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Biologics in the Foot and Ankle

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Sports Injuries of the Foot and Ankle

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Abstract

Tendon injuries are common in sports and can be difficult to treat. Tendon injuries account for 30% of the $30 billion spent every year on musculoskeletal injuries in the USA alone [1, 2]. While observing U.S. Division I collegiate athletes participating in 37 sports, Raikin, Garras, and Krapchev found that foot and ankle injuries accounted for 27% of all musculoskeletal injuries [3]. Basketball, in particular, has a relatively high incidence of tendon injuries compared to other sports [4]. Lievers et al. examined the rate of foot and ankle injuries in collegiate American football and found that the rate of foot and ankle injuries was 15 per 10,000 athletic sessions [5]. In tendon healing, primary healing is prolonged and recurrence rates as high as 30% have been reported [6–8]. Given the high cost of foot and ankle injuries, it is important to understand the current challenges facing the treatment of tendon injuries, as well as identify optimal treatment strategies for rehabilitating athletes effectively.

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References

  1. Padilla S, Sánchez M, Orive G, Anitua E. Human-based biological and biomimetic autologous therapies for musculoskeletal tissue regeneration. Trends Biotechnol [Internet]. 2017;35(3):192–202. https://doi.org/10.1016/j.tibtech.2016.09.008.

    Article  CAS  Google Scholar 

  2. Nourissat G, Berenbaum F, Duprez D. Tendon injury: from biology to tendon repair. Nat Rev Rheumatol [Internet]. 2015;11(4):223–33. https://doi.org/10.1038/nrrheum.2015.26.

    Article  Google Scholar 

  3. Hunt KJ, Hurwit D, Robell K, Gatewood C, Botser IB, Matheson G. Incidence and epidemiology of foot and ankle injuries in elite collegiate athletes. Am J Sports Med [Internet]. 2017;45(2):426–33. https://doi.org/10.1177/0363546516666815.

    Article  Google Scholar 

  4. Raikin SM, Garras DN, Krapchev PV. Achilles tendon injuries in a United States population. Foot Ankle Int [Internet]. 2013;34(4):475–80. https://doi.org/10.1177/1071100713477621.

    Article  Google Scholar 

  5. Lievers WB, Adamic PF. Incidence and severity of foot and ankle injuries in Men’s collegiate American football. Orthop J Sports Med. 2015;3(5):1–8.

    Article  Google Scholar 

  6. Durgam S, Stewart M. Cellular and molecular factors influencing tendon repair. Tissue Eng Part B Rev [Internet]. 2017;23(4):307–17. https://doi.org/10.1089/ten.teb.2016.0445.

    Article  Google Scholar 

  7. Wang A, Mccann P, Colliver J, Koh E, Ackland T, Joss B, et al. Do postoperative platelet-rich plasma injections accelerate early tendon healing and functional recovery after arthroscopic supraspinatus repair? A randomized controlled trial. Am J Sports Med. 2015;43(6):1430–7.

    Article  Google Scholar 

  8. De Almeida AM, Demange MK, Sobrado MF, Rodrigues MB, Pedrinelli A, Hernandez AJ. Patellar tendon healing with platelet-rich plasma: a prospective randomized controlled trial. Am J Sports Med. 2012;40(6):1282–8.

    Article  Google Scholar 

  9. Docheva D, Müller SA, Majewski M, Evans CH. Biologics for tendon repair [Internet]. Vol. 84, Advanced Drug Delivery Reviews. Elsevier; 2015 [cited 2018 Apr 23]. p. 222–39. https://www.sciencedirect.com/science/article/pii/S0169409X14002786

  10. Halper J. Progress in Heritable Soft Connective Tissue Diseases [Internet]. Vol. 802. 2014. http://link.springer.com/10.1007/978-94-007-7893-1

  11. Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg Ser A. 2005;87(1):187–202.

    Google Scholar 

  12. Nixon AJ, Watts AE, Schnabel LV. Cell- and gene-based approaches to tendon regeneration. J Shoulder Elb Surg [Internet]. 2012;21(2):278–94. https://doi.org/10.1016/j.jse.2011.11.015.

    Article  Google Scholar 

  13. James R, Kesturu G, Balian G, Chhabra AB. Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. J Hand Surg Am. 2008;33(1):102–12.

