer S, Huber-Lang M, Claes L, Kinzl L, Ignatius A (2006) Bone formation in a long bone defect model using a platelet-rich plasma-loaded collagen scaffold. Biomaterials 27(9):1817–1823CrossRefPubMed
5.
go back to reference Roffi A, Filardo G, Kon E, Marcacci M (2013) Does PRP enhance bone integration with grafts, graft substitutes, or implants? A systematic review. BMC Musculoskelet Disord 14:330CrossRefPubMedPubMedCentral Roffi A, Filardo G, Kon E, Marcacci M (2013) Does PRP enhance bone integration with grafts, graft substitutes, or implants? A systematic review. BMC Musculoskelet Disord 14:330CrossRefPubMedPubMedCentral
6.
go back to reference Gazdag AR, Lane JM, Glaser D, Forster RA (1995) Alternatives to autogenous bone graft: efficacy and indications. J Am Acad Orthop Surg 3(1):1–8 Gazdag AR, Lane JM, Glaser D, Forster RA (1995) Alternatives to autogenous bone graft: efficacy and indications. J Am Acad Orthop Surg 3(1):1–8
7.
go back to reference Wang W, Ouyang Y, Poh CK (2011) Orthopaedic implant technology: biomaterials from past to future. Ann Acad Med Singapore 40(5):237–244PubMed Wang W, Ouyang Y, Poh CK (2011) Orthopaedic implant technology: biomaterials from past to future. Ann Acad Med Singapore 40(5):237–244PubMed
8.
go back to reference Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am 84-A(6):1032–1044CrossRefPubMed Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am 84-A(6):1032–1044CrossRefPubMed
9.
go back to reference Hakimi M, Grassmann JP, Betsch M, Schneppendahl J, Gehrmann S, Hakimi AR, Kröpil P, Sager M, Herten M, Wild M, Windolf J, Jungbluth P (2014) The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting. PLoS One 9(6), e100143CrossRefPubMedPubMedCentral Hakimi M, Grassmann JP, Betsch M, Schneppendahl J, Gehrmann S, Hakimi AR, Kröpil P, Sager M, Herten M, Wild M, Windolf J, Jungbluth P (2014) The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting. PLoS One 9(6), e100143CrossRefPubMedPubMedCentral
10.
go back to reference Brownlow HC, Simpson AH (2000) Metabolic activity of a new atrophic nonunion model in rabbits. J Orthop Res 18(3):438–442CrossRefPubMed Brownlow HC, Simpson AH (2000) Metabolic activity of a new atrophic nonunion model in rabbits. J Orthop Res 18(3):438–442CrossRefPubMed
11.
go back to reference Di Matteo B, Filardo G, Kon E, Marcacci M (2015) Platelet-rich plasma: evidence for the treatment of patellar and Achilles tendinopathy-a systematic review. Musculoskelet Surg 99(1):1–9CrossRefPubMed Di Matteo B, Filardo G, Kon E, Marcacci M (2015) Platelet-rich plasma: evidence for the treatment of patellar and Achilles tendinopathy-a systematic review. Musculoskelet Surg 99(1):1–9CrossRefPubMed
12.
go back to reference Rodriguez IA, Growney Kalaf EA, Bowlin GL, Sell SA (2014) Platelet-rich plasma in bone regeneration: engineering the delivery for improved clinical efficacy. Biomed Res Int. doi:10.1155/2014/392398 Rodriguez IA, Growney Kalaf EA, Bowlin GL, Sell SA (2014) Platelet-rich plasma in bone regeneration: engineering the delivery for improved clinical efficacy. Biomed Res Int. doi:10.​1155/​2014/​392398
13.
go back to reference Kasten P, Vogel J, Luginbühl R, Niemeyer P, Weiss S, Schneider S, Kramer M, Leo A, Richter W (2006) Influence of platelet-rich plasma on osteogenic differentiation of mesenchymal stem cells and ectopic bone formation in calcium phosphate ceramics. Cells Tissues Organs 183(2):68–79CrossRefPubMed Kasten P, Vogel J, Luginbühl R, Niemeyer P, Weiss S, Schneider S, Kramer M, Leo A, Richter W (2006) Influence of platelet-rich plasma on osteogenic differentiation of mesenchymal stem cells and ectopic bone formation in calcium phosphate ceramics. Cells Tissues Organs 183(2):68–79CrossRefPubMed
14.
go back to reference El Backly RM, Zaky SH, Muraglia A, Tonachini L, Brun F, Canciani B, Chiapale D, Santolini F, Cancedda R, Mastrogiacomo M (2013) A platelet-rich plasma-based membrane as a periosteal substitute with enhanced osteogenic and angiogenic properties: a new concept for bone repair. Tissue Eng Part A 19(1–2):152–165CrossRefPubMed El Backly RM, Zaky SH, Muraglia A, Tonachini L, Brun F, Canciani B, Chiapale D, Santolini F, Cancedda R, Mastrogiacomo M (2013) A platelet-rich plasma-based membrane as a periosteal substitute with enhanced osteogenic and angiogenic properties: a new concept for bone repair. Tissue Eng Part A 19(1–2):152–165CrossRefPubMed
15.
go back to reference McLaughlin M, Gagnet P, Cunningham E, Yeager R, D’Amico M, Guski K, Scarpone M, Kuebler D (2016) Allogeneic platelet releasate preparations derived via a novel rapid thrombin activationp process promote rapid growth and increased BMP-2 and BMP-4 expression in human adipose-derived stem cells. Stem Cells Int. doi:10.1155/2016/7183734 McLaughlin M, Gagnet P, Cunningham E, Yeager R, D’Amico M, Guski K, Scarpone M, Kuebler D (2016) Allogeneic platelet releasate preparations derived via a novel rapid thrombin activationp process promote rapid growth and increased BMP-2 and BMP-4 expression in human adipose-derived stem cells. Stem Cells Int. doi:10.​1155/​2016/​7183734
16.
go back to reference Casati L, Celotti F, Negri-Cesi P, Sacchi MC, Castano P, Colciago A (2014) Platelet derived growth factor (PDGF) contained in platelet rich plasma (PRP) stimulates migration of osteoblasts by reorganizing actin cytoskeleton. Cell Adh Migr 8(6):595–602 Casati L, Celotti F, Negri-Cesi P, Sacchi MC, Castano P, Colciago A (2014) Platelet derived growth factor (PDGF) contained in platelet rich plasma (PRP) stimulates migration of osteoblasts by reorganizing actin cytoskeleton. Cell Adh Migr 8(6):595–602
17.
