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Biologics in Tendon Healing: PRP/Fibrin/Stem Cells

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The Achilles Tendon

Abstract

Tendon healing entails five essential and overlapping processes, which each has to be mastered and optimized to achieve good patient outcome. These five sequences of tendon repair can be defined as follows: (1) Induction, (2) Production, (3) Orchestration, (4) Conduction and (5) Modification. Biological enhancement of the healing process with novel procedures can be implemented by interaction in different stages of the healing process. Although novel tissue engineering and tissue regenerative techniques addressing tendon repair seem promising, these are not yet ready for routine clinical use. Such methods include molecular approaches by which PRP, PRF, fibrin glue, including stem cells, synthesize growth factors or other mediators needed for progression of failed healing. However, once that the correct indications are known, the correct formulations are understood and the adjuvant treatments during the different healing phases are correctly applied - the future lies in biologics in tendon healing.

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References

  1. Ackermann PW. Healing and repair mechanisms. London: DJO Publications; 2014.

    Google Scholar 

  2. Broughton 2nd G, Janis JE, Attinger CE. Wound healing: an overview. Plast Reconstr Surg. 2006;117(7 Suppl):1e-S–32e-S.

    Article  Google Scholar 

  3. Andia I, Sanchez M, Maffulli N. Tendon healing and platelet-rich plasma therapies. Expert Opin Biol Ther. 10(10):1415–26.

    Google Scholar 

  4. Kaux JF, Drion PV, Colige A, et al. Effects of platelet-rich plasma (PRP) on the healing of Achilles tendons of rats. Wound Repair Regen. 2012;20(5):748–56.

    Article  PubMed  Google Scholar 

  5. Lyras DN, Kazakos K, Verettas D, et al. The influence of platelet-rich plasma on angiogenesis during the early phase of tendon healing. Foot Ankle Int. 2009;30(11):1101–6.

    Article  PubMed  Google Scholar 

  6. Paoloni J, De Vos RJ, Hamilton B, et al. Platelet-rich plasma treatment for ligament and tendon injuries. Clin J Sport Med. 2011;21(1):37–45.

    Article  PubMed  Google Scholar 

  7. Alsousou J, Thompson M, Harrison P, et al. Effect of platelet-rich plasma on healing tissues in acute ruptured Achilles tendon: a human immunohistochemistry study. Lancet. 2015;385 Suppl 1:S19.

    Google Scholar 

  8. 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 Endod. 2006;101(3):e37–44.

    Article  PubMed  Google Scholar 

  9. Zumstein MA, Berger S, Schober M, et al. Leukocyte- and platelet-rich fibrin (L-PRF) for long-term delivery of growth factor in rotator cuff repair: review, preliminary results and future directions. Curr Pharm Biotechnol. 2012;13(7):1196–206.

    Article  CAS  PubMed  Google Scholar 

  10. Dohan Ehrenfest DM, de Peppo GM, Doglioli P, et al. Slow release of growth factors and thrombospondin-1 in Choukroun’s platelet-rich fibrin (PRF): a gold standard to achieve for all surgical platelet concentrates technologies. Growth Factors. 2009;27(1):63–9.

    Article  CAS  PubMed  Google Scholar 

  11. Dietrich F, Duré G L, P Klein C, et al. Platelet-rich fibrin promotes an accelerated healing of Achilles tendon when compared to platelet-rich plasma in rat. World J Plast Surg. 2015;4(2):101–9.

    PubMed  PubMed Central  Google Scholar 

  12. Knobe M, Gradl G, Klos K, et al. Is percutaneous suturing superior to open fibrin gluing in acute Achilles tendon rupture? Int Orthop. 2015;39(3):535–42.

    Article  PubMed  Google Scholar 

  13. Martin P. Wound healing–aiming for perfect skin regeneration. Science (New York). 1997;276(5309):75–81.

    Article  CAS  Google Scholar 

  14. Longo UG, Lamberti A, Maffulli N, et al. Tissue engineered biological augmentation for tendon healing: a systematic review. Br Med Bull. 2011;98:31–59.

    Article  PubMed  Google Scholar 

  15. Tang Y, Leng Q, Xiang X, et al. Use of ultrasound-targeted microbubble destruction to transfect IGF-1 cDNA to enhance the regeneration of rat wounded Achilles tendon in vivo. Gene Ther. 2015;22(8):610–8.

    Article  CAS  PubMed  Google Scholar 

  16. Kurtz CA, Loebig TG, Anderson DD, et al. Insulin-like growth factor I accelerates functional recovery from Achilles tendon injury in a rat model. Am J Sports Med. 1999;27(3):363–9.

