Skip to main content

Advertisement

SpringerLink
Log in

Platelet-Rich Therapies in the Treatment of Orthopaedic Sport Injuries

  • Leading Article
  • Published:
Sports Medicine Aims and scope Submit manuscript

Abstract

Biomedical sciences have made major advances in understanding how tissues repair, and the signalling mechanisms required to achieve this goal are progressively being dissected. Advances in the understanding of tissue repair mechanisms and the pivotal role of growth factors have stimulated the use of platelet-rich therapies by orthopaedic surgeons and sports physicians, mainly with the aim of stimulating and enhancing tissue healing. Autologous activated platelets retained in fibrin matrices are used as a source of molecular signals that control cell fate, including cell growth, cell differentiation and the synthesis of diverse functional proteins. Thus far, platelet-rich technologies have spawned additional ambitious endeavours, including surgical and nonsurgical treatments in sports orthopaedics. Reconstruction of anterior cruciate ligament and tendon surgery and treatment of joint injuries, tendinopathy or muscle tears are but a few examples of the potential applications of this technology in the field of orthopaedic sports medicine. In the present article, some of the most important therapeutic applications using these approaches–especially preparation rich in growth factor (PRGF) technology–are presented, as are some of the limitations, anti-doping concerns and future challenges in the field. In view of a general state of confusion, the concept of platelet-rich plasma needs rigorous definition associated with well characterized products and re-administration procedures. There is evidence that reconstruction of anterior cruciate ligament and tendon surgery combined with PRGF enhances healing and functional recovery; clinical evidence is also appearing in the literature regarding treatment of tendinopathies and osteoarthritis. Currently, the challenge lies in conducting randomized, controlled clinical trials to determine the essential qualities of these technologies. If anti-doping agencies clarify their regulatory guidelines, robust studies in athletes are expected to emerge. Although much research work lies ahead, the current knowledge points to a future in which platelet-rich therapies will continue improving existing conventional approaches to treatment of sports injuries.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Cassel EP, Finch CF, Stathakis VZ. Epidemiology of medically treated sport and active recreation injuries in the Latrobe Valley, Victoria, Australia. Br J Sports Med 2003; 37: 405–9

    Article  Google Scholar 

  2. Fanelli GC, Orcutt DR, Harris JD. The athletically active middle aged arthritic knee: introduction, demographics, sports participation epidemiology and types of injuriesseen. Sports Med Arthroscop Rev 2003; 11 (2): 98–101

    Article  Google Scholar 

  3. Timpka T, Ekstrand J, Svanström L. From sports injury prevention to safety promotion in sports. Sports Med 2006; 36 (9): 733–45

    Article  PubMed  Google Scholar 

  4. Fredericson M, Misra AK. Epidemiology and aetiology of marathon running injuries. Sports Med 2007; 37: 437–9

    Article  PubMed  Google Scholar 

  5. Goldber AS, Moroz L, Smith A, et al. Injury surveillance in young athletes. Sports Med 2007; 37: 265–78

    Article  Google Scholar 

  6. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev 2003; 83: 835–70

    PubMed  CAS  Google Scholar 

  7. Langer R, Tirell DA. Designing materials for biology and medicine. Nature 2004; 428: 487–92

    Article  PubMed  CAS  Google Scholar 

  8. Tabata Y. Tissue regeneration based on growth factor release. Tissue Eng 2003; 9: S5–15

    Article  Google Scholar 

  9. Anitua E, Sanchez M, Nurden AT, et al. New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol 2006; 24: 227–34

    Article  PubMed  CAS  Google Scholar 

  10. Anitua E, Sánchez M, Orive G, et al. Therapeutic applications of the preparation rich in growth factors (PRGF). In:Jie Hu, editor. Recent advances in biomaterial research. Kerala: Transworld Research Network, 2008: 141–53

    Google Scholar 

  11. Kajikawa Y, Morihara T, Sakamoto H, et al. Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing. J Cell Physiol 2008; 59: 1329–39

    Google Scholar 

  12. Hoffman A, Gross G. Tendon and ligament engineering in the adult organism: mesenchymal stem cells and gene-therapeutic approaches. Int Orthop 2007; 31: 791–7

    Article  Google Scholar 

  13. Rehfeldt F, Engler AJ, Eckardt A, et al. Cell responses to the mechanochemical microenvironment: implications for regenerative medicine and drug delivery. Adv Drug Deliv Rev 2007; 59: 1329–39

    Article  PubMed  CAS  Google Scholar 

  14. Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet derived growth factor. Physiol Rev 1999; 79 (4): 1283–316

    PubMed  CAS  Google Scholar 

  15. Shi Y, Massague J. Mechanisms of TGF-beta signalling from cell membrane to the nucleus. Cell 2003; 113 (6): 685–700

    Article  PubMed  CAS  Google Scholar 

  16. Danielpour D, Song K. Cross-talk between IGF-I and TGF-beta signaling pathways. Cytokine Growth Factor Rev 2006; 17: 59–74

