Abstract
Over the past decade, platelet-rich plasma (PRP), a platelet-concentrated plasma fraction, has been widely investigated and applied to regenerative medicine. The clinical utility of PRP is supported by evidence that PRP contains high concentrations of platelet-related growth factors and normal concentrations of plasma-derived fibrinogen, both of which contribute synergistically to the regenerative process. Additionally, its superior cost-efficacy versus conventional therapies is attractive to many clinicians. However, current disadvantages of PRP include a relatively complicated preparation procedure and variable operator-dependent efficacy. An additional disadvantage is the use of bovine thrombin, an animal-derived biological, as a coagulant. Many of these disadvantages are overcome by recent advances in preparation procedures and devices; for example, Joseph Choukroun simplified the platelet-rich fibrin preparation procedure and improved handling efficiency without the aid of animal-derived factors. With advancements in cell processing technology, there has been a general shift in cell therapy from autologous to allogeneic treatment; however, autologous PRP therapy will not easily be replaced by allogeneic treatment in the near future. Therefore, to provide more predictable regenerative therapy outcomes using autologous PRP, further investigations should address developing a standardized procedure for PRP preparation to augment its efficacy and potency, independent of donor variability. We would then propose that operators and clinicians prepare PRP according to the standardized protocol and to carefully evaluate the clinical scenario (i.e., recipient factors comprising skeletal defects) to determine which factor(s) should be added to PRP preparations. This careful approach will lead to improved clinical outcomes for patients.
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References
Okuda K, Kawase T, Momose M, et al. 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. 2003;74:849–57.
Frechette JP, Martineau I, Gagnon G. Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res. 2005;84:434–9.
Weibrich G, Kleis WK, Hafner G. Growth factor levels in the platelet-rich plasma produced by 2 different methods: curasan-type PRP kit versus PCCS PRP system. Int J Oral Maxillofac Implants. 2002;17:184–90.
El-Sharkawy H, Kantarci A, Deady J, et al. Platelet-rich plasma: growth factors and pro- and anti-inflammatory properties. J Periodontol. 2007;78:661–9.
Zhang N, Wu YP, Qian SJ, et al. Research progress in the mechanism of effect of PRP in bone deficiency healing. Sci World J. 2013;2013:134582.
Amable P, Carias RB, Teixeira MV, et al. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. 2013;4:67.
Alsousou J, Ali A, Willett K, Harrison P. The role of platelet-rich plasma in tissue regeneration. Platelets. 2013;24:173–82.
Redler LH, Thompson SA, Hsu SH, Ahmad CS, Levine WN. Platelet-rich plasma therapy: a systematic literature review and evidence for clinical use. Physician Sports Med. 2011;39:42–51.
Naik B, Karunakar P, Jayadev M, Marshal VR. Role of platelet rich fibrin in wound healing: a critical review. J Conserv Dent. 2013;16:284–93.
Burnouf T, Goubran HA, Chen TM, et al. Blood-derived biomaterials and platelet growth factors in regenerative medicine. Blood Rev. 2013;27:77–89.
Stuart JD, Morgan RF, Kenney JG. Single-donor fibrin glue for hand burns. Ann Plast Surg. 1990;24:524–7.
Currie LJ, Sharpe JR, Martin R. The use of fibrin glue in skin grafts and tissue-engineered skin replacements: a review. Plast Reconstr Surg. 2001;108:1713–26.
Marx RE, Carlson ER, Eichstaedt RM, et al. Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontology. 1998;85:638–46.
Kassolis JD, Rosen PS, Reynolds MA. Alveolar ridge and sinus augmentation utilizing platelet-rich plasma in combination with freeze-dried bone allograft: case series. J Periodontol. 2000;71:1654–61.
Robiony M, Polini F, Costa F, Politi M. Osteogenesis distraction and platelet-rich plasma for bone restoration of the severely atrophic mandible: preliminary results. J Oral Maxillofac Surg. 2002;60:630–5.
Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg. 2004;62:489–96.
Alsousou J, Thompson M, Hulley P, Noble A, Willett K. The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery: a review of the literature. J Bone Joint Surg Br. 2009;91:987–96.
Davis VL, Abukabda AB, Radio NM, et al. Platelet-rich preparations to improve healing. Part II: platelet activation and enrichment, leukocyte inclusion, and other selection criteria. J Oral Implantol. 2014;40:511–21.
Lee KS, Wilson JJ, Rabago DP, et al. Musculoskeletal applications of platelet-rich plasma: fad or future? Am J Roentgenol. 2011;196:628–36.
Dohan DM, Choukroun J, Diss A, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontology. 2006;101:e37–44.
Clark RA. Fibrin and wound healing. Ann N Y Acad Sci. 2001;936:355–67.
