From Platelet-Rich Plasma to Advanced Platelet-Rich Fibrin: Biological Achievements and Clinical Advances in Modern Surgery

Andrea Caruana; Daniele Savina; José Paulo Macedo; Sandra Clara Soares

doi:10.1055/s-0039-1696585

European Journal of Dentistry, Table of Contents

CC BY-NC-ND 4.0 · Eur J Dent 2019; 13(02): 280-286
DOI: 10.1055/s-0039-1696585

Review Article

Dental Investigation Society

From Platelet-Rich Plasma to Advanced Platelet-Rich Fibrin: Biological Achievements and Clinical Advances in Modern Surgery

Andrea Caruana

¹Faculty of Health Sciences, School of Dentistry, Fernando Pessoa University, Porto, Portugal

,

Daniele Savina

¹Faculty of Health Sciences, School of Dentistry, Fernando Pessoa University, Porto, Portugal

,

José Paulo Macedo

¹Faculty of Health Sciences, School of Dentistry, Fernando Pessoa University, Porto, Portugal

,

Sandra Clara Soares

²Biomedical Research Center, Fernando Pessoa Energy, Environment and Health Research Unit, Faculty of Health Sciences, Fernando Pessoa University, Porto, Portugal

› Author Affiliations

Abstract

In the past 20 years, the platelet concentrates have evolved from first-generation products, i.e., platelet-rich plasma (PRP) and plasma rich in growth factors to the second-generation products such as leukocyte-platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF). These autologous products with a higher leukocyte inclusion and flexible fibrin mesh act as a scaffold to increase cellular migration in the angiogenic, osteogenic, and antimicrobial potential of these biomaterials in tissue regeneration. In the second-generation platelet concentrates, the protocols are easier, cheaper, and faster with an entire physiological fibrin matrix, resulting in a tridimensional mesh, not as rigid as one of the first generations. This allows the slow release of molecules over a longer period of time and triggers the healing and regenerative process at the site of injury. The potential of A-PRF to mimic the physiology and immunology of wound healing is also due to the high concentration of growth factors released as follows: vascular endothelial growth factor, platelet-derived growth factor, transforming growth factor-β, and anti-inflammatory cytokines that stimulate tissue cicatrization, vessels formation, and bone cell proliferation and differentiation. Furthermore, the number of neutrophils and monocytes/macrophages is higher releasing important chemotactic molecules such as chemokine ligand-5 and eotaxin. Thus, L-PRF and A-PRF have been used, especially in implantology, periodontology, and maxillofacial surgery. Future clinical applications include tissue regeneration/grafts, ulcers/skin necrosis in the diabetic patient and others, plastic surgery, and even musculoskeletal lesions.

Keywords

advanced platelet-rich fibrin - fibrin - plasma rich in growth factors - platelet concentrates - platelet growth factors - platelet-rich fibrin - platelet-rich plasma - tissue regeneration