    CAS  PubMed  Google Scholar 

  17. Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing. Sports Med. 2003;33(5):381–94.

    Article  PubMed  Google Scholar 

  18. Forslund C, Rueger D, Aspenberg P. A comparative dose-response study of cartilage-derived morphogenetic protein (CDMP)-1, -2 and -3 for tendon healing in rats. J Orthop Res. 2003;21(4):617–21.

    Article  CAS  PubMed  Google Scholar 

  19. Forslund C, Aspenberg P. Improved healing of transected rabbit Achilles tendon after a single injection of cartilage-derived morphogenetic protein-2. Am J Sports Med. 2003;31(4):555–9.

    PubMed  Google Scholar 

  20. Shen H, Gelberman RH, Silva MJ, et al. BMP12 induces tenogenic differentiation of adipose-derived stromal cells. PLoS One. 2013;8(10):e77613.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ackermann PW, Franklin SL, Dean BJ, et al. Neuronal pathways in tendon healing and tendinopathy–update. Front Biosci. 2014;19:1251–78.

    Article  Google Scholar 

  22. Ackermann PW. Neuronal regulation of tendon homoeostasis. Int J Exp Pathol. 2013;94:271–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ackermann PW, Ahmed M, Kreicbergs A. Early nerve regeneration after achilles tendon rupture–a prerequisite for healing? A study in the rat. J Orthop Res. 2002;20(4):849–56.

    Article  PubMed  Google Scholar 

  24. Ackermann PW, Li J, Lundeberg T, et al. Neuronal plasticity in relation to nociception and healing of rat achilles tendon. J Orthop Res. 2003;21(3):432–41.

    Article  PubMed  Google Scholar 

  25. Burssens P, Steyaert A, Forsyth R, et al. Exogenously administered substance P and neutral endopeptidase inhibitors stimulate fibroblast proliferation, angiogenesis and collagen organization during Achilles tendon healing. Foot Ankle Int. 2005;26(10):832–9.

    Article  PubMed  Google Scholar 

  26. Carlsson O, Schizas N, Li J, et al. Substance P injections enhance tissue proliferation and regulate sensory nerve ingrowth in rat tendon repair. Scand J Med Sci Sports. 2011;21(4):562–9.

    Article  CAS  PubMed  Google Scholar 

  27. Steyaert AE, Burssens PJ, Vercruysse CW, et al. The effects of substance P on the biomechanic properties of ruptured rat Achilles’ tendon. Arch Phys Med Rehabil. 2006;87(2):254–8.

    Article  PubMed  Google Scholar 

  28. Nourissat G, Diop A, Maurel N, et al. Mesenchymal stem cell therapy regenerates the native bone-tendon junction after surgical repair in a degenerative rat model. PLoS One. 2010;5(8):e12248.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Okamoto N, Kushida T, Oe K, et al. Treating Achilles tendon rupture in rats with bone-marrow-cell transplantation therapy. J Bone Joint Surg Am. 2010;92(17):2776–84.

    Article  PubMed  Google Scholar 

  30. Ackermann PW, Salo PT, Hart DA. Gene therapy. In: Van Dijk N, Karlsson J, Maffulli N, editors. Achilles tendinopathy current concept. London: DJO Publications; 2010. p. 165–75.

    Google Scholar 

  31. Lee SY, Kim W, Lim C, et al. Treatment of lateral epicondylosis by using allogeneic adipose-derived mesenchymal stem cells: a Pilot Study. Stem Cells. 2015;33(10):2995–3005.

    Article  CAS  PubMed  Google Scholar 

  32. Haegerstrand A, Dalsgaard CJ, Jonzon B, et al. Calcitonin gene-related peptide stimulates proliferation of human endothelial cells. Proc Natl Acad Sci U S A. 1990;87(9):3299–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hong HS, Lee J, Lee E, et al. A new role of substance P as an injury-inducible messenger for mobilization of CD29(+) stromal-like cells. Nat Med. 2009;15(4):425–35.

    Article  CAS  PubMed  Google Scholar 

  34. Legerlotz K, Jones ER, Screen HR, et al. Increased expression of IL-6 family members in tendon pathology. Rheumatology. 2012;51(7):1161–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ackermann PW, Domeij-Arverud E, Leclerc P, et al. Anti-inflammatory cytokine profile in early human tendon repair. Knee Surg Sports Traumatol Arthrosc. 2013;21(8):1801–6.

    Google Scholar 

  36. Andersen MB, Pingel J, Kjaer M, et al. Interleukin-6: a growth factor stimulating collagen synthesis in human tendon. J Appl Physiol. 2011;110(6):1549–54.