Xie X, Zhang C, Tuan RS. Biology of platelet-rich plasma and its clinical application in cartilage repair. Arthritis Res Ther. 2014;16:204.
Kawase T, Okuda K, Wolff LF, Yoshie H. Platelet-rich plasma-derived fibrin clot formation stimulates collagen synthesis in periodontal ligament and osteoblastic cells in vitro. J Periodontol. 2003;74:858–64.
Kobayashi M, Kawase T, Horimizu M, et al. A proposed protocol for the standardized preparation of PRF membranes for clinical use. Biologicals. 2012;40:323–9.
Janmey PA, Winer JP, Weisel JW. Fibrin gels and their clinical and bioengineering applications. J R Soc Interface. 2009;6:1–10.
Ryan EA, Mockros LF, Weisel JW, Lorand L. Structural origins of fibrin clot rheology. Biophys J. 1999;77:2813–26.
Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev. 2007;21:131–42.
Perez AG, Rodrigues AA, Luzo AC, et al. Fibrin network architectures in pure platelet-rich plasma as characterized by fiber radius and correlated with clotting time. J Mater Sci Mater Med. 2014;25:1967–77.
Hamid MS, Yusof A, Mohamed Ali AR. Platelet-rich plasma (PRP) for acute muscle injury: a systematic review. PLoS One. 2014;9:e90538.
Wikesjo UM, Sorensen RG, Kinoshita A, Jian Li X, Wozney JM. Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of alveolar bone and periodontal attachment. J Clin Periodontol. 2004;31:662–70.
Selvig KA, Sorensen RG, Wozney JM, Wikesjo UM. Bone repair following recombinant human bone morphogenetic protein-2 stimulated periodontal regeneration. J Periodontol. 2002;73:1020–9.
Murphy KG. Postoperative healing complications associated with Gore-Tex periodontal material. Part I. Incidence and characterization. Int J Periodontics Restor Dent. 1995;15:363–75.
Hitti RA, Kerns DG. Guided bone regeneration in the oral cavity: a review. Open Pathol J. 2011;5:33–45.
Kamionka M. Engineering of therapeutic proteins production in Escherichia coli. Curr Pharm Biotechnol. 2011;12:268–74.
Kiefel V. Reactions induced by platelet transfusions. Transfus Med Hemother. 2008;35:354–8.
Webb CA. Platelet-rich plasma update: clinical use in musculoskeletal care. http://www.rheumatologynetwork.com/articles/platelet-rich-plasma-update-clinical-use-musculoskeletal-care 2012. Accessed 23 Feb 2015.
Marques LF, Stessuk T, Camargo IC, et al. Platelet-rich plasma (PRP): methodological aspects and clinical applications. Platelets. 2015;26:101–13.
Intravia J, Allen DA, Durant TJ, et al. In vitro evaluation of the anti-bacterial effect of two preparations of platelet rich plasma compared with cefazolin and whole blood. Muscles, Ligaments Tendons J. 2014;4:79–84.
Sutter WW. PRP: indications for intra-articular use. https://www.acvs.org/files/proceedings/2011/data/papers/041.pdf. Accessed date 12 Dec 2014.
Wu X, Ren J, Yuan Y, et al. Antimicrobial properties of single-donor-derived, platelet-leukocyte fibrin for fistula occlusion: an in vitro study. Platelets. 2013;24:632–6.
Mariani E, Filardo G, Canella V, et al. Platelet-rich plasma affects bacterial growth in vitro. Cytotherapy. 2014;16:1294–304.
Nakajima Y, Kawase T, Kobayashi M, et al. Bioactivity of freeze-dried platelet-rich plasma in an adsorbed form on a biodegradable polymer material. Platelets. 2012;23:594–603.
Tohidnezhad M, Varoga D, Wruck CJ, et al. Platelets display potent antimicrobial activity and release human beta-defensin 2. Platelets. 2012;23:217–23.
Burnouf T, Chou ML, Wu YW, Su CY, Lee LW. Antimicrobial activity of platelet (PLT)-poor plasma, PLT-rich plasma, PLT gel, and solvent/detergent-treated PLT lysate biomaterials against wound bacteria. Transfusion. 2013;53:138–46.
Anitua E. Plasma rich in growth factors: preliminary results of use in the preparation of future sites for implants. Int J Oral Maxillofac Implants. 1999;14:529–35.
Anitua E. The use of plasma-rich growth factors (PRGF) in oral surgery. Pract Proced Aesthet Dent. 2001;13:487–93.
Anitua E, Sanchez M, Orive G. The importance of understanding what is platelet-rich growth factor (PRGF) and what is not. J Shoulder Elb Surg. 2011;20:e23–4 e4.