    Article  PubMed  CAS  Google Scholar 

  17. Gerritsen ME, Tomlinson JE, Zlot C, et al. Using gene expression profiling to identify the molecular basis of the synergistic actions of hepatocyte growth factor and vascular endothelial growth factor in human endothelial cells. Br J Pharmacol 2003; 140: 595-10

    Article  PubMed  CAS  Google Scholar 

  18. Gianchandani EP, Brautigan DL, Papin JA. Systems analyses characterize integrated functions of biochemical networks. Trends Biochem Sci 2006; 31: 284–91

    Article  PubMed  CAS  Google Scholar 

  19. Aspenberg P. Stimulation of tendon repair: mechanical loading, GDFs and platelets. A mini-review. Acta Orthop 2007; 31 (6): 783–9

    Google Scholar 

  20. Gibble J, Ness P. Fibrin glue: the perfect operative sealant? Transfusion 1990; 30: 741–7

    Article  PubMed  CAS  Google Scholar 

  21. Whitman DH, Berry RL, Green DM. Platelet gel: an autologous alternative to fibrin glue with applications in oral and maxillofacial surgery. J Oral Maxillofac Surg 1997; 55 (11): 1294–99

    Article  PubMed  CAS  Google Scholar 

  22. Anitua E. Plasma rich in growth factors: preliminary results of the use in the preparation of future sites for implants. Int J Oral Maxillofac Implants 1999; 14: 529–35

    PubMed  CAS  Google Scholar 

  23. Marx RE, Carlson ER, Eichstaedt RN, et al. Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endodon 1998; 85: 638–46

    Article  CAS  Google Scholar 

  24. 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  CAS  Google Scholar 

  25. Bielecki TM, Gazdzik TS, Arendt J, et al. Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances. J Bone Joint Surg 2007; 89: 417–20

    Article  CAS  Google Scholar 

  26. Anitua E, Andía I, Ardanza B, et al. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 2004; 91: 4–15

    PubMed  CAS  Google Scholar 

  27. Nurden AT, Nurden P, Sanchez M, et al. Platelet and wound healing. Front Biosci 2008; 13: 3532–48

    PubMed  Google Scholar 

  28. Laurens N, Koolwijk P, De Maat MPM. Fibrin structure and wound healing. J Thromb Haemost 2006; 4: 932–9

    Article  PubMed  CAS  Google Scholar 

  29. Asfaha S, Cena N, Houl S, et al. Protease-activated receptor-4: a novel mechanism of inflammatory pain modulation. Br J Pharmacol 2006; 150: 176–85

    Article  PubMed  Google Scholar 

  30. Trowbridge CC, Stammers AH, Woods E, et al. Use of platelet gel and its effects on infection in cardiac surgery. J Extra Corpor Technol 2005; 37 (4): 381–6

    PubMed  Google Scholar 

  31. Tang YQ, Yeaman MR, Selsted ME. Antimicrobial peptides from human platelets. Infect Immun 2002; 70: 6515–7

    Article  Google Scholar 

  32. Everts AM, Zundert AV, Schönberger JPAM, et al. What do we use: platelet-rich plasma or platelet leukocyte gel? J Biomed Mat Res A 2008; 85: 1135–6

    Article  Google Scholar 

  33. Bramono DS, Richmond JC, Weitzel PI, et al. Matrix metalloproteinases and their clinical applications in orthopaedics. Clin Orthop Relat Res 2004; 428: 272–85

    Article  PubMed  Google Scholar 

  34. Tidball JG. Inflammatory cell response to acute muscle injury. Med Sci Sports Exerc 1995; 27: 1022–32

    Article  PubMed  CAS  Google Scholar 

  35. Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol 2005; 288: R345–53

    Article  Google Scholar 

  36. Pizza FX, McLoughlin TJ, McGregor SJ, et al. Neutrophils injured cultured skeletal myotubes. Am J Physiol Cell Physiol 2001; 281: C353–41

    Google Scholar 

  37. Schneider BP, Tiidus PM. Neutrophil infiltration in exercise injured skeletal muscle. Sports Med 2007; 37 (10): 837–56

    Article  PubMed  Google Scholar 

  38. Veillet CJ, McKee MD. Growth factors-BMPs, DBMs, and buffy coat products: are there any proven differences amongst them? Injury Int J Care Injured 2007; 38 Suppl. 1: S38–48

    Google Scholar 

  39. Anitua E, Sánchez M, Orive G, et al. Shedding light in the controversial terminology for platelet rich products. J Biomed Mat Res A. In press