go back to reference Mariani E, Filardo G, Canella V, Berlingeri A, Bielli A, Cattini L, Landini MP, Kon E, Marcacci M, Facchini A (2014) Platelet-rich plasma affects bacterial growth in vitro. Cytotherapy 16(9):1294–1304CrossRefPubMed Mariani E, Filardo G, Canella V, Berlingeri A, Bielli A, Cattini L, Landini MP, Kon E, Marcacci M, Facchini A (2014) Platelet-rich plasma affects bacterial growth in vitro. Cytotherapy 16(9):1294–1304CrossRefPubMed
18.
go back to reference Mariani E, Canella V, Berlingeri A, Bielli A, Cattini L, Landini MP, Kon E, Marcacci M, Di Matteo B, Filardo G (2015) Leukocyte presence does not increase microbicidal activity of platelet-rich plasma in vitro. BMC Microbiol 15:149 Mariani E, Canella V, Berlingeri A, Bielli A, Cattini L, Landini MP, Kon E, Marcacci M, Di Matteo B, Filardo G (2015) Leukocyte presence does not increase microbicidal activity of platelet-rich plasma in vitro. BMC Microbiol 15:149
19.
go back to reference Arpornmaeklong P, Kochel M, Depprich R, Kübler NR, Würzler KK (2004) Influence of platelet-rich plasma (PRP) on osteogenic differentiation of rat bone marrow stromal cells. An in vitro study. Int J Oral Maxillofac Surg 33(1):60–70CrossRefPubMed Arpornmaeklong P, Kochel M, Depprich R, Kübler NR, Würzler KK (2004) Influence of platelet-rich plasma (PRP) on osteogenic differentiation of rat bone marrow stromal cells. An in vitro study. Int J Oral Maxillofac Surg 33(1):60–70CrossRefPubMed
20.
go back to reference Mooren RE, Hendriks EJ, van den Beucken JJ, Merkx MA, Meijer GJ, Jansen JA, Stoelinga PJ (2010) The effect of platelet-rich plasma in vitro on primary cells: rat osteoblast-like cells and human endothelial cells. Tissue Eng Part A 16(10):3159–3172CrossRefPubMed Mooren RE, Hendriks EJ, van den Beucken JJ, Merkx MA, Meijer GJ, Jansen JA, Stoelinga PJ (2010) The effect of platelet-rich plasma in vitro on primary cells: rat osteoblast-like cells and human endothelial cells. Tissue Eng Part A 16(10):3159–3172CrossRefPubMed
21.
go back to reference Perut F, Filardo G, Mariani E, Cenacchi A, Pratelli L, Devescovi V, Kon E, Marcacci M, Facchini A, Baldini N, Granchi D (2013) Preparation method and growth factor content of platelet concentrate influence the osteogenic differentiation of bone marrow stromal cells. Cytotherapy 15(7):830–839CrossRefPubMed Perut F, Filardo G, Mariani E, Cenacchi A, Pratelli L, Devescovi V, Kon E, Marcacci M, Facchini A, Baldini N, Granchi D (2013) Preparation method and growth factor content of platelet concentrate influence the osteogenic differentiation of bone marrow stromal cells. Cytotherapy 15(7):830–839CrossRefPubMed
22.
go back to reference Hokugo A, Sawada Y, Hokugo R et al (2007) Controlled release of platelet growth factors enhances bone regeneration at rabbit calvaria. Oral Surg, Oral Med, Oral Pathol, Oral Radiol Endod 104(1):44–48CrossRef Hokugo A, Sawada Y, Hokugo R et al (2007) Controlled release of platelet growth factors enhances bone regeneration at rabbit calvaria. Oral Surg, Oral Med, Oral Pathol, Oral Radiol Endod 104(1):44–48CrossRef
23.
go back to reference Sugimori E, Shintani S, Ishikawa K, Hamakawa H (2006) Effects of apatite foam combined with platelet-rich plasma on regeneration of bone defects. Dent Mater J 25(3):591–596CrossRefPubMed Sugimori E, Shintani S, Ishikawa K, Hamakawa H (2006) Effects of apatite foam combined with platelet-rich plasma on regeneration of bone defects. Dent Mater J 25(3):591–596CrossRefPubMed
24.
go back to reference Rai B, Oest ME, Dupont KM, Ho KH, Teoh SH, Guldberg RE (2007) Combination of platelet-rich plasma with polycaprolactone-tricalcium phosphate scaffolds for segmental bone defect repair. J Biomed Mater Res A 81(4):888–899CrossRefPubMed Rai B, Oest ME, Dupont KM, Ho KH, Teoh SH, Guldberg RE (2007) Combination of platelet-rich plasma with polycaprolactone-tricalcium phosphate scaffolds for segmental bone defect repair. J Biomed Mater Res A 81(4):888–899CrossRefPubMed
25.
go back to reference Kasten P, Vogel J, Geiger F, Niemeyer P, Luginbühl R, Szalay K (2008) The effect of platelet-rich plasma on healing in critical-size long-bone defects. Biomaterials 29(29):3983–3992CrossRefPubMed Kasten P, Vogel J, Geiger F, Niemeyer P, Luginbühl R, Szalay K (2008) The effect of platelet-rich plasma on healing in critical-size long-bone defects. Biomaterials 29(29):3983–3992CrossRefPubMed
26.
go back to reference Lysiak-Drwal K, Dominiak M, Solski L, Zywicka B, Pielka S, Konopka T, Gerber H (2008) Early histological evaluation of bone defect healing with and without guided bone regeneration techniques: experimental animal studies. Postepy Hig Med Dosw (Online) 62:282–288 Lysiak-Drwal K, Dominiak M, Solski L, Zywicka B, Pielka S, Konopka T, Gerber H (2008) Early histological evaluation of bone defect healing with and without guided bone regeneration techniques: experimental animal studies. Postepy Hig Med Dosw (Online) 62:282–288
27.
go back to reference Niemeyer P, Fechner K, Milz S, Richter W, Suedkamp NP, Mehlhorn AT, Pearce S, Kasten P (2010) Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma. Biomaterials 31(13):3572–3579CrossRefPubMed Niemeyer P, Fechner K, Milz S, Richter W, Suedkamp NP, Mehlhorn AT, Pearce S, Kasten P (2010) Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma. Biomaterials 31(13):3572–3579CrossRefPubMed
28.