    Article  CAS  PubMed  Google Scholar 

  37. Bring D, Reno C, Renstrom P, et al. Prolonged immobilization compromises up-regulation of repair genes after tendon rupture in a rat model. Scand J Med Sci Sports. 2010;20(3):411–7.

    Google Scholar 

  38. Greve K, Domeij-Arverud E, Labruto F, et al. Metabolic activity in early tendon repair can be enhanced by intermittent pneumatic compression. Scand J Med Sci Sports. 2012;22(4):e55–63.

    Article  CAS  PubMed  Google Scholar 

  39. Schizas N, Lian O, Frihagen F, et al. Coexistence of up-regulated NMDA receptor 1 and glutamate on nerves, vessels and transformed tenocytes in tendinopathy. Scand J Med Sci Sports. 2010;20(2):208–15.

    Article  CAS  PubMed  Google Scholar 

  40. Schizas N, Weiss R, Lian O, et al. Glutamate receptors in tendinopathic patients. J Orthop Res. 2012;30(9):1447–52.

    Article  CAS  PubMed  Google Scholar 

  41. Bring DKI, Reno C, Renstrom P, et al. Joint immobilization reduces the expression of sensory neuropeptide receptors and impairs healing after tendon rupture in a rat model. J Orthop Res. 2009;27(2):274–80.

    Article  CAS  PubMed  Google Scholar 

  42. Hou ST, Jiang SX, Smith RA. Permissive and repulsive cues and signalling pathways of axonal outgrowth and regeneration. Int Rev Cell Mol Biol. 2008;267:125–81.

    Article  CAS  PubMed  Google Scholar 

  43. Magnusson SP, Langberg H, Kjaer M. The pathogenesis of tendinopathy: balancing the response to loading. Nat Rev Rheumatol. 2010;6(5):262–8.

    Article  PubMed  Google Scholar 

  44. Gelberman RH, Manske PR, Akeson WH, et al. Flexor tendon repair. J Orthop Res. 1986;4(1):119–28.

    Article  CAS  PubMed  Google Scholar 

  45. Bring DKI, Kreicbergs A, Renstrom PAFH, et al. Physical activity modulates nerve plasticity and stimulates repair after Achilles tendon rupture. J Orthop Res. 2007;25(2):164–72.

    Article  PubMed  Google Scholar 

  46. Schizas N, Li J, Andersson T, et al. Compression therapy promotes proliferative repair during rat Achilles tendon immobilization. J Orthop Res. 2010;28(7):852–8.

    PubMed  Google Scholar 

  47. Kakkos SK, Caprini JA, Geroulakos G, et al. Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism in high-risk patients. Cochrane Database Syst Rev. 2008;4:CD005258.

    Google Scholar 

  48. Khanna A, Gougoulias N, Maffulli N. Intermittent pneumatic compression in fracture and soft-tissue injuries healing. Br Med Bull. 2008;88(1):147–56.

    Article  PubMed  Google Scholar 

  49. Dahl J, Li J, Bring DK, et al. Intermittent pneumatic compression enhances neurovascular ingrowth and tissue proliferation during connective tissue healing: a study in the rat. J Orthop Res. 2007;25(9):1185–92.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Karolinska Institutet, Department of Molecular Medicine and Surgery, SE-17176, Stockholm, Sweden

    Paul W. Ackermann

  2. Department of Orthopaedics and Sports Medicine, Karolinska University Hospital, SE-17176, Stockholm, Sweden

    Paul W. Ackermann

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  1. Paul W. Ackermann
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Correspondence to Paul W. Ackermann .

Editor information

Editors and Affiliations

  1. Center for Hip, Knee and Foot Surgery, ATOS Clinic Centre, Heidelberg, Germany

    Hajo Thermann

  2. Center for Hip, Knee and Foot Surgery, ATOS Clinic Centre, Heidelberg, Germany

    Christoph Becher

  3. Princess Royal Hospital, Telford, Shropshire, United Kingdom

    Michael R. Carmont

  4. Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden

    Jón Karlsson

  5. Department of Medicine and Surgery, University of Salerno, Fisciano, Salerno, Italy

    Nicola Maffulli

  6. Chelsea and Westminster Hospital, London, United Kingdom

    James Calder

  7. Dept of Orthopaedic Surgery, Academic Medical Centre, Amsterdam Zuidoost, The Netherlands

    C. Niek van Dijk

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Ackermann, P.W. (2017). Biologics in Tendon Healing: PRP/Fibrin/Stem Cells. In: Thermann, H., et al. The Achilles Tendon. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-54074-9_23

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  • DOI: https://doi.org/10.1007/978-3-662-54074-9_23

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-54073-2

  • Online ISBN: 978-3-662-54074-9

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