  40. Anitua E, Sanchez M, Orive G, et al. Delivering growth factors for therapeutics. Trends Pharmacol Sci 2008; 29 (1): 37–41

    Article  PubMed  CAS  Google Scholar 

  41. Anitua E, Aguirre JJ, Algorta J, et al. Effectiveness of autologous preparation rich in growth factors for the treatment of chronic cutaneous ulcers. J Biomed Mater Res B: Appl Biomater 2008; 84B: 415–21

    Article  CAS  Google Scholar 

  42. Anitua E, Sanchez M, Orive G, et al. The potential impact of the preparations rich in growth factors (PRGF) in different medical fields. Biomaterials 2007; 28: 4551–60

    Article  PubMed  CAS  Google Scholar 

  43. Creaney L, Hamilton B. Growth factor delivery methods in the management of sports injuries: the state of the play. Br J Sports Med 2008; 42: 314–20

    Article  PubMed  CAS  Google Scholar 

  44. Molloy T, Wang Y, Murrell GAC. The roles of growth factors in tendon and ligament healing. Sports Med 2003; 33: 381–94

    Article  PubMed  Google Scholar 

  45. Anitua E, Andia I, Sanchez M, et al. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture. J Orthop Res 2005; 23: 281–6

    Article  PubMed  CAS  Google Scholar 

  46. Conway K, Price P, Harding KG, et al. The molecular and clinical impact of hepatocyte growth factor, its receptors, activators, and inhibitors in wound healing. Wound Rep Reg 2006; 14: 2–10

    Article  Google Scholar 

  47. Anitua E, Sanchez M, Nurden AT, et al. Autologous fibrin matrices: a potential source of biological mediators that modulate tendon cell activities. J Biomed Mat Res A 2006; 77: 285–93

    Article  Google Scholar 

  48. Anitua E, Sanchez M, Nurden AT, et al. Reciprocal actions of platelet-secreted TGF-beta1 on the production ofVEGF and HGF by human tendon cells. Plast Reconstr Surg 2007; 119: 950–9

    Article  PubMed  CAS  Google Scholar 

  49. Virchenko O, Aspenberg P. How can one platelet injection after tendon injury lead to a stronger tendon after 4 weeks? Interplay between early regeneration and mechanical stimulation. Acta Orthop 2006; 77 (5): 806–12

    Google Scholar 

  50. Sanchez M, Anitua E, Azofra J, et al. Comparison of surgically repaired Achilles tendon tears using PRGF. Am J Sports Med 2007; 35 (2): 245–51

    Article  PubMed  Google Scholar 

  51. Peers KH, Lysens RJ. Patellar tendinopathy in athletes. Sports Med 2005; 35 (1): 71–87

    Article  PubMed  Google Scholar 

  52. Field LD, Savoie FH. Common elbow injuries in sport. Sports Med 1998; 26 (3): 193–205

    Article  PubMed  CAS  Google Scholar 

  53. Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med 2006; 34 (11): 1774–8

    Article  PubMed  Google Scholar 

  54. Suresh SPS, Ali KE, Jones H, et al. Medial epicondylitis: is ultrasound guided autologous blood injection an effective treatment? Br J Sports Med 2006; 40: 935–9

    Article  PubMed  CAS  Google Scholar 

  55. Griffin LY. Noncontact anterior cruciate ligament injuries: risk factors and prevention strategies. J Am Acad Orthop Surg 2008; 8: 141–50

    Google Scholar 

  56. Johnson DL, Urban Jr WP, et al. Articular cartilage changes seen with magnetic resonance imaging detected bone bruises associated with acute anterior cruciate ligament rupture. Am J Sports Med 1998; 26 (3): 409–14

    PubMed  CAS  Google Scholar 

  57. Brown CH, Carson EW. Revision anterior cruciate ligament surgery. Clin Sports Med 1999; 18: 109–17

    Article  PubMed  Google Scholar 

  58. Pennisi E. Tending tender tendons. Science 2002; 295: 1011

    Article  PubMed  CAS  Google Scholar 

  59. Vunjak-Novakovic G, Altman G, Horan R, et al. Tissue engineering of ligaments. Ann Rev Biomed Eng 2004; 6: 131–56

    Article  CAS  Google Scholar 

  60. Murray MM, Spindler KP, Devin C, et al. Use of a collagen platelet rich plasma scaffold to stimulate healing of a central defect in the canine ACL. J Orthop Res 2006; 24 (4): 820–30

    Article  PubMed  CAS  Google Scholar 

  61. Sánchez M, Azofra J, Aizpurua B, et al. Use of autologous plasma rich in growth factors in arthroscopic surgery. Cuadernos Artroscop 2003; 10: 12–9

    Google Scholar 

  62. Sánchez M, Azofra J, Anitua E, et al. Plasma rich in growth factors to treat an articular cartilage avulsion: a case report. Med Sci Sports Exerc 2003; 35: 1648–52

