Hyaluronic Acid

  • Hélder PereiraEmail author
  • Duarte Andre Sousa
  • António Cunha
  • Renato Andrade
  • J. Espregueira-Mendes
  • J. Miguel Oliveira
  • Rui L. Reis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1059)


In recent times, the field of tissue engineering and regenerative medicine (TERM) has considerably increased the extent of therapeutic strategies for clinical application in orthopedics. However, TERM approaches have its rules and requirements, in the respect of the biologic response of each tissue and bioactive agents which need to be considered, respected, and subject of ongoing studies. Different medical devices/products have been prematurely available on the market and used in clinics with limited success. However, other therapeutics, when used in a serious and evidence-based approach, have achieved considerable success, considering the respect for solid expectations from doctors and patients (when properly informed).

Orthobiologics has appeared as a recent technological trend in orthopedics. This includes the improvement or regeneration of different musculoskeletal tissues by means of using biomaterials (e.g., hyaluronic acid), stem cells, and growth factors (e.g., platelet-rich plasma). The potential symbiotic relationship between biologic therapies and surgery makes these strategies suitable to be used in one single intervention.

However, herein, the recent clinical studies using hyaluronic acid (HA) in the treatment of orthopedic conditions will mainly be overviewed (e.g., osteochondral lesions, tendinopathies). The possibilities to combine different orthobiologic agents as TERM clinical strategies for treatment of orthopedic problems will also be briefly discussed.


Osteochondral lesions Tendinopathies Orthobiologics Hyaluronic acid Stem cells Platelet-rich plasma Growth factors Tissue engineering and regenerative medicine 


  1. 1.
    Xing D, Wang B, Liu Q, Ke Y, Xu Y, Li Z, Lin J (2016) Intra-articular hyaluronic acid in treating knee osteoarthritis: a PRISMA-compliant systematic review of overlapping meta-analysis. Sci Rep 6:32790. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Puig-Junoy J, Ruiz Zamora A (2015) Socio-economic costs of osteoarthritis: a systematic review of cost-of-illness studies. Semin Arthritis Rheum 44(5):531–541. CrossRefPubMedGoogle Scholar
  3. 3.
    Hunter DJ (2009) Risk stratification for knee osteoarthritis progression: a narrative review. Osteoarthr Cartil/OARS Osteoarthr Res Soc 17(11):1402–1407. CrossRefGoogle Scholar
  4. 4.
    van Dijk CN, Reilingh ML, Zengerink M, van Bergen CJ (2010) Osteochondral defects in the ankle: why painful? Knee Surg Sports Traumatol Arthrosc Off J ESSKA 18(5):570–580. CrossRefGoogle Scholar
  5. 5.
    Temenoff JS, Mikos AG (2000) Review: tissue engineering for regeneration of articular cartilage. Biomaterials 21(5):431–440CrossRefGoogle Scholar
  6. 6.
    Hunziker EB (2000) Articular cartilage repair: problems and perspectives. Biorheology 37(1-2):163–164PubMedGoogle Scholar
  7. 7.
    Pacifici M, Koyama E, Iwamoto M, Gentili C (2000) Development of articular cartilage: what do we know about it and how may it occur? Connect Tissue Res 41(3):175–184CrossRefPubMedGoogle Scholar
  8. 8.
    Kuettner KE, Cole AA (2005) Cartilage degeneration in different human joints. Osteoarthr Cartil/OARS Osteoarthr Res Soc 13(2):93–103. CrossRefGoogle Scholar
  9. 9.
    Gelber AC, Hochberg MC, Mead LA, Wang NY, Wigley FM, Klag MJ (2000) Joint injury in young adults and risk for subsequent knee and hip osteoarthritis. Ann Intern Med 133(5):321–328CrossRefPubMedGoogle Scholar
  10. 10.
    de Vos RJ, van PLJ V, Moen MH, Weir A, Tol JL, Maffulli N (2010) Autologous growth factor injections in chronic tendinopathy: a systematic review. Br Med Bull 95(1):63–77. CrossRefPubMedGoogle Scholar
  11. 11.
    van Sterkenburg MN, van Dijk CN (2011) Injection treatment for chronic midportion Achilles tendinopathy: do we need that many alternatives? Knee Surg Sports Traumatol Arthrosc Off J ESSKA 19(4):513–515. CrossRefGoogle Scholar
  12. 12.
    Snedeker JG, Foolen J (2017) Tendon injury and repair - a perspective on the basic mechanisms of tendon disease and future clinical therapy. Acta Biomater 63:18–36. CrossRefPubMedGoogle Scholar
  13. 13.