go back to reference Bi L, Cheng W, Fan H, Pei G (2010) Reconstruction of goat tibial defects using an injectable tricalcium phosphate/chitosan in combination with autologous platelet-rich plasma. Biomaterials 31(12):3201–3211CrossRefPubMed Bi L, Cheng W, Fan H, Pei G (2010) Reconstruction of goat tibial defects using an injectable tricalcium phosphate/chitosan in combination with autologous platelet-rich plasma. Biomaterials 31(12):3201–3211CrossRefPubMed
29.
go back to reference Kon E, Filardo G, Delcogliano M, Fini M, Salamanna F, Giavaresi G, Martin I, Marcacci M (2010) Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model. BMC Musculoskelet Disord 11:220CrossRefPubMedPubMedCentral Kon E, Filardo G, Delcogliano M, Fini M, Salamanna F, Giavaresi G, Martin I, Marcacci M (2010) Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model. BMC Musculoskelet Disord 11:220CrossRefPubMedPubMedCentral
30.
go back to reference Kanthan SR, Kavitha G, Addi S, Choon DS, Kamarul T (2011) Platelet-rich plasma (PRP) enhances bone healing in non-united critical-sized defects: a preliminary study involving rabbit models. Injury 42(8):782–789CrossRefPubMed Kanthan SR, Kavitha G, Addi S, Choon DS, Kamarul T (2011) Platelet-rich plasma (PRP) enhances bone healing in non-united critical-sized defects: a preliminary study involving rabbit models. Injury 42(8):782–789CrossRefPubMed
31.
go back to reference Zhang YD, Wang G, Sun Y, Zhang CQ (2011) Combination of platelet-rich plasma with degradable bioactive borate glass for segmental bone defect repair. Acta Orthop Belg 77(1):110–115PubMed Zhang YD, Wang G, Sun Y, Zhang CQ (2011) Combination of platelet-rich plasma with degradable bioactive borate glass for segmental bone defect repair. Acta Orthop Belg 77(1):110–115PubMed
32.
go back to reference Parizi AM, Oryan A, Shafiei-Sarvestani Z, Bigham AS (2012) Human platelet rich plasma plus Persian Gulf coral effects on experimental bone healing in rabbit model: radiological, histological, macroscopical and biomechanical evaluation. J Mater Sci: Mater Med 23(2):473–483 Parizi AM, Oryan A, Shafiei-Sarvestani Z, Bigham AS (2012) Human platelet rich plasma plus Persian Gulf coral effects on experimental bone healing in rabbit model: radiological, histological, macroscopical and biomechanical evaluation. J Mater Sci: Mater Med 23(2):473–483
33.
go back to reference Oryan A, Meimandi Parizi A, Shafiei-Sarvestani Z, Bigham AS (2012) Effects of combined hydroxyapatite and human platelet rich plasma on bone healing in rabbit model: radiological, macroscopical, hidtopathological and biomechanical evaluation. Cell Tissue Bank 13(4):639–651CrossRefPubMed Oryan A, Meimandi Parizi A, Shafiei-Sarvestani Z, Bigham AS (2012) Effects of combined hydroxyapatite and human platelet rich plasma on bone healing in rabbit model: radiological, macroscopical, hidtopathological and biomechanical evaluation. Cell Tissue Bank 13(4):639–651CrossRefPubMed
34.
go back to reference Kasten P, Beverungen M, Lorenz H, Wieland J, Fehr M, Geiger F (2012) Comparison of platelet-rich plasma and VEGF-transfected mesenchymal stem cells on vascularization and bone formation in a critical-size bone defect. Cells Tissues Organs 196(6):523–533CrossRefPubMed Kasten P, Beverungen M, Lorenz H, Wieland J, Fehr M, Geiger F (2012) Comparison of platelet-rich plasma and VEGF-transfected mesenchymal stem cells on vascularization and bone formation in a critical-size bone defect. Cells Tissues Organs 196(6):523–533CrossRefPubMed
35.
go back to reference Kim YH, Furuya H, Tabata Y (2014) Enhancement of bone regeneration by dual release of a macrophage recruitment agent and platelet-rich plasma from gelatin hydrogels. Biomaterials 35(1):214–224CrossRefPubMed Kim YH, Furuya H, Tabata Y (2014) Enhancement of bone regeneration by dual release of a macrophage recruitment agent and platelet-rich plasma from gelatin hydrogels. Biomaterials 35(1):214–224CrossRefPubMed
36.
go back to reference Filardo G, Kon E, Tampieri A, Cabezas-Rodríguez R, Di Martino A, Fini M, Giavaresi G, Lelli M, Martínez-Fernández J, Martini L, Ramírez-Rico J, Salamanna F, Sandri M, Sprio S, Marcacci M (2014) New bio-ceramization processes applied to vegetable hierarchical structures for bone regeneration: an experimental model in sheep. Tissue Eng Part A 20(3–4):763–773PubMed Filardo G, Kon E, Tampieri A, Cabezas-Rodríguez R, Di Martino A, Fini M, Giavaresi G, Lelli M, Martínez-Fernández J, Martini L, Ramírez-Rico J, Salamanna F, Sandri M, Sprio S, Marcacci M (2014) New bio-ceramization processes applied to vegetable hierarchical structures for bone regeneration: an experimental model in sheep. Tissue Eng Part A 20(3–4):763–773PubMed
37.
go back to reference Zhong D, Wang CG, Yin K, Liao Q, Zhou X, Liu AS, Kong LY (2014) In vivo ossification of a scaffold combining β-tricalcium phosphate and platelet-rich plasma. Exp Ther Med 8(5):1381–1388PubMedPubMedCentral Zhong D, Wang CG, Yin K, Liao Q, Zhou X, Liu AS, Kong LY (2014) In vivo ossification of a scaffold combining β-tricalcium phosphate and platelet-rich plasma. Exp Ther Med 8(5):1381–1388PubMedPubMedCentral
38.