Choukroun J. Advanced PRF &i-PRF: platelet concentrates or blood concentrates? J Periodont Med Clin Pract. 2014;1:3.
Ghanaati S, Booms P, Orlowska A, et al. Advanced platelet-rich fibrin (A-PRF)—a new concept for cell-based tissue engineering by means of inflammatory cells. J Oral Implantol. 2014;40(6):679.
Rodella LF, Favero G, Boninsegna R, et al. Growth factors, CD34 positive cells, and fibrin network analysis in concentrated growth factors fraction. Microsc Res Tech. 2011;74:772–7.
Wolkers WF, Walker NJ, Tablin F, Crowe JH. Human platelets loaded with trehalose survive freeze-drying. Cryobiology. 2001;42:79–87.
Crowe JH, Tablin F, Wolkers WF, et al. Stabilization of membranes in human platelets freeze-dried with trehalose. Chem Phys Lipids. 2003;122:41–52.
Brumfiel G. Cell biology: just add water. Nature. 2004;428:14–5.
Pietramaggiori G, Kaipainen A, Czeczuga JM, Wagner CT, Orgill DP. Freeze-dried platelet-rich plasma shows beneficial healing properties in chronic wounds. Wound Repair Regen. 2006;14:573–80.
Sum R, Hager S, Pietramaggiori G, et al. Wound-healing properties of trehalose-stabilized freeze-dried outdated platelets. Transfusion. 2007;47:672–9.
Horimizu M, Kawase T, Nakajima Y, et al. An improved freeze-dried PRP-coated biodegradable material suitable for connective tissue regenerative therapy. Cryobiology. 2013;66:223–32.
Wolff LF. Guided tissue regeneration in periodontal therapy. Northwest Dent. 2000;79(23–8):40.
Bottino MC, Thomas V, Schmidt G, et al. Recent advances in the development of GTR/GBR membranes for periodontal regeneration–a materials perspective. Dent Mater. 2012;28:703–21.
Stoecklin-Wasmer C, Rutjes AW, da Costa BR, et al. Absorbable collagen membranes for periodontal regeneration: a systematic review. J Dent Res. 2013;92:773–81.
Kawase T, Kamiya M, Kobayashi M, et al. The heat-compression technique for the conversion of platelet-rich fibrin preparation to a barrier membrane with a reduced rate of biodegradation. J Biomed Mater Res B Appl Biomater. 2015;103:825–31.
Bieback K. Platelet lysate as replacement for fetal bovine serum in mesenchymal stromal cell cultures. Transfus Med Hemother. 2013;40:326–35.
Shih DT, Burnouf T. Preparation, quality criteria, and properties of human blood platelet lysate supplements for ex vivo stem cell expansion. New Biotechnol. 2015;32:199–211.
Rubio-Azpeitia E, Andia I. Partnership between platelet-rich plasma and mesenchymal stem cells: in vitro experience. Muscles Ligaments Tendons J. 2014;4:52–62.
Robinson SN, Talmadge JE. Sustained release of growth factors. In Vivo (Athens, Greece). 2002;16:535–40.
Yamamoto M, Ikada Y, Tabata Y. Controlled release of growth factors based on biodegradation of gelatin hydrogel. J Biomater Sci Polym Ed. 2001;12:77–88.
Kawase T, Okuda K, Nagata M, Yoshie H. The cell-multilayered periosteal sheet—a promising osteogenic and osteoinductive grafting material. New Trends Tissue Eng Regen Med. Prof. Hideharu Hibi (Ed.). 2014:19–35.
Harmon K, Hanson R, Bowen J, et al. Guidelines for the use of platelet rich plasma. http://www.cellmedicinesociety.org/attachments/206_ICMS%20-%20Guidelines%20for%20the%20use%20of%20Platelet%20Rich%20Plasma%20-%20Draft.pdf. Accessed date 12 Dec 2014.
Acknowledgments
The author expresses special thanks to Prof. Kazuhiro Okuda (Department of Periodontology, Institute of Medicine and Dentistry, Niigata University), Prof. Takaaki Tanaka (Department of Materials Science and Technology, Niigata University), and Prof. Larry F. Wolff (Department of Periodontology, University of Minnesota School of Dentistry) for their helpful comments on this article. This project was financially supported by a Grant-in-Aid for scientific research from JSPS KAKENHI Grant Numbers 24390443 and 24390465.
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Kawase, T. Platelet-rich plasma and its derivatives as promising bioactive materials for regenerative medicine: basic principles and concepts underlying recent advances. Odontology 103, 126–135 (2015). https://doi.org/10.1007/s10266-015-0209-2
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DOI: https://doi.org/10.1007/s10266-015-0209-2