    Weinraub GM (2005) Orthobiologics: a survey of materials and techniques. Clin Podiatr Med Surg 22(4):509–519., v. CrossRefPubMedGoogle Scholar
  14. 14.
    Correia SI, Pereira H, Silva-Correia J, Van Dijk CN, Espregueira-Mendes J, Oliveira JM, Reis RL (2014) Current concepts: tissue engineering and regenerative medicine applications in the ankle joint. J R Soc Interface R Soc 11(92):20130784. CrossRefGoogle Scholar
  15. 15.
    de Mos M, van der Windt AE, Jahr H, van Schie HT, Weinans H, Verhaar JA, van Osch GJ (2008) Can platelet-rich plasma enhance tendon repair? A cell culture study. Am J Sports Med 36(6):1171–1178. CrossRefPubMedGoogle Scholar
  16. 16.
    DeChellis DM, Cortazzo MH (2011) Regenerative medicine in the field of pain medicine: prolotherapy, platelet-rich plasma therapy, and stem cell therapy—theory and evidence. Tech Reg Anesth Pain Manag 15:74–80CrossRefGoogle Scholar
  17. 17.
    Evans CH (2013) Platelet-rich plasma a la carte: commentary on an article by Satoshi Terada, MD, et al.: “use of an antifibrotic agent improves the effect of platelet-rich plasma on muscle healing after injury”. J Bone Joint Surg Am 95(11):e801–e802. CrossRefPubMedGoogle Scholar
  18. 18.
    Luyten FP, Vanlauwe J (2012) Tissue engineering approaches for osteoarthritis. Bone 51(2):289–296. CrossRefPubMedGoogle Scholar
  19. 19.
    Martel-Pelletier J, Wildi LM, Pelletier JP (2012) Future therapeutics for osteoarthritis. Bone 51(2):297–311. CrossRefPubMedGoogle Scholar
  20. 20.
    Qi Y, Feng G, Yan W (2012) Mesenchymal stem cell-based treatment for cartilage defects in osteoarthritis. Mol Biol Rep 39(5):5683–5689. CrossRefPubMedGoogle Scholar
  21. 21.
    Nordsletten L (2006) Recent developments in the use of bone morphogenetic protein in orthopaedic trauma surgery. Curr Med Res Opin 22(s1):S13–S17. CrossRefPubMedGoogle Scholar
  22. 22.
    Myers KR (2013) Trends in biological joint resurfacing. Bone Joint Res 2(9):193–199. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Pereira H, Ripoll L, Oliveira JM, Reis RL, Espregueira-Mendes J, van Dijk C (2016) A Engenharia de tecidos nas lesões do Desporto. Traumatologia Desportiva. LIDEL, LisboaGoogle Scholar
  24. 24.
    Di Giacomo G, De Gasperis N (2015) The role of hyaluronic acid in patients affected by glenohumeral osteoarthritis. J Biol Regul Homeost Agents 29(4):945–951PubMedGoogle Scholar
  25. 25.
    Flores C, Balius R, Alvarez G, Buil MA, Varela L, Cano C, Casariego J (2017) Efficacy and tolerability of Peritendinous hyaluronic acid in patients with supraspinatus Tendinopathy: a multicenter, randomized, controlled trial. Sports Med Open 3(1):22. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Gigante A, Callegari L (2011) The role of intra-articular hyaluronan (Sinovial) in the treatment of osteoarthritis. Rheumatol Int 31(4):427–444. CrossRefPubMedGoogle Scholar
  27. 27.
    Van Den Bekerom MP, Mylle G, Rys B, Mulier M (2006) Viscosupplementation in symptomatic severe hip osteoarthritis: a review of the literature and report on 60 patients. Acta Orthop Belg 72(5):560–568Google Scholar
  28. 28.
    Zengerink M, Struijs PA, Tol JL, van Dijk CN (2010) Treatment of osteochondral lesions of the talus: a systematic review. Knee Surg Sports Traumatol Arthrosc Off J ESSKA 18(2):238–246. CrossRefGoogle Scholar
  29. 29.
    Necas J, Bartosikova L, Brauner P, Kolar J (2008) Hyaluronic acid (hyaluronan): a review. Veterinarni Medicina 53(8):397–411CrossRefGoogle Scholar
  30. 30.
    Collins MN, Birkinshaw C (2013) Hyaluronic acid based scaffolds for tissue engineering—a review. Carbohydr Polym 92(2):1262–1279. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Witteveen AG, Hofstad CJ, Kerkhoffs GM (2015) Hyaluronic acid and other conservative treatment options for osteoarthritis of the ankle. Cochrane Database Syst Rev 10:CD010643. CrossRefGoogle Scholar
  32. 32.