go back to reference Chen H, Ji XR, Zhang Q, Tian XZ, Zhang BX, Tang PF (2016) Effects of calcium sulfate combined with platelet-rich plasma on restoration of long bone defect in rabbits. Chin Med J (Engl) 129(5):557–561 Chen H, Ji XR, Zhang Q, Tian XZ, Zhang BX, Tang PF (2016) Effects of calcium sulfate combined with platelet-rich plasma on restoration of long bone defect in rabbits. Chin Med J (Engl) 129(5):557–561
39.
go back to reference Dallari D, Fini M, Stagni C, Torricelli P, Nicoli Aldini N, Giavaresi G, Cenni E, Baldini N, Cenacchi A, Bassi A, Giardino R, Fornasari PM, Giunti A (2006) In vivo study on the healing of bone defects treated with bone marrow stromal cells, platelet-rich plasma, and freeze-dried bone allografts, alone and in combination. J Orthop Res 24(5):877–888CrossRefPubMed Dallari D, Fini M, Stagni C, Torricelli P, Nicoli Aldini N, Giavaresi G, Cenni E, Baldini N, Cenacchi A, Bassi A, Giardino R, Fornasari PM, Giunti A (2006) In vivo study on the healing of bone defects treated with bone marrow stromal cells, platelet-rich plasma, and freeze-dried bone allografts, alone and in combination. J Orthop Res 24(5):877–888CrossRefPubMed
40.
go back to reference Kroese-Deutman HC, Vehof JW, Spauwen PH, Stoelinga PJ, Jansen JA (2008) Orthotopic bone formation in titanium fiber mesh loaded with platelet-rich plasma and placed in segmental defects. Int J Oral Maxillofac Surg 37(6):542–549CrossRefPubMed Kroese-Deutman HC, Vehof JW, Spauwen PH, Stoelinga PJ, Jansen JA (2008) Orthotopic bone formation in titanium fiber mesh loaded with platelet-rich plasma and placed in segmental defects. Int J Oral Maxillofac Surg 37(6):542–549CrossRefPubMed
41.
go back to reference Molina-Miñano F, López-Jornet P, Camacho- Alonso F, Vicente-Ortega V (2009) Plasma rich in growth factors and bone formation: a radiological and histomorphometric study in New Zealand rabbits. Braz Oral Res 23(3):275–280CrossRefPubMed Molina-Miñano F, López-Jornet P, Camacho- Alonso F, Vicente-Ortega V (2009) Plasma rich in growth factors and bone formation: a radiological and histomorphometric study in New Zealand rabbits. Braz Oral Res 23(3):275–280CrossRefPubMed
42.
go back to reference Hakimi M, Jungbluth P, Sager M, Betsch M, Herten M, Becker J, Windolf J, Wild M (2010) Combined use of platelet-rich plasma and autologous bone grafts in the treatment of long bone defects in mini-pigs. Injury 41(7):717–723CrossRefPubMed Hakimi M, Jungbluth P, Sager M, Betsch M, Herten M, Becker J, Windolf J, Wild M (2010) Combined use of platelet-rich plasma and autologous bone grafts in the treatment of long bone defects in mini-pigs. Injury 41(7):717–723CrossRefPubMed
43.
go back to reference Nather A, Wong KL, David V, Pereira BP (2012) Allografts with autogenous platelet-rich plasma for tibial defect reconstruction: a rabbit study. J Orthop Surg (Hong Kong) 20(3):375–380CrossRef Nather A, Wong KL, David V, Pereira BP (2012) Allografts with autogenous platelet-rich plasma for tibial defect reconstruction: a rabbit study. J Orthop Surg (Hong Kong) 20(3):375–380CrossRef
44.
go back to reference Kurikchy MQ, Al-Rawi NH, Ayoub RS, Mohammed SS (2013) Histological evaluation of bone healing using organic bovine bone in combination with platelet-rich plasma (an experimental study on rabbits). Clin Oral Investig 17(3):897–904CrossRefPubMed Kurikchy MQ, Al-Rawi NH, Ayoub RS, Mohammed SS (2013) Histological evaluation of bone healing using organic bovine bone in combination with platelet-rich plasma (an experimental study on rabbits). Clin Oral Investig 17(3):897–904CrossRefPubMed
45.
go back to reference Zhang ZY, Huang AW, Fan JJ, Wei K, Jin D, Chen B, Li D, Bi L, Wang J, Pei G (2013) The potential use of allogeneic platelet-rich plasma for large bone defect treatment: immunogenicity and defect healing efficacy. Cell Transplant 22(1):175–187CrossRefPubMed Zhang ZY, Huang AW, Fan JJ, Wei K, Jin D, Chen B, Li D, Bi L, Wang J, Pei G (2013) The potential use of allogeneic platelet-rich plasma for large bone defect treatment: immunogenicity and defect healing efficacy. Cell Transplant 22(1):175–187CrossRefPubMed
46.
go back to reference Schneppendahl J, Jungbluth P, Lögters TT, Sager M, Wild M, Hakimi M, Windolf J, Grassmann JP (2015) Treatment of a diaphyseal long-bone defect with autologous bone grafts and platelet-rich plasma in a rabbit model. Vet Comp Orthop Traumatol 28(3):164–171CrossRefPubMed Schneppendahl J, Jungbluth P, Lögters TT, Sager M, Wild M, Hakimi M, Windolf J, Grassmann JP (2015) Treatment of a diaphyseal long-bone defect with autologous bone grafts and platelet-rich plasma in a rabbit model. Vet Comp Orthop Traumatol 28(3):164–171CrossRefPubMed
47.
go back to reference Park HC, Kim SG, Oh JS, You JS, Kim JS, Lim SC, Jeong MA, Kim JS, Jung C, Kwon YS, Ji H (2016) Early bone formation at a femur defect using CGF and PRF grafts in adult dogs: a comparative study. Implant Dent 25(3):387–393 Park HC, Kim SG, Oh JS, You JS, Kim JS, Lim SC, Jeong MA, Kim JS, Jung C, Kwon YS, Ji H (2016) Early bone formation at a femur defect using CGF and PRF grafts in adult dogs: a comparative study. Implant Dent 25(3):387–393
48.
go back to reference Rabillard M, Grand JG, Dalibert E, Fellah B, Gauthier O, Niebauer GW (2009) Effects of autologous platelet rich plasma gel and calcium phosphate biomaterials on bone healing in an ulnar ostectomy model in dogs. Vet Comp Orthop Traumatol 22(6):460–466PubMed Rabillard M, Grand JG, Dalibert E, Fellah B, Gauthier O, Niebauer GW (2009) Effects of autologous platelet rich plasma gel and calcium phosphate biomaterials on bone healing in an ulnar ostectomy model in dogs. Vet Comp Orthop Traumatol 22(6):460–466PubMed
49.