Full Text

References

References
1 Dohan DM, Choukroun J, Diss A. et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006a; 101 (03) e45-e50
2 Gupta SJ, Jhingran R, Gupta V, Bains VK, Madan R, Rizvi I. Efficacy of platelet-rich fibrin vs. enamel matrix derivative in the treatment of periodontal intrabony defects: a clinical and cone beam computed tomography study. J Int Acad Periodontol 2014; 16 (03) 86-96
3 Pinto NR, Ubilla M, Zamora Y, Del Rio V, Dohan EhrenfestDM, Quirynen M. Leucocyte- and platelet-rich fibrin (L-PRF) as a regenerative medicine strategy for the treatment of refractory leg ulcers: a prospective cohort study. Platelets 2018; 29 (05) 468-475
4 Anitua E, Sánchez M, Zalduendo MM. et al. Fibroblastic response to treatment with different preparations rich in growth factors. Cell Prolif 2009; 42 (02) 162-170
5 Cabaro S, D'Esposito V, Gasparro R. et al. White cell and platelet content affects the release of bioactive factors in different blood-derived scaffolds. Platelets 2018; 29 (05) 463-467
6 Tatullo M, Marrelli M, Cassetta M. et al. Platelet Rich Fibrin (P.R.F.) in reconstructive surgery of atrophied maxillary bones: clinical and histological evaluations. Int J Med Sci 2012; 9 (10) 872-880
7 Giannini S, Cielo A, Bonanome L. et al. Comparison between PRP, PRGF and PRF: lights and shadows in three similar but different protocols. Eur Rev Med Pharmacol Sci 2015; 19 (06) 927-930
8 Jo CH, Roh YH, Kim JE, Shin S, Yoon KS. Optimizing platelet-rich plasma gel formation by varying time and gravitational forces during centrifugation. J Oral Implantol 2013; 39 (05) 525-532
9 Dhurat R, Sukesh M. Principles and methods of preparation of platelet-rich plasma: a review and author's perspective. J Cutan Aesthet Surg 2014; 7 (04) 189-197
10 Anitua E, Prado R, Sánchez M, Orive G. Platelet-rich plasma: preparation and formulation. Oper Tech Orthop 2012; 22: 25-32
11 Inchingolo F, Tatullo M, Marrelli M. et al. Trial with platelet-rich fibrin and Bio-Oss used as grafting materials in the treatment of the severe maxillar bone atrophy: clinical and radiological evaluations. Eur Rev Med Pharmacol Sci 2010; 14 (12) 1075-1084
12 Jianpeampoolpol B, Phuminart S, Subbalekh K. Platelet-rich fibrin formation was delayed in plastic tubes. BJMMR 2016; 14: 1-9
13 Marrelli M, Tatullo M. Influence of PRF in the healing of bone and gingival tissues. Clinical and histological evaluations. Eur Rev Med Pharmacol Sci 2013; 17 (14) 1958-1962
14 Dohan EhrenfestDM, Del Corso M, Kang BS. et al. The impact of centrifuge characteristics and centrifugation protocols on the cells, growth factors and fibrin architecture of a leukocyte and platelet rich fibrin (L-PRF) clot and membrane. Part 3: comparison of the growth factors content and slow release between the original L-PRF and the modified A-PRF (Advanced Platelet-Rich Fibrin) membranes. Poseido J 2014; 2: 155-166
15 Choukroun J. Advanced PRF and i-PRF: platelet concentrate or blood concentrate?. J Periodontal Med Clin Pract 2014; 1: 1-3
16 Ghanaati S, Booms P, Orlowska A. et al. Advanced platelet-rich fibrin: a new concept for cell-based tissue engineering by means of inflammatory cells. J Oral Implantol 2014; 40 (06) 679-689
17 Anitua E, Sánchez M, Nurden AT, Nurden P, Orive G, Andía I. New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol 2006; 24 (05) 227-234
18 Stellos K, Kopf S, Paul A. et al. Platelets in regeneration. Semin Thromb Hemost 2010; 36 (02) 175-184
19 Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol 2001; 106 (04) 148-156
20 Nör JE, Christensen J, Liu J. et al. Up-regulation of Bcl-2 in microvascular endothelial cells enhances intratumoral angiogenesis and accelerates tumor growth. Cancer Res 2001; 61 (05) 2183-2188
21 Di Alberti L, Rossetto A, Albanese M. et al. Expression of vascular endothelial growth factor (VEGF) mRNA in healthy bone tissue around implants and in peri-implantitis. Minerva Stomatol 2013; 62 (04) (Suppl. 01) 1-7
22 Schmidt MB, Chen EH, Lynch SE. A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair. Osteoarthritis Cartilage 2006; 14 (05) 403-412
23 Caplan AI, Correa D. PDGF in bone formation and regeneration: new insights into a novel mechanism involving MSCs. J Orthop Res 2011; 29 (12) 1795-1803
24 Miyazono K. Positive and negative regulation of TGF-beta signaling. J Cell Sci 2000; 113 (Pt 7): 1101-1109
25 Zhao L, Jiang S, Hantash BM. Transforming growth factor beta1 induces osteogenic differentiation of murine bone marrow stromal cells. Tissue Eng Part A 2010; 16 (02) 725-733
26 Alberto C, De Carvalho RS, Francischone CE, Consolaro MF, Francischone CE. Saucerization of osseointegrated implants and planning of simultaneous orthodontic clinical cases. Dental Press J Orthod 2010; 5: 19-30
27 Kurten RC, Chowdhury P, Sanders Jr RC. et al. Coordinating epidermal growth factor-induced motility promotes efficient wound closure. Am J Physiol Cell Physiol 2005; 288 (01) C109-C121