    Bonnet F, Dunham DG, Hardingham TE (1979) Structure and interactions of cartilage proteoglycan binding region and link protein. Biochem J 228:77–85CrossRefGoogle Scholar
  33. 33.
    McArthur BA, Dy CJ, Fabricant PD, Valle AG (2012) Long term safety, efficacy, and patient acceptability of hyaluronic acid injection in patients with painful osteoarthritis of the knee. Patient Prefer Adherence 6:905–910. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85(8):699–715. CrossRefPubMedGoogle Scholar
  35. 35.
    Stern R, Kogan G, Jedrzejas MJ, Šoltés L (2007) The many ways to cleave hyaluronan. Biotechnol Adv 25(6):537–557. CrossRefPubMedGoogle Scholar
  36. 36.
    Toole BP (2001) Hyaluronan in morphogenesis. Semin Cell Dev Biol 12(2):79–87. CrossRefPubMedGoogle Scholar
  37. 37.
    Strauss EJ, Hart JA, Miller MD, Altman RD, Rosen JE (2009) Hyaluronic acid Viscosupplementation and osteoarthritis: current uses and future directions. Am J Sports Med 37(8):1636–1644. CrossRefPubMedGoogle Scholar
  38. 38.
    Toole BP (2004) Hyaluronan: From extracellular glue to pericellular cue. Nat Rev Cancer 4(7):528–539. CrossRefPubMedGoogle Scholar
  39. 39.
    Bollyky P, Bogdani M, Bollyky J, Hull R, Wight T (2012) The role of Hyaluronan and the extracellular matrix in islet inflammation and immune regulation. Curr Diab Rep 12(5):471–480. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Preston M, Sherman L (2011) Neural stem cell niches: critical roles for the hyaluronan-based matrix in neural stem cell proliferation and differentiation. Front Biosci 3:1165–1179CrossRefGoogle Scholar
  41. 41.
    Balazs EA, Denlinger JL (1993) Viscosupplementation: a new concept in the treatment of osteoarthritis. J Rheumatol Suppl 39:3–9PubMedGoogle Scholar
  42. 42.
    Moreland LW (2003) Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action. Arthritis Res Ther 5(2):54–67CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Lynen N, De Vroey T, Spiegel I, Van Ongeval F, Hendrickx NJ, Stassijns G (2017) Comparison of Peritendinous Hyaluronan injections versus extracorporeal shock wave therapy in the treatment of painful Achilles’ Tendinopathy: a randomized clinical efficacy and safety study. Arch Phys Med Rehabil 98(1):64–71. CrossRefPubMedGoogle Scholar
  44. 44.
    Araujo JP, Silva L, Andrade R, Pacos M, Moreira H, Migueis N, Pereira R, Sarmento A, Pereira H, Loureiro N, Espregueira-Mendes J (2016) Pain reduction and improvement of function following ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid in hip osteoarthritis. J Biol Regul Homeost Agents 30(4 Suppl 1):51–62PubMedGoogle Scholar
  45. 45.
    Bannuru RR, Natov NS, Dasi UR, Schmid CH, McAlindon TE (2011) Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis. Osteoarthr Cartil/OARS Osteoarthr Res Soc 19(6):611–619. CrossRefGoogle Scholar
  46. 46.
    Wang CT, Lin J, Chang CJ, Lin YT, Hou SM (2004) Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomized controlled trials. J Bone Joint Surg Am 86-a(3):538–545CrossRefPubMedGoogle Scholar
  47. 47.
    Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G (2006) Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev (2):Cd005321.
  48. 48.
    Karatosun V, Unver B, Ozden A, Ozay Z, Gunal I (2008) Intra-articular hyaluronic acid compared to exercise therapy in osteoarthritis of the ankle. A prospective randomized trial with long-term follow-up. Clin Exp Rheumatol 26(2):288–294PubMedGoogle Scholar
  49. 49.
    Migliore A, Bizzi E, Massafra U, Vacca F, Alimonti A, Iannessi F, Tormenta S (2009) Viscosupplementation: a suitable option for hip osteoarthritis in young adults. Eur Rev Med Pharmacol Sci 13(6):465–472PubMedGoogle Scholar
  50. 50.
    Monfort J, Rotes-Sala D, Segales N, Montanes FJ, Orellana C, Llorente-Onaindia J, Mojal S, Padro I, Benito P (2015) Comparative efficacy of intra-articular hyaluronic acid and corticoid injections in osteoarthritis of the first carpometacarpal joint: results of a 6-month single-masked randomized study. Joint Bone Spine 82(2):116–121. CrossRefPubMedGoogle Scholar
  51. 51.