go back to reference Jungbluth P, Wild M, Grassmann JP, Ar E, Sager M, Herten M, Jäger M, Becker J, Windolf J, Hakimi M (2010) Platelet-rich plasma on calcium phosphate granules promotes metaphyseal bone healing in mini-pigs. J Orthop Res 28(11):1448–1455CrossRefPubMed Jungbluth P, Wild M, Grassmann JP, Ar E, Sager M, Herten M, Jäger M, Becker J, Windolf J, Hakimi M (2010) Platelet-rich plasma on calcium phosphate granules promotes metaphyseal bone healing in mini-pigs. J Orthop Res 28(11):1448–1455CrossRefPubMed
50.
go back to reference Batista MA, Leivas TP, Rodrigues CJ, Arenas GC, Belitardo DR, Guarniero R (2011) Comparison between the effects of platelet-rich plasma and bone marrow concentrate on defect consolidation in the rabbit tibia. Clinics (Sao Paulo) 66(10):1787–1792 Batista MA, Leivas TP, Rodrigues CJ, Arenas GC, Belitardo DR, Guarniero R (2011) Comparison between the effects of platelet-rich plasma and bone marrow concentrate on defect consolidation in the rabbit tibia. Clinics (Sao Paulo) 66(10):1787–1792
51.
go back to reference Bölükbaşı N, Yeniyol S, Tekkesin MS, Altunatmaz K (2013) The use of platelet-rich fibrin in combination with biphasic calcium phosphate in the treatment of bone defects: a histologic and histomorphometric study. Curr Ther Res Clin Exp 75:15–21CrossRefPubMedPubMedCentral Bölükbaşı N, Yeniyol S, Tekkesin MS, Altunatmaz K (2013) The use of platelet-rich fibrin in combination with biphasic calcium phosphate in the treatment of bone defects: a histologic and histomorphometric study. Curr Ther Res Clin Exp 75:15–21CrossRefPubMedPubMedCentral
52.
go back to reference Hakimi M, Grassmann JP, Betsch M, Schneppendahl J, Gehrmann S, Hakimi AR, Kröpil P, Sager M, Herten M, Wild M, Windolf J, Jungbluth P (2014) The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting. PLoS One 20;9(6):e100143CrossRef Hakimi M, Grassmann JP, Betsch M, Schneppendahl J, Gehrmann S, Hakimi AR, Kröpil P, Sager M, Herten M, Wild M, Windolf J, Jungbluth P (2014) The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting. PLoS One 20;9(6):e100143CrossRef
53.
go back to reference Yilmaz D, Dogan N, Ozkan A, Sencimen M, Ora BE, Mutlu I (2014) Effect of platelet rich fibrin and beta tricalcium phosphate on bone healing. A histological study in pigs. Acta Cir Bras 29(1):59–65CrossRefPubMed Yilmaz D, Dogan N, Ozkan A, Sencimen M, Ora BE, Mutlu I (2014) Effect of platelet rich fibrin and beta tricalcium phosphate on bone healing. A histological study in pigs. Acta Cir Bras 29(1):59–65CrossRefPubMed
54.
go back to reference Malhotra R, Kumar V, Garg B, Singh R, Jain V, Coshic P, Chatterjee K (2015) Role of autologous platelet-rich plasma in treatment of long-bone nonunions: a prospective study. Musculoskelet Surg 99(3):243–248CrossRefPubMed Malhotra R, Kumar V, Garg B, Singh R, Jain V, Coshic P, Chatterjee K (2015) Role of autologous platelet-rich plasma in treatment of long-bone nonunions: a prospective study. Musculoskelet Surg 99(3):243–248CrossRefPubMed
55.
go back to reference Qi Y, Niu L, Zhao T, Shi Z, Di T, Feng G, Li J, Huang Z (2015) Combining mesenchymal stem cell sheets with platelet-rich plasma gel/calcium phosphate particles: a novel strategy to promote bone regeneration. Stem Cell Res Ther 6:256CrossRefPubMedPubMedCentral Qi Y, Niu L, Zhao T, Shi Z, Di T, Feng G, Li J, Huang Z (2015) Combining mesenchymal stem cell sheets with platelet-rich plasma gel/calcium phosphate particles: a novel strategy to promote bone regeneration. Stem Cell Res Ther 6:256CrossRefPubMedPubMedCentral
56.
go back to reference Emilov-Velev K, Clemente-de-Arriba C, Alobera-García MÁ, Moreno-Sansalvador EM, Campo-Loarte J (2015) Bone regeneration in experimental animals using calcium phosphate cement combined with platelet growth factors and human growth hormone. Rev Esp Cir Ortop Traumatol 59(3):200–210PubMed Emilov-Velev K, Clemente-de-Arriba C, Alobera-García MÁ, Moreno-Sansalvador EM, Campo-Loarte J (2015) Bone regeneration in experimental animals using calcium phosphate cement combined with platelet growth factors and human growth hormone. Rev Esp Cir Ortop Traumatol 59(3):200–210PubMed
57.
go back to reference Simman R, Hoffmann A, Bohinc RJ, Peterson WC, Russ AJ (2008) Role of platelet-rich plasma in acceleration of bone fracture healing. Ann Plast Surg 61(3):337–344CrossRefPubMed Simman R, Hoffmann A, Bohinc RJ, Peterson WC, Russ AJ (2008) Role of platelet-rich plasma in acceleration of bone fracture healing. Ann Plast Surg 61(3):337–344CrossRefPubMed
58.
go back to reference Gumieiro EH, Abrahão M, Jahn RS, Segretto H, Alves MT, Nannmark U, Granström G, Dib LL (2010) Platelet-rich plasma in bone repair of irradiated tibiae of Wistar rats. Acta Cirurgica Brasileira 25(3):257–263CrossRefPubMed Gumieiro EH, Abrahão M, Jahn RS, Segretto H, Alves MT, Nannmark U, Granström G, Dib LL (2010) Platelet-rich plasma in bone repair of irradiated tibiae of Wistar rats. Acta Cirurgica Brasileira 25(3):257–263CrossRefPubMed
59.