    Article  PubMed  Google Scholar 

  63. Cugat R, Carrillo JM, Serra I, et al. Articular cartilage defects reconstruction by plasma rich in growth factors. In: Zanasi S, Brittberg M, Marcacci M, editors. Basic science, clinical repair and reconstruction of articular cartilage defects: current status and prospects. Bologna: Timeo Editore, 2006: 801–7

    Google Scholar 

  64. Akeda K, An HS, Okuma M, et al. Platelet-rich plasma stimulates porcine articular chondrocyte proliferation and matrix biosynthesis. Osteoarthritis Cartilage 2007; 14: 1272–80

    Article  Google Scholar 

  65. Ishida K, Kuroda R, Miwa M, et al. The regenerative effects of platelet-rich plasma on meniscal cells in vitro and itsin vivo application with biodegradable gelatin hydrogel. Tissue Eng 2007; 13 (5): 1103–12

    Article  PubMed  CAS  Google Scholar 

  66. Rall K, McElroy G, Keats TE. A study of the long-term effects of football injury in the knee. Mol Med 1984; 61: 435–38

    Google Scholar 

  67. Shephard GJ, Banks AJ, Ryan WG. Ex-professional association footballers have an increased prevalence of osteoarthritis of the hip compared with age-matched controls despite not having sustained notable hip injuries. Br J Sports Med 2003; 37: 80–1

    Article  Google Scholar 

  68. Anitua E, Sanchez M, Nurden AT, et al. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients. Rheumatology 2007; 46: 1769–72

    Article  PubMed  CAS  Google Scholar 

  69. Anitua E, Sanchez M, Azofra J, et al. Autologous preparation rich in growth factors for treating knee osteoarthritis: clinical-biological study [abstract]. World congress on osteoarthritis: osteoarthritis cartilage; 2007 Dec; Fort Lauderdale (FL), 15 Suppl. C: 6–9 C218

    Google Scholar 

  70. Sanchez M, Anitua E, Azofra J, et al. Clinical benefits of using an autologous preparation rich in growth factors to treat knee osteoarthritis [abstract]. World congresson osteoarthritis: osteoarthritis cartilage; 2007 Dec; Fort Lauderdale (FL), 15 Suppl. C: 6–9 C148

    Google Scholar 

  71. Sánchez M, Anitua E, Azofra J, et al. Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. Clin Exp Rheumatol 2008; 26: 910–3

    PubMed  Google Scholar 

  72. Sanchez M, Anitua E, Andia I. Application of autologous growth factors on skeletal muscle healing [oral presentation]. 2nd International Conference on regenerative medicine 2005 [online]. Available from URL: http://regmed2005.abstract-management.De/overview/?ID=314 [Accessed 2008 Jan 8]

    Google Scholar 

  73. World Anti-Doping Agency [online]. Available from URL: http://www.wada-ama.org [Accessed 2008 Mar 16]

  74. Denley A, Cosgrove LJ, Booker GW, et al. Molecular interactions of the IGF system. Cytokine Growth Factor Rev 2005; 16: 421–39

    Article  PubMed  CAS  Google Scholar 

  75. Olesen JL, Heinemeier KM, Langberg H, et al. Expression, content and localization of insulin-like growth factor I in human Achilles tendon. Connect Tissue Rep 2006; 47: 200–6

    Article  CAS  Google Scholar 

  76. Wildemann B, Kadow-Romacker A, Pruss A, et al. Quantification of growth factors in allogenic bone grafts extracted with three different methods. Cell Tissue Bank 2007; 8 (2): 104–14

    Article  Google Scholar 

Download references

Acknowledgements

The research of this group is partially funded by the Basque and Spanish Governments.

Eduardo Anitua, Gorka Orive and Isabel Andia work in the Research Department of the Biotechnology Institute, a dental implant company that markets a system for preparing PRP for therapeutic use.

Author information

Authors and Affiliations

  1. Unidad de Cirugía Artroscópica “Mikel Sánchez”, La Esperanza, Vitoria, Spain

    Mikel Sánchez

  2. Biotechnology Institute IMASD, San Antonio, Vitoria, Spain

    Eduardo Anitua, Gorka Orive &  Isabel Andia

  3. USP Araba Sport Clinic, Vitoria, Spain

    Iñigo Mujika

Authors
  1. Mikel Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eduardo Anitua
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gorka Orive
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Iñigo Mujika
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isabel Andia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isabel Andia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sánchez, M., Anitua, E., Orive, G. et al. Platelet-Rich Therapies in the Treatment of Orthopaedic Sport Injuries. Sports Med 39, 345–354 (2009). https://doi.org/10.2165/00007256-200939050-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00007256-200939050-00002

Keywords

Search

Navigation