    Article  Google Scholar 

  14. Müller SA, Todorov A, Heisterbach PE, Martin I, Majewski M. Tendon healing: an overview of physiology, biology, and pathology of tendon healing and systematic review of state of the art in tendon bioengineering. Knee Surg Sport Traumatol Arthrosc. 2015;23(7):2097–105.

    Article  Google Scholar 

  15. Youngmisuk O. Lonzo Ball had PRP shot, stayed off court for 1 month. ESPN. 2018;NBA (June 11).

    Google Scholar 

  16. Pas HIMFL, Moen MH, Haisma HJ, Winters M. No evidence for the use of stem cell therapy for tendon disorders: a systematic review. Br J Sports Med [Internet]. 2017;51(13):996–1002. https://doi.org/10.1136/bjsports-2016-096794.

    Article  Google Scholar 

  17. Xu K, Al-ani MK, Sun Y, Xu W, Pan L, Song Y, et al. Platelet-rich plasma activates tendon-derived stem cells to promote regeneration of Achilles tendon rupture in rats. J Tissue Eng Regen Med. 2017;11(4):1173–84.

    Article  CAS  Google Scholar 

  18. Seijas R, Ares O, Catala J, Alvarez-Diaz P, Cusco X, Cugat R. Magnetic resonance imaging evaluation of patellar tendon graft remodelling after anterior cruciate ligament reconstruction with or without platelet-rich plasma. J Orthop Surg [Internet]. 2013;21(1):10–4. https://doi.org/10.1177/230949901302100105.

    Article  Google Scholar 

  19. Gumina S, Campagna V, Ferrazza G, Giannicola G, Fratalocchi F, Milani A, et al. Use of platelet-leukocyte membrane in arthroscopic repair of large rotator cuff tears. J Bone Joint Surg Am [Internet]. 2012;94(15):1345–52. http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00004623-201208010-00001

    Article  Google Scholar 

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

    Article  Google Scholar 

  21. Chan BP, Fu SC, Qin L, Rolf C, Chan KM. Supplementation-time dependence of growth factors in promoting tendon healing. Clin Orthop Relat Res. 2006;448:240–7.

    Article  CAS  Google Scholar 

  22. Yoshikawa Y, Abrahamsson SO. Dose-related cellular effects of platelet-derived growth factor-BB differ in various types of rabbit tendons in vitro. Acta Orthop Scand. 2001;72(3):287–92.

    Article  CAS  Google Scholar 

  23. Hildebrand K, Woo S. The effects of platelet-derived growth factor-BB on healing of the rabbit medial collateral ligament an in vivo study. Am J Sports Med [Internet]. 1998;26(4):549–54. http://ajs.sagepub.com/content/26/4/549.short

    Article  CAS  Google Scholar 

  24. Tokunaga T, Ide J, Arimura H, Nakamura T, Uehara Y, Sakamoto H, et al. Local application of gelatin hydrogel sheets impregnated with platelet-derived growth factor BB promotes tendon-to-bone healing after rotator cuff repair in rats. Arthroscopy [Internet]. 2015;31(8):1482–91. https://doi.org/10.1016/j.arthro.2015.03.008.

    Article  Google Scholar 

  25. Nevins M, Giannobile WV, McGuire MK, Kao RT, Mellonig JT, Hinrichs JE, et al. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. J Periodontol [Internet]. 2005;76(12):2205–15. https://doi.org/10.1902/jop.2005.76.12.2205.

    Article  CAS  Google Scholar 

  26. Anaguchi Y, Yasuda K, Majima T, Tohyama H, Minami A, Hayashi K. The effect of transforming growth factor-beta on mechanical properties of the fibrous tissue regenerated in the patellar tendon after resecting the central portion. Clin Biomech. 2005;20(9):959–65.

    Article  Google Scholar 

  27. Lu L, Saulis AS, Liu WR, Roy NK, Chao JD, Ledbetter S, et al. The temporal effects of anti-TGF-β1, 2, and 3 monoclonal antibody on wound healing and hypertrophic scar formation. J Am Coll Surg. 2005;201(3):391–7.

    Article  Google Scholar 

  28. Loiselle AE, Yukata K, Geary MB, Kondabolu S, Shi S, Jonason JH, et al. Development of antisense oligonucleotide (ASO) technology against Tgf-β signaling to prevent scarring during flexor tendon repair. J Orthop Res. 2015;33(6):859–66.

