Skip to main content

Advertisement

Log in

Platelet-rich plasma and its derivatives as promising bioactive materials for regenerative medicine: basic principles and concepts underlying recent advances

  • Review Article
  • Published:
Odontology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. 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.

    Article  PubMed  Google Scholar 

  2. Frechette JP, Martineau I, Gagnon G. Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res. 2005;84:434–9.

    Article  PubMed  Google Scholar 

  3. 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.

    PubMed  Google Scholar 

  4. 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.

    Article  PubMed  Google Scholar 

  5. 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.

    Google Scholar 

  6. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Alsousou J, Ali A, Willett K, Harrison P. The role of platelet-rich plasma in tissue regeneration. Platelets. 2013;24:173–82.

    Article  PubMed  Google Scholar 

  8. 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.

    Article  Google Scholar 

  9. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Burnouf T, Goubran HA, Chen TM, et al. Blood-derived biomaterials and platelet growth factors in regenerative medicine. Blood Rev. 2013;27:77–89.

    Article  PubMed  Google Scholar 

  11. Stuart JD, Morgan RF, Kenney JG. Single-donor fibrin glue for hand burns. Ann Plast Surg. 1990;24:524–7.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  Google Scholar 

  13. 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.

    Article  Google Scholar 

  14. 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.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  Google Scholar 

  16. Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg. 2004;62:489–96.

    Article  PubMed  Google Scholar 

  17. 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.

    Article  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. Lee KS, Wilson JJ, Rabago DP, et al. Musculoskeletal applications of platelet-rich plasma: fad or future? Am J Roentgenol. 2011;196:628–36.

    Article  Google Scholar 

  20. 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.

    Article  Google Scholar 

  21. Clark RA. Fibrin and wound healing. Ann N Y Acad Sci. 2001;936:355–67.

    Article  PubMed  Google Scholar 

  22. Xie X, Zhang C, Tuan RS. Biology of platelet-rich plasma and its clinical application in cartilage repair. Arthritis Res Ther. 2014;16:204.

    Article  PubMed Central  PubMed  Google Scholar 

  23. 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.

    Article  PubMed  Google Scholar 

  24. 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.

    Article  PubMed  Google Scholar 

  25. Janmey PA, Winer JP, Weisel JW. Fibrin gels and their clinical and bioengineering applications. J R Soc Interface. 2009;6:1–10.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Ryan EA, Mockros LF, Weisel JW, Lorand L. Structural origins of fibrin clot rheology. Biophys J. 1999;77:2813–26.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev. 2007;21:131–42.

    Article  PubMed  Google Scholar 

  28. 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.

    Article  PubMed  Google Scholar 

  29. Hamid MS, Yusof A, Mohamed Ali AR. Platelet-rich plasma (PRP) for acute muscle injury: a systematic review. PLoS One. 2014;9:e90538.

    Article  PubMed  Google Scholar 

  30. 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.

    Article  PubMed  Google Scholar 

  31. 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.

    Article  PubMed  Google Scholar 

  32. 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.

    Google Scholar 

  33. Hitti RA, Kerns DG. Guided bone regeneration in the oral cavity: a review. Open Pathol J. 2011;5:33–45.

    Article  Google Scholar 

  34. Kamionka M. Engineering of therapeutic proteins production in Escherichia coli. Curr Pharm Biotechnol. 2011;12:268–74.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Kiefel V. Reactions induced by platelet transfusions. Transfus Med Hemother. 2008;35:354–8.

    Article  PubMed Central  PubMed  Google Scholar 

  36. 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.

  37. Marques LF, Stessuk T, Camargo IC, et al. Platelet-rich plasma (PRP): methodological aspects and clinical applications. Platelets. 2015;26:101–13.

    Article  PubMed  Google Scholar 

  38. 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.

    Google Scholar 

  39. Sutter WW. PRP: indications for intra-articular use. https://www.acvs.org/files/proceedings/2011/data/papers/041.pdf. Accessed date 12 Dec 2014.

  40. 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.

    Article  PubMed  Google Scholar 

  41. Mariani E, Filardo G, Canella V, et al. Platelet-rich plasma affects bacterial growth in vitro. Cytotherapy. 2014;16:1294–304.

    Article  PubMed  Google Scholar 

  42. 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.

    Article  PubMed  Google Scholar 

  43. Tohidnezhad M, Varoga D, Wruck CJ, et al. Platelets display potent antimicrobial activity and release human beta-defensin 2. Platelets. 2012;23:217–23.

    Article  PubMed  Google Scholar 

  44. 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.

    Article  PubMed  Google Scholar 

  45. 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.

    PubMed  Google Scholar 

  46. Anitua E. The use of plasma-rich growth factors (PRGF) in oral surgery. Pract Proced Aesthet Dent. 2001;13:487–93.

    PubMed  Google Scholar 

  47. 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.

    Article  Google Scholar 

  48. Choukroun J. Advanced PRF &i-PRF: platelet concentrates or blood concentrates? J Periodont Med Clin Pract. 2014;1:3.

    Google Scholar 

  49. 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.

    Article  PubMed  Google Scholar 

  50. 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.

    Article  PubMed  Google Scholar 

  51. Wolkers WF, Walker NJ, Tablin F, Crowe JH. Human platelets loaded with trehalose survive freeze-drying. Cryobiology. 2001;42:79–87.

    Article  PubMed  Google Scholar 

  52. 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.

    Article  PubMed  Google Scholar 

  53. Brumfiel G. Cell biology: just add water. Nature. 2004;428:14–5.

    Article  PubMed  Google Scholar 

  54. 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.

    Article  PubMed  Google Scholar 

  55. Sum R, Hager S, Pietramaggiori G, et al. Wound-healing properties of trehalose-stabilized freeze-dried outdated platelets. Transfusion. 2007;47:672–9.

    Article  PubMed  Google Scholar 

  56. 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.

    Article  PubMed  Google Scholar 

  57. Wolff LF. Guided tissue regeneration in periodontal therapy. Northwest Dent. 2000;79(23–8):40.

    Google Scholar 

  58. 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.

    Article  PubMed  Google Scholar 

  59. 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.

    Article  PubMed  Google Scholar 

  60. 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.

    Article  PubMed  Google Scholar 

  61. Bieback K. Platelet lysate as replacement for fetal bovine serum in mesenchymal stromal cell cultures. Transfus Med Hemother. 2013;40:326–35.

    Article  PubMed Central  PubMed  Google Scholar 

  62. 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.

    Article  Google Scholar 

  63. 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.

    PubMed Central  PubMed  Google Scholar 

  64. Robinson SN, Talmadge JE. Sustained release of growth factors. In Vivo (Athens, Greece). 2002;16:535–40.

    Google Scholar 

  65. 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.

    Article  PubMed  Google Scholar 

  66. 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.

  67. 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.

Download references

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.

Conflict of interest

The author declares no competing financial interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tomoyuki Kawase.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10266-015-0209-2

Keywords

Navigation