go back to reference Souza TF, Andrade AL, Ferreira GT, Sakamoto SS, Albuquerque VB, Bonfim SR, Luvizotto MC, Louzada MJ (2012) Healing and expression of growth factors (TGF-ß and PDGF) in canine radial ostectomy gap containing platelet-rich plasma. Vet Comp Orthop Traumatol 25(6):445–452CrossRefPubMed Souza TF, Andrade AL, Ferreira GT, Sakamoto SS, Albuquerque VB, Bonfim SR, Luvizotto MC, Louzada MJ (2012) Healing and expression of growth factors (TGF-ß and PDGF) in canine radial ostectomy gap containing platelet-rich plasma. Vet Comp Orthop Traumatol 25(6):445–452CrossRefPubMed
60.
go back to reference Chen L, Yang X, Huang G, Song D, Ye XS, Xu H, Li W (2013) Platelet-rich plasma promotes healing of osteoporotic fractures. Orthopedics 36(6):e687–e694CrossRefPubMed Chen L, Yang X, Huang G, Song D, Ye XS, Xu H, Li W (2013) Platelet-rich plasma promotes healing of osteoporotic fractures. Orthopedics 36(6):e687–e694CrossRefPubMed
61.
go back to reference Neves PC, Abib Sde C, Neves RF, Pircchio O, Saad KR, Saad PF, Simões RS, Moreira MB, Laurino CF (2013) Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing. Clin (Sao Paulo) 68(9):1239–1246CrossRef Neves PC, Abib Sde C, Neves RF, Pircchio O, Saad KR, Saad PF, Simões RS, Moreira MB, Laurino CF (2013) Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing. Clin (Sao Paulo) 68(9):1239–1246CrossRef
62.
go back to reference Hernandez-Fernandez A, Vélez R, Soldado F, Saenz-Rios JC, Barber I, Aguirre-Canyadell M (2013) Effect of administration of platelet-rich plasma in early phases of distraction osteogenesis: an experimental study in an ovine femur model. Injury 44(7):901–907CrossRefPubMed Hernandez-Fernandez A, Vélez R, Soldado F, Saenz-Rios JC, Barber I, Aguirre-Canyadell M (2013) Effect of administration of platelet-rich plasma in early phases of distraction osteogenesis: an experimental study in an ovine femur model. Injury 44(7):901–907CrossRefPubMed
63.
go back to reference Guzel Y, Karalezli N, Bilge O, Kacira BK, Esen H, Karadag H, Toker S, Göncü RG, Doral MN (2015) The biomechanical and histological effects of platelet-rich plasma on fracture healing. Knee Surg Sports Traumatol Arthrosc 23(5):1378–1383CrossRefPubMed Guzel Y, Karalezli N, Bilge O, Kacira BK, Esen H, Karadag H, Toker S, Göncü RG, Doral MN (2015) The biomechanical and histological effects of platelet-rich plasma on fracture healing. Knee Surg Sports Traumatol Arthrosc 23(5):1378–1383CrossRefPubMed
64.
go back to reference Rodriguez-Collazo ER, Urso ML (2015) Combined use of the Ilizarov method, concentrated bone marrow aspirate (cBMA), and platelet-rich plasma (PRP) to expedite healing of bimalleolar fractures. Strateg Trauma Limb Reconstr 10(3):161–166CrossRef Rodriguez-Collazo ER, Urso ML (2015) Combined use of the Ilizarov method, concentrated bone marrow aspirate (cBMA), and platelet-rich plasma (PRP) to expedite healing of bimalleolar fractures. Strateg Trauma Limb Reconstr 10(3):161–166CrossRef
65.
go back to reference Dallari D, Savarino L, Stagni C, Cenni E, Cenacchi A, Fornasari PM, Albisinni U, Rimondi E, Baldini N, Giunti A (2007) Enhanced tibial osteotomy healing with use of bone grafts supplemented with platelet gel or platelet gel and bone marrow stromal cells. J Bone Joint Surg Am 89(11):2413–2420PubMed Dallari D, Savarino L, Stagni C, Cenni E, Cenacchi A, Fornasari PM, Albisinni U, Rimondi E, Baldini N, Giunti A (2007) Enhanced tibial osteotomy healing with use of bone grafts supplemented with platelet gel or platelet gel and bone marrow stromal cells. J Bone Joint Surg Am 89(11):2413–2420PubMed
66.
go back to reference Peerbooms JC, Colaris JW, Hakkert AA, Van Appeldorn M, Bruijn DJ, Den Oudsten BL, Gosens T (2012) No positive bone healing after using platelet rich plasma in a skeletal defect. An observational prospective cohort study. Int Orthop Oct 36(10):2113–2119CrossRef Peerbooms JC, Colaris JW, Hakkert AA, Van Appeldorn M, Bruijn DJ, Den Oudsten BL, Gosens T (2012) No positive bone healing after using platelet rich plasma in a skeletal defect. An observational prospective cohort study. Int Orthop Oct 36(10):2113–2119CrossRef
67.
go back to reference Lee DH, Ryu KJ, Kim JW, Kang KC, Choi YR (2014) Bone marrow aspirate concentrate and platelet-rich plasma enhanced bone healing in distraction osteogenesis of the tibia. Clin Orthop Relat Res 472(12):3789–3797CrossRefPubMedPubMedCentral Lee DH, Ryu KJ, Kim JW, Kang KC, Choi YR (2014) Bone marrow aspirate concentrate and platelet-rich plasma enhanced bone healing in distraction osteogenesis of the tibia. Clin Orthop Relat Res 472(12):3789–3797CrossRefPubMedPubMedCentral
68.
go back to reference Samy AM (2016) The role of platelet rich plasma in management of fracture neck femur: new insights. Int Orthop 40(5):1019–1024CrossRefPubMed Samy AM (2016) The role of platelet rich plasma in management of fracture neck femur: new insights. Int Orthop 40(5):1019–1024CrossRefPubMed
69.
go back to reference Xavier GL, Achten J, Parsons NR, Costa ML (2013) Platelet-rich therapy in the treatment of patients with hip fractures: a single centre, parallel group, participant-blinded, randomised controlled trial. BMJ Open 3(6). doi:10.1136/bmjopen-2013-002583 Xavier GL, Achten J, Parsons NR, Costa ML (2013) Platelet-rich therapy in the treatment of patients with hip fractures: a single centre, parallel group, participant-blinded, randomised controlled trial. BMJ Open 3(6). doi:10.1136/bmjopen-2013-002583
70.