    Article  CAS  Google Scholar 

  29. Chang J, Thunder R, Most D, Longaker MT, Lineaweaver WC. Studies in flexor tendon wound healing: neutralizing antibody to TGF-B1 increases postoperative range of motion [Internet]. Vol. 105, Plastic and reconstructive surgery. 2000. p. 148–55. http://pdfs.journals.lww.com/plasreconsurg/2000/01000/Studies_in_Flexor_Tendon_Wound_Healing_.00025.pdf

  30. Dahlgren LA, Van Der Meulen MCH, Bertram JEA, Starrak GS, Nixon AJ. Insulin-like growth factor-I improves cellular and molecular aspects of healing in a collagenase-induced model of flexor tendinitis. J Orthop Res. 2002;20(5):910–9.

    Article  CAS  Google Scholar 

  31. Kobayashi D, Kurosaka M, Yoshiya S, Mizuno K. Effect of basic fibroblast growth factor on the healing of defects in the canine anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc. 1997;5:189–94.

    Article  CAS  Google Scholar 

  32. Zhang F, Liu H, Stile F, Lei M-P, Pang Y, Oswald TM, et al. Effect of vascular endothelial growth factor on rat achilles tendon healing. Plast Reconstr Surg [Internet]. 2003;112(6):1613–9. http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00006534-200311000-00017

    Article  Google Scholar 

  33. Evans CH. Advances in regenerative orthopedics. Mayo Clin Proc [Internet]. 2013;88(11):1323–9. https://doi.org/10.1016/j.mayocp.2013.04.027.

    Article  Google Scholar 

  34. Gross G, Hoffmann A. Therapeutic strategies for tendon healing based on novel biomaterials, factors and cells. Pathobiology. 2013;80(4):203–10.

    Article  CAS  Google Scholar 

  35. Longo UG, Lamberti A, Petrillo S, Maffulli N, Denaro V. Scaffolds in tendon tissue engineering. Stem Cells Int. 2012;2012:517165.

    PubMed  Google Scholar 

  36. Wang S, Wang Y, Song L, Chen J, Ma Y, Chen Y, et al. Decellularized tendon as a prospective scaffold for tendon repair. Mater Sci Eng C [Internet]. 2017;77:1290–301. https://doi.org/10.1016/j.msec.2017.03.279.

    Article  CAS  Google Scholar 

  37. Wang W, Deng D, Wang B, Zhou G, Zhang W, Cao Y, et al. *Comparison of autologous, allogeneic, and cell-free scaffold approaches for engineered tendon repair in a rabbit model-A pilot study. Tissue Eng Part A [Internet]. 2017;23(15–16):750–61. https://doi.org/10.1089/ten.tea.2016.0447.

    Article  CAS  Google Scholar 

  38. Huang D, Balian G, Chhabra AB. Tendon tissue engineering and gene transfer: the future of surgical treatment. J Hand Surg Am. 2006;31(5):693–704.

    Article  CAS  Google Scholar 

  39. Uysal AC, Mizuno H. Tendon regeneration and repair with adipose derived stem cells. Curr Stem Cell Res Ther. 2010;5(2):161–7.

    Article  CAS  Google Scholar 

  40. Chamberlain CS, Saether EE, Aktas E, Vanderby R. Mesenchymal stem cell therapy on tendon/ligament healing immunosuppressive effects of mesenchymal stem cells on. Journal of Cytokine Biology. 2017;2(1):2–7.

    Google Scholar 

  41. Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, et al. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop. 2014;38(9):1811–8.

    Article  Google Scholar 

  42. Kraus TM, Imhoff FB, Wexel G, Wolf A, Hirsch D, Lenz L, et al. Stem cells and basic fibroblast growth factor failed to improve tendon healing. J Bone Joint Surg Am [Internet]. 2014;96(9):761–9. http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00004623-201405070-00012

    Article  CAS  Google Scholar 

  43. Li Y, Ramcharan M, Zhou Z, Leong DJ, Akinbiyi T, Majeska RJ, et al. The role of scleraxis in fate determination of mesenchymal stem cells for tenocyte differentiation. Sci Rep [Internet]. 2015;5(March):1–12. https://doi.org/10.1038/srep13149.