    Porcellini G, Merolla G, Giordan N, Paladini P, Burini A, Cesari E, Castagna A (2015) Intra-articular glenohumeral injections of HYADD(R)4-G for the treatment of painful shoulder osteoarthritis: a prospective multicenter, open-label trial. Joints 3(3):116–121. CrossRefPubMedGoogle Scholar
  52. 52.
    Legre-Boyer V (2015) Viscosupplementation: techniques, indications, results. Orthop Trauma Surg Res OTSR 101(1s):S101–s108. CrossRefGoogle Scholar
  53. 53.
    Braithwaite GJ, Daley MJ, Toledo-Velasquez D (2016) Rheological and molecular weight comparisons of approved hyaluronic acid products - preliminary standards for establishing class III medical device equivalence. J Biomater Sci Polym Ed 27(3):235–246. CrossRefPubMedGoogle Scholar
  54. 54.
    Ayhan E, Kesmezacar H, Akgun I (2014) Intraarticular injections (corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis. World J Orthop 5(3):351–361. CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Buda R, Vannini F, Cavallo M, Baldassarri M, Luciani D, Mazzotti A, Pungetti C, Olivieri A, Giannini S (2013) One-step arthroscopic technique for the treatment of osteochondral lesions of the knee with bone-marrow-derived cells: three years results. Musculoskelet Surg 97(2):145–151. CrossRefPubMedGoogle Scholar
  56. 56.
    Doral MN, Bilge O, Batmaz G, Donmez G, Turhan E, Demirel M, Atay OA, Uzumcugil A, Atesok K, Kaya D (2012) Treatment of osteochondral lesions of the talus with microfracture technique and postoperative hyaluronan injection. Knee Surg Sports Traumatol Arthrosc Off J ESSKA 20(7):1398–1403. CrossRefGoogle Scholar
  57. 57.
    Giannini S, Buda R, Battaglia M, Cavallo M, Ruffilli A, Ramponi L, Pagliazzi G, Vannini F (2013) One-step repair in talar osteochondral lesions: 4-year clinical results and t2-mapping capability in outcome prediction. Am J Sports Med 41(3):511–518. CrossRefPubMedGoogle Scholar
  58. 58.
    Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, Fornasari PM, Giannini S, Marcacci M (2011) Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy J Arthrosc Relat Surg Off Publ Arthrosc Assoc North Am Int Arthrosc Assoc 27(11):1490–1501. CrossRefGoogle Scholar
  59. 59.
    Mason LW, Wilson-Jones N, Williams P (2014) The use of a cell-free chondroinductive implant in a child with massive cartilage loss of the talus after an open fracture dislocation of the ankle: a case report. J Pediatr Orthop 34(8):e58–e62. CrossRefPubMedGoogle Scholar
  60. 60.
    Wong KL, Lee KB, Tai BC, Law P, Lee EH, Hui JH (2013) Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up. Arthroscopy J Arthrosc Relat Surg Off Publ Arthrosc Assoc North Am Int Arthrosc Assoc 29(12):2020–2028. CrossRefGoogle Scholar
  61. 61.
    Colen S, Geervliet P, Haverkamp D, Van Den Bekerom MP (2014) Intra-articular infiltration therapy for patients with glenohumeral osteoarthritis: a systematic review of the literature. Int J Shoulder Surg 8(4):114–121. CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Trellu S, Dadoun S, Berenbaum F, Fautrel B, Gossec L (2015) Intra-articular injections in thumb osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Joint Bone Spine 82(5):315–319. CrossRefPubMedGoogle Scholar
  63. 63.
    Abat F, Alfredson H, Cucchiarini M, Madry H, Marmotti A, Mouton C, Oliveira JM, Pereira H, Peretti GM, Romero-Rodriguez D, Spang C, Stephen J, van Bergen CJA, de Girolamo L (2017) Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part I: biology, biomechanics, anatomy and an exercise-based approach. J Exp Orthop 4(1):18. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Frizziero A, Vittadini F, Barazzuol M, Gasparre G, Finotti P, Meneghini A, Maffulli N, Masiero S (2017) Extracorporeal shockwaves therapy versus hyaluronic acid injection for the treatment of painful non-calcific rotator cuff tendinopathies: preliminary results. J Sports Med Phys Fitness 57(9):1162–1168. CrossRefPubMedGoogle Scholar
  65. 65.