go back to reference Wei LC, Lei GH, Sheng PY, Gao SG, Xu M, Jiang W, Song Y, Luo W (2012) Efficacy of platelet-rich plasma combined with allograft bone in the management of displaced intra-articular calcaneal fractures: a prospective cohort study. Orthop Res 30(10):1570–1576CrossRef Wei LC, Lei GH, Sheng PY, Gao SG, Xu M, Jiang W, Song Y, Luo W (2012) Efficacy of platelet-rich plasma combined with allograft bone in the management of displaced intra-articular calcaneal fractures: a prospective cohort study. Orthop Res 30(10):1570–1576CrossRef
71.
go back to reference Liebergall M, Schroeder J, Mosheiff R, Gazit Z, Yoram Z, Rasooly L, Daskal A, Khoury A, Weil Y, Beyth S (2013) Stem cell-based therapy for prevention of delayed fracture union: a randomized and prospective preliminary study. Mol Ther 21(8):1631–1638CrossRefPubMedPubMedCentral Liebergall M, Schroeder J, Mosheiff R, Gazit Z, Yoram Z, Rasooly L, Daskal A, Khoury A, Weil Y, Beyth S (2013) Stem cell-based therapy for prevention of delayed fracture union: a randomized and prospective preliminary study. Mol Ther 21(8):1631–1638CrossRefPubMedPubMedCentral
72.
go back to reference Namazi H, Mehbudi A (2016) Investigating the effect of intra-articular PRP injection on pain and function improvement in patients with distal radius fracture. Orthop Traumatol Surg Res 102(1):47–52CrossRefPubMed Namazi H, Mehbudi A (2016) Investigating the effect of intra-articular PRP injection on pain and function improvement in patients with distal radius fracture. Orthop Traumatol Surg Res 102(1):47–52CrossRefPubMed
73.
go back to reference Calori GM, Tagliabue L, Gala L, d’Imporzano M, Peretti G, Albisetti W (2008) Application of rhBMP-7 and platelet-rich plasma in the treatment of long bone non-unions: a prospective randomised clinical study on 120 patients. Injury 39(12):1391–1402CrossRefPubMed Calori GM, Tagliabue L, Gala L, d’Imporzano M, Peretti G, Albisetti W (2008) Application of rhBMP-7 and platelet-rich plasma in the treatment of long bone non-unions: a prospective randomised clinical study on 120 patients. Injury 39(12):1391–1402CrossRefPubMed
74.
go back to reference Calori GM, D’Avino M, Tagliabue L, Albisetti W, d’Imporzano M, Peretti G (2006) An ongoing research for evaluation of treatment with BMPs or AGFs in long bone non-union: protocol description and preliminary results. Injury 37(Suppl 3):S43–S50CrossRefPubMed Calori GM, D’Avino M, Tagliabue L, Albisetti W, d’Imporzano M, Peretti G (2006) An ongoing research for evaluation of treatment with BMPs or AGFs in long bone non-union: protocol description and preliminary results. Injury 37(Suppl 3):S43–S50CrossRefPubMed
75.
go back to reference Tarallo L, Mugnai R, Adani R, Catani F (2012) Treatment of the ulna non-unions using dynamic compression plate fixation, iliac bone grafting and autologous platelet concentrate. Eur J Orthop Surg Traumatol 22(8):681–687. doi:10.1007/s00590-011-0902-y CrossRefPubMed Tarallo L, Mugnai R, Adani R, Catani F (2012) Treatment of the ulna non-unions using dynamic compression plate fixation, iliac bone grafting and autologous platelet concentrate. Eur J Orthop Surg Traumatol 22(8):681–687. doi:10.​1007/​s00590-011-0902-y CrossRefPubMed
76.
go back to reference Mariconda M, Cozzolino F, Cozzolino A, D’Agostino E, Bove A, Milano C (2008) Platelet gel supplementation in long bone nonunions treated by external fixation. J Orthop Trauma 22(5):342–345CrossRefPubMed Mariconda M, Cozzolino F, Cozzolino A, D’Agostino E, Bove A, Milano C (2008) Platelet gel supplementation in long bone nonunions treated by external fixation. J Orthop Trauma 22(5):342–345CrossRefPubMed
77.
go back to reference Say F, Türkeli E, Bülbül M (2014) Is platelet-rich plasma injection an effective choice in cases of non-union? Acta Chir Orthop Traumatol Cech 81(5):340–345PubMed Say F, Türkeli E, Bülbül M (2014) Is platelet-rich plasma injection an effective choice in cases of non-union? Acta Chir Orthop Traumatol Cech 81(5):340–345PubMed
78.
go back to reference Malhotra R, Kumar V, Garg B, Singh R, Jain V, Coshic P, Chatterjee K (2015) Role of autologous platelet-rich plasma in treatment of long-bone nonunions: a prospective study. Musculoskelet Surg 99(3):243–248CrossRefPubMed Malhotra R, Kumar V, Garg B, Singh R, Jain V, Coshic P, Chatterjee K (2015) Role of autologous platelet-rich plasma in treatment of long-bone nonunions: a prospective study. Musculoskelet Surg 99(3):243–248CrossRefPubMed
79.
go back to reference Gołos J, Waliński T, Piekarczyk P, Kwiatkowski K (2014) Results of the use of platelet rich plasma in the treatment of delayed union of long bones.Ortop. Traumatol Rehabil 16(4):397–406CrossRef Gołos J, Waliński T, Piekarczyk P, Kwiatkowski K (2014) Results of the use of platelet rich plasma in the treatment of delayed union of long bones.Ortop. Traumatol Rehabil 16(4):397–406CrossRef
80.
go back to reference Galasso O, Mariconda M, Romano G, Capuano N, Romano L, Iannò B, Milano C (2008) Expandable intramedullary nailing and platelet rich plasma to treat long bone non-unions. J Orthop Traumatol 9(3):129–134CrossRefPubMedPubMedCentral Galasso O, Mariconda M, Romano G, Capuano N, Romano L, Iannò B, Milano C (2008) Expandable intramedullary nailing and platelet rich plasma to treat long bone non-unions. J Orthop Traumatol 9(3):129–134CrossRefPubMedPubMedCentral
81.