    Article  CAS  Google Scholar 

  44. Hoffmann A, Pelled G, Turgeman G, Eberle P, Zilberman Y, Shinar H, et al. Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells. J Clin Invest. 2006;116(4):940–52.

    Article  CAS  Google Scholar 

  45. Hsieh CF, Alberton P, Loffredo-Verde E, Volkmer E, Pietschmann M, Müller P, et al. Scaffold-free Scleraxis-programmed tendon progenitors aid in significantly enhanced repair of full-size Achilles tendon rupture. Nanomedicine. 2016;11(9):1153–67.

    Article  CAS  Google Scholar 

  46. Dines JS, Grande DA, Dines DM. Tissue engineering and rotator cuff tendon healing. J Shoulder Elb Surg. 2007;16(5 Suppl):204–7.

    Article  Google Scholar 

  47. Liu L, Hindieh J, Leong DJ, Sun HB. Advances of stem cell based-therapeutic approaches for tendon repair. J Orthop Transl [Internet]. 2017;9:69–75. https://doi.org/10.1016/j.jot.2017.03.007.

    Article  CAS  Google Scholar 

  48. Behfar M, Sarrafzadeh-Rezaei F, Hobbenaghi R, Delirezh N, Dalir-Naghadeh B. Enhanced mechanical properties of rabbit flexor tendons in response to intratendinous injection of adipose derived stromal vascular fraction. Curr Stem Cell Res Ther [Internet]. 2012;7(3):173–8. http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1574-888X&volume=7&issue=3&spage=173

    Article  CAS  Google Scholar 

  49. Gonçalves AI, Gershovich PM, Rodrigues MT, Reis RL, Gomes ME. Human adipose tissue-derived tenomodulin positive subpopulation of stem cells: a promising source of tendon progenitor cells. J Tissue Eng Regen Med. 2018;12(3):762–74.

    Article  Google Scholar 

  50. Dale TP, Mazher S, Webb WR, Zhou J, Maffulli N, Chen G-Q, et al. Tenogenic differentiation of human embryonic stem cells. Tissue Eng Part A. 2018;24:361–8. https://doi.org/10.1089/ten.tea.2017.0017.

    Article  CAS  PubMed  Google Scholar 

  51. Xu W, Wang Y, Liu E, Sun Y, Luo Z, Xu Z, et al. Human iPSC-derived neural crest stem cells promote tendon repair in a rat patellar tendon window defect model. Tissue Eng Part A. 2013;19(21–22):2439–51. https://doi.org/10.1089/ten.tea.2012.0453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Fukui N, Katsuragawa Y, Sakai H, et al. Effect of local application of basic fibroblast growth factor on ligament healing in rabbits. Rev Rhum Engl Ed 1998;65 (6):406–14.

    Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedics, Foot and Ankle Surgery, University of California-Davis, Davis Medical Center, Sacramento, CA, USA

    Kimberly Allen, Enrique Feria-Arias, Christopher Kreulen & Eric Giza

Authors
  1. Kimberly Allen
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  2. Enrique Feria-Arias
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  3. Christopher Kreulen
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  4. Eric Giza
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Corresponding author

Correspondence to Eric Giza .

Editor information

Editors and Affiliations

  1. Centre of Sports Traumatology Koelliker Hospital, Torino, Italy

    Gian Luigi Canata

  2. Department of Orthopaedic Surgery, Aspetar Hospital, Doha, Qatar

    Pieter d'Hooghe

  3. Department of Orthopedics, University of Colorado Hospital, Aurora, CO, USA

    Kenneth J. Hunt

  4. Department of Orthopedic Surgery, University of Amsterdam Academic Medical Center, Amsterdam Zuidoost, Noord-Holland, The Netherlands

    Gino M.M.J. Kerkhoffs

  5. Orthopaedics and Traumatology Unit, University Campus Bio medico, Rome, Italy

    Umile Giuseppe Longo

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Allen, K., Feria-Arias, E., Kreulen, C., Giza, E. (2019). Biologics in the Foot and Ankle. In: Canata, G., d'Hooghe, P., Hunt, K., Kerkhoffs, G., Longo, U. (eds) Sports Injuries of the Foot and Ankle. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-58704-1_27

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  • DOI: https://doi.org/10.1007/978-3-662-58704-1_27

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