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The Future of Cartilage Repair

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Book cover Personalized Medicine in Healthcare Systems

Part of the book series: Europeanization and Globalization ((EAG,volume 5))

Abstract

Articular cartilage is a hyaline cartilage 2–4 mm thick. It is composed of 95% of dense extracellular matrix (ECM) and 5% of highly specialized cells called chondrocytes. Because of its avascular, aneural and alymphatic state, it has a limited repair potential. Articular cartilages’ main function is to provide smooth, lubricated surface for low friction articulation while minimizing the stress and strains on the matrix. Articular cartilage could be damaged by normal wear and tear or injury and it can cause severe pain, inflammation and some degree of disability. Its management consist of pharmacological (acetaminophen, NSAID, salicylate, selective COX-2 inhibitors or opioids) and non-pharmacological therapies. Non-pharmacological treatment includes physical therapy and decreasing the load in the joint by modifying patient’s habits. A new class of agents (symptomatic or disease modifying osteoarthritic drugs (S/DMOADs) including glucosamine and chondroitin sulfate is receiving wide publicity. At the same time, numerous published reports advising the use of hyaluronic acid injections: viscosupplementation in patients with symptomatic osteoarthritis. Operative treatment includes different surgical debridement and microfracture techniques, osteochondral autograft transfers, osteochondral allograft transplantation, etc. New techniques and concepts are being developed not only to treat damaged or diseased joint cartilage but also to find ways of achieving regeneration to normal cartilage that will give long-lasting improvements and allow patients to return to a fully active lifestyle. Nevertheless, as two stage procedures involving cell culture are expensive and cumbersome, there is an increasing push towards a single stage stem cell treatment. Currently, there are a number of new methods with cartilage repair aim, including autologous chondrocyte implantation (ACI), matrix-induced autologous chondrocyte implantation (MACI), intra-articular administration of autologous microfragmented fat tissue with Ad-MSCs, etc. In this chapter, we discuss some current treatments and the emerging strategies/techniques employed by researchers and physicians thriving to repair articular cartilage through biological means.

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Notes

  1. 1.

    Fanghänel et al. (2009).

  2. 2.

    Bhosale and Richardson (2008).

  3. 3.

    Primorac et al. (1994).

  4. 4.

    Primorac (1995).

  5. 5.

    Junqueira and Carneiro (2005).

  6. 6.

    Heijink et al. (2012).

  7. 7.

    Roman-Blas and Herrero-Beaumont (2014).

  8. 8.

    Peyron and Altman (1992).

  9. 9.

    Aigner and Schmitz (2011).

  10. 10.

    Burrage and Brinckerhoff (2007).

  11. 11.

    Fan et al. (2004).

  12. 12.

    Stannus et al. (2010).

  13. 13.

    van de Loo et al. (1995).

  14. 14.

    Abramson (2008).

  15. 15.

    Clancy (1999).

  16. 16.

    Dumond et al. (2003).

  17. 17.

    Loeser (2003).

  18. 18.

    Bonnet and Walsh (2005).

  19. 19.

    Sakkas and Platsoucas (2007).

  20. 20.

    Zhen et al. (2013).

  21. 21.

    Uygur et al. (2015).

  22. 22.

    Dieppe (2011).

  23. 23.

    Davies-Tuck et al. (2010).

  24. 24.

    Felson et al. (2003).

  25. 25.

    Hunter et al. (2006).

  26. 26.

    Wluka et al. (2009).

  27. 27.

    Neogi et al. (2009).

  28. 28.

    Brittberg and Winalski (2003).

  29. 29.

    Richmond et al. (2009).

  30. 30.

    Zhang et al. (2008a, b).

  31. 31.

    Zhang et al. (2004).

  32. 32.

    Towheed et al. (2006).

  33. 33.

    FDA (2005).

  34. 34.

    FDA (2004).

  35. 35.

    FDA (2005).

  36. 36.

    AAOS (2013).

  37. 37.

    Ronca et al. (1998).

  38. 38.

    Chan et al. (2006).

  39. 39.

    Tat et al. (2007).

  40. 40.

    Martel-Pelletier et al. (2010).

  41. 41.

    du Souich et al. (2009).

  42. 42.

    Leeb et al. (2000).

  43. 43.

    Richy et al. (2003).

  44. 44.

    Hochberg et al. (2008).

  45. 45.

    Wildi et al. (2011).

  46. 46.

    McCarty (1994).

  47. 47.

    Bassleer et al. (1998).

  48. 48.

    Reginster et al. (2001).

  49. 49.

    Clegg et al. (2006).

  50. 50.

    Lopes Junior and Inacio (2013).

  51. 51.

    Zeng et al. (2015).

  52. 52.

    Zhang et al. (2008a, b).

  53. 53.

    Lee et al. (2010).

  54. 54.

    Marmotti et al. (2015).

  55. 55.

    Borrione et al. (2010