go back to reference Sanchez M, Anitua E, Cugat R, Azofra J, Guadilla J, Seijas R, Andia I (2009) Nonunions treated with autologous preparation rich in growth factors. J Orthop Trauma 23(1):52–59CrossRefPubMed Sanchez M, Anitua E, Cugat R, Azofra J, Guadilla J, Seijas R, Andia I (2009) Nonunions treated with autologous preparation rich in growth factors. J Orthop Trauma 23(1):52–59CrossRefPubMed
82.
go back to reference Bielecki T, Gazdzik TS, Szczepanski T (2008) Benefit of percutaneous injection of autologous platelet-leukocyte-rich gel in patients with delayed union and nonunion. Eur Surg Res 40(3):289–296CrossRefPubMed Bielecki T, Gazdzik TS, Szczepanski T (2008) Benefit of percutaneous injection of autologous platelet-leukocyte-rich gel in patients with delayed union and nonunion. Eur Surg Res 40(3):289–296CrossRefPubMed
83.
go back to reference Chiang CC, Su CY, Huang CK, Chen WM, Chen TH, Tzeng YH (2007) Early experience and results of bone graft enriched with autologous platelet gel for recalcitrant nonunions of lower extremity. J Trauma 63(3):655–661CrossRefPubMed Chiang CC, Su CY, Huang CK, Chen WM, Chen TH, Tzeng YH (2007) Early experience and results of bone graft enriched with autologous platelet gel for recalcitrant nonunions of lower extremity. J Trauma 63(3):655–661CrossRefPubMed
84.
85.
go back to reference Filardo G, Di Matteo B, Kon E, Merli G, Marcacci M (2016) Platelet-rich plasma in tendon-related disorders: results and indications. Knee Surg Sports Traumatol Arthrosc. doi:10.1007/s00167-016-4261-4 Filardo G, Di Matteo B, Kon E, Merli G, Marcacci M (2016) Platelet-rich plasma in tendon-related disorders: results and indications. Knee Surg Sports Traumatol Arthrosc. doi:10.​1007/​s00167-016-4261-4
86.
87.
go back to reference Reichert JC, Saifzadeh S, Wullschleger ME, Epari DR, Schütz MA, Duda GN, Schell H, van Griensven M, Redl H, Hutmacher DW (2009) The challenge of establishing preclinical models for segmental bone defect research. Biomaterials 30(12):2149–2163CrossRefPubMed Reichert JC, Saifzadeh S, Wullschleger ME, Epari DR, Schütz MA, Duda GN, Schell H, van Griensven M, Redl H, Hutmacher DW (2009) The challenge of establishing preclinical models for segmental bone defect research. Biomaterials 30(12):2149–2163CrossRefPubMed
88.
go back to reference Gianakos A, Zambrana L, Savage-Elliott I, Lane JM, Kennedy JG (2015) Platelet-rich plasma in the animal long-bone model: an analysis of basic science evidence. Orthopedics 38(12):e1079–e1090 Gianakos A, Zambrana L, Savage-Elliott I, Lane JM, Kennedy JG (2015) Platelet-rich plasma in the animal long-bone model: an analysis of basic science evidence. Orthopedics 38(12):e1079–e1090
89.
go back to reference Tschon M, Fini M, Giardino R, Filardo G, Dallari D, Torricelli P, Martini L, Giavaresi G, Kon E, Maltarello MC, Nicolini A, Carpi A (2011) Lights and shadows concerning platelet products for musculoskeletal regeneration. Front Biosci (Elite Ed) 1(3):96–107 Tschon M, Fini M, Giardino R, Filardo G, Dallari D, Torricelli P, Martini L, Giavaresi G, Kon E, Maltarello MC, Nicolini A, Carpi A (2011) Lights and shadows concerning platelet products for musculoskeletal regeneration. Front Biosci (Elite Ed) 1(3):96–107
90.
go back to reference Weibrich G, Hansen T, Kleis W, Buch R, Hitzler WE (2004) Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration. Bone 34(4):665–671CrossRefPubMed Weibrich G, Hansen T, Kleis W, Buch R, Hitzler WE (2004) Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration. Bone 34(4):665–671CrossRefPubMed
91.
go back to reference Roffi A, Filardo G, Assirelli E, Cavallo C, Cenacchi A, Facchini A, Grigolo B, Kon E, Mariani E, Pratelli L, Pulsatelli L, Marcacci M (2014) Does platelet-rich plasma freeze-thawing influence growth factor release and their effects on chondrocytes and synoviocytes? Biomed Res Int 2014:692913CrossRefPubMedPubMedCentral Roffi A, Filardo G, Assirelli E, Cavallo C, Cenacchi A, Facchini A, Grigolo B, Kon E, Mariani E, Pratelli L, Pulsatelli L, Marcacci M (2014) Does platelet-rich plasma freeze-thawing influence growth factor release and their effects on chondrocytes and synoviocytes? Biomed Res Int 2014:692913CrossRefPubMedPubMedCentral
92.
go back to reference Cavallo C, Roffi A, Grigolo B, Mariani E, Pratelli L, Merli G, Kon E, Marcacci M, Filardo G (2016) Platelet-rich plasma: the choice of activation method affects the release of bioactive molecules. Biomed Res Int 2016:6591717 Cavallo C, Roffi A, Grigolo B, Mariani E, Pratelli L, Merli G, Kon E, Marcacci M, Filardo G (2016) Platelet-rich plasma: the choice of activation method affects the release of bioactive molecules. Biomed Res Int 2016:6591717
93.
go back to reference Dohan Ehrenfest DM, Bielecki T, Jimbo R, Barbé G, Del Corso M, Inchingolo F, Sammartino G (2012) Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF). Curr Pharm Biotechnol 13(7):1145–1152CrossRefPubMed Dohan Ehrenfest DM, Bielecki T, Jimbo R, Barbé G, Del Corso M, Inchingolo F, Sammartino G (2012) Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF). Curr Pharm Biotechnol 13(7):1145–1152CrossRefPubMed
Metadata
Title
Platelet-rich plasma for the treatment of bone defects: from pre-clinical rational to evidence in the clinical practice. A systematic review
Authors
Alice Roffi
Berardo Di Matteo
Gopal Shankar Krishnakumar
Elizaveta Kon
Giuseppe Filardo
Publication date
01-02-2017
Publisher
Springer Berlin Heidelberg
Published in
International Orthopaedics / Issue 2/2017
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-016-3342-9

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