    Kumai T, Muneta T, Tsuchiya A, Shiraishi M, Ishizaki Y, Sugimoto K, Samoto N, Isomoto S, Tanaka Y, Takakura Y (2014) The short-term effect after a single injection of high-molecular-weight hyaluronic acid in patients with enthesopathies (lateral epicondylitis, patellar tendinopathy, insertional Achilles tendinopathy, and plantar fasciitis): a preliminary study. J Orthop Sci 19(4):603–611. CrossRefPubMedGoogle Scholar
  66. 66.
    Wu PT, Jou IM, Kuo LC, Su FC (2016) Intratendinous injection of hyaluronate induces acute inflammation: a possible detrimental effect. PLoS One 11(5):e0155424. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Antunes JC, Oliveira JM, Reis RL, Soria JM, Gomez-Ribelles JL, Mano JF (2010) Novel poly(L-lactic acid)/hyaluronic acid macroporous hybrid scaffolds: characterization and assessment of cytotoxicity. J Biomed Mater Res A 94(3):856–869. CrossRefPubMedGoogle Scholar
  68. 68.
    Forriol F, Longo UG, Duart J, Ripalda P, Vaquero J, Loppini M, Romeo G, Campi S, Khan WS, Muda AO, Denaro V (2015) VEGF, BMP-7, Matrigel(TM), hyaluronic acid, in vitro cultured chondrocytes and trephination for healing of the avascular portion of the meniscus. An experimental study in sheep. Curr Stem Cell Res Ther 10(1):69–76CrossRefPubMedGoogle Scholar
  69. 69.
    Kon E, Filardo G, Robinson D, Eisman JA, Levy A, Zaslav K, Shani J, Altschuler N (2013) Osteochondral regeneration using a novel aragonite-hyaluronate bi-phasic scaffold in a goat model. Knee Surg Sports Traumatol Arthrosc. [Epub ahead of print]:1–13.
  70. 70.
    Anitua E, Sanchez M, De la Fuente M, Zalduendo MM, Orive G (2012) Plasma rich in growth factors (PRGF-Endoret) stimulates tendon and synovial fibroblasts migration and improves the biological properties of hyaluronic acid. Knee Surg Sports Traumatol Arthrosc Off J ESSKA 20(9):1657–1665. CrossRefGoogle Scholar
  71. 71.
    Chen WH, Lo WC, Hsu WC, Wei HJ, Liu HY, Lee CH, Tina Chen SY, Shieh YH, Williams DF, Deng WP (2014) Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy. Biomaterials 35(36):9599–9607. CrossRefPubMedGoogle Scholar
  72. 72.
    Srinivasan PP, McCoy SY, Jha AK, Yang W, Jia X, Farach-Carson MC, Kirn-Safran CB (2012) Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis. Biomed Mater 7(2):024109. CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Sanchez M, Azofra J, Anitua E, Andia I, Padilla S, Santisteban J, Mujika I (2003) Plasma rich in growth factors to treat an articular cartilage avulsion: a case report. Med Sci Sports Exerc 35(10):1648–1652. CrossRefPubMedGoogle Scholar
  74. 74.
    Tsaryk R, Gloria A, Russo T, Anspach L, De Santis R, Ghanaati S, Unger RE, Ambrosio L, Kirkpatrick CJ (2015) Collagen-low molecular weight hyaluronic acid semi-interpenetrating network loaded with gelatin microspheres for cell and growth factor delivery for nucleus pulposus regeneration. Acta Biomater 20:10–21. CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Hélder Pereira
    • 1
    • 2
    • 3
    • 4
    • 5
    Email author
  • Duarte Andre Sousa
    • 3
  • António Cunha
    • 5
  • Renato Andrade
    • 6
  • J. Espregueira-Mendes
    • 1
    • 2
    • 6
    • 7
    • 8
  • J. Miguel Oliveira
    • 1
    • 2
    • 4
    • 9
  • Rui L. Reis
    • 1
    • 2
    • 9
  1. 1.3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineBarco, GuimarãesPortugal
  2. 2.ICVS/3B’s – PT Government Associated LaboratoryBragaPortugal
  3. 3.Orthopedic Department of Póvoa de Varzim – Vila do Conde Hospital CentrePóvoa de VarzimPortugal
  4. 4.Ripoll y De Prado Sports Clinic: Murcia-Madrid FIFA Medical Centre of ExcellenceMurcia/MadridSpain
  5. 5.International Centre of Sports Traumatology of the AveTaipasPortugal
  6. 6.Clínica do Dragão, Espregueira-Mendes Sports Centre – FIFA Medical Centre of ExcellencePortoPortugal
  7. 7.Dom Henrique Research CentrePortoPortugal
  8. 8.Orthopedic Department, University of MinhoBragaPortugal
  9. 9.The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of MinhoGuimarãesPortugal

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