28 Govoni KE. Insulin-like growth factor-I molecular pathways in osteoblasts: potential targets for pharmacological manipulation. Curr Mol Pharmacol 2012; 5 (02) 143-152
29 Kawazoe T, Kim HH. Tissue augmentation by white blood cell-containing platelet-rich plasma. Cell Transplant 2012; 21 (02) (03) 601-607
30 Dohan EhrenfestDM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol 2009; 27 (03) 158-167
31 Dohan EhrenfestDM, Del Corso M, Inchingolo F, Sammartino G, Charrier JB. Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in human cell cultures: growth factor release and contradictory results. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 110 (04) 418-421 , author reply 421–422
32 Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 2004; 91 (01) 4-15
33 Anitua E, Sánchez M, Orive G, Andía I. The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. Biomaterials 2007; 28 (31) 4551-4560
34 Li Q, Pan S, Dangaria SJ. et al. Platelet-rich fibrin promotes periodontal regeneration and enhances alveolar bone augmentation. BioMed Res Int 2013; 2013: 638043
35 Kumar RV, Shubhashini N. Platelet rich fibrin: a new paradigm in periodontal regeneration. Cell Tissue Bank 2013; 14 (03) 453-463
36 Arosa F, Cardoso E, Pacheco F. Immunology Fundamentals. 2nd ed.. Lisbon: Lidel Technical Editions Limited; 2012
37 Dohan DM, Choukroun J, Diss A. et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates?. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006b; 101 (03) e51-e55
38 Hart J. Inflammation. 1: Its role in the healing of acute wounds. J Wound Care 2002; 11 (06) 205-209
39 Di Liddo R, Bertalot T, Borean A. et al. Leucocyte and platelet-rich fibrin: a carrier of autologous multipotent cells for regenerative medicine. J Cell Mol Med 2018; 22 (03) 1840-1854
40 Dohan EhrenfestDM, Bielecki T, Jimbo R. et al. 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 2012; 13 (07) 1145-1152
41 Zafar MS, Khurshid Z, Almas K. Oral tissue engineering progress and challenges. Tissue Eng Regen Med 2015; 12: 387-397
42 Aggour RL, Abd El-HadyHM. Platelet-rich fibrin for the treatment of intrabony periodontal defects in patients with generalized aggressive periodontitis: A randomized controlled clinical study. J Int Acad Periodontol 2017; 19: 28-34
43 Kobayashi E, Flückiger L, Fujioka-Kobayashi M. et al. Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig 2016; 20 (09) 2353-2360
44 Marrelli M, Paduano F, Tatullo M. Human periapical cyst-mesenchymal stem cells differentiate into neuronal cells. J Dent Res 2015; 94 (06) 843-852
45 van Hinsbergh VW, Collen A, Koolwijk P. Role of fibrin matrix in angiogenesis. Ann N Y Acad Sci 2001; 936: 426-437
46 Del Corso M, Vervelle A, Simonpieri A. et al. 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 2012; 13 (07) 1207-1230
47 Miron RJ, Zucchelli G, Pikos MA. et al. Use of platelet-rich fibrin in regenerative dentistry: a systematic review. Clin Oral Investig 2017; 21 (06) 1913-1927
48 Najeeb S, Khurshid Z, Agwan MAS, Ansari SA, Zafar MS, Matinlinna JP. Regenerative potential of platelet rich fibrin (PRF) for curing intrabony periodontal defects: a systematic review of clinical studies. Tissue Eng Regen Med 2017; 14 (06) 735-742
49 Maluf G, Caldas RJ, Silva SantosPS. Use of leukocyte – and platelet-rich fibrin in the treatment of medication-related osteonecrosis of the jaws. J Oral Maxillofac Surg 2018; 76 (01) 88-96
50 Masoudi E, Ribas J, Kaushik G, Leijten J, Khademhosseini A. Platelet-rich blood derivatives for stem cell-based tissue engineering and regeneration. Curr Stem Cell Rep 2016; 2 (01) 33-42
51 Dohan EhrenfestDM, Pinto NR, Pereda A. et al. The impact of the centrifuge characteristics and centrifugation protocols on the cells, growth factors, and fibrin architecture of a leukocyte- and platelet-rich fibrin (L-PRF) clot and membrane. Platelets 2018; 29 (02) 171-184
52 Rock L. Potential of platelet rich fibrin in regenerative periodontal therapy: Literature review. Can J Dent Hyg 2013; 47: 33-37
53 Del Corso M, Mazor Z, Rutkowski JL, Dohan EhrenfestDM. The use of leukocyte- and platelet-rich fibrin during immediate postextractive implantation and loading for the esthetic replacement of a fractured maxillary central incisor. J Oral Implantol 2012; 38 (02) 181-187
54 Clark D, Rajendran Y, Paydar S. et al. Advanced platelet-rich fibrin and freeze-dried bone allograft for ridge preservation: a randomized controlled clinical trial. J Periodontol 2018; 89 (04) 379-387
55 ClinicalTrials.gov National Library of Medicine (U.S.). Advanced Platelet Rich Fibrin in Periodontal Angular Defects. Identifier NCT03433066; 2018 Available at: https://www.clinicaltrials.gov/ct2/show/NCT03433066 . Accessed December 19, 2018
56 Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 2011; 11 (06) 471-491
57 Crisci A, Marotta G, Licito A, Serra E, Benincasa G, Crisci M. Use of leukocyte platelet (L-PRF) rich fibrin in diabetic foot ulcer with osteomyelitis (Three clinical cases report). Diseases 2018; 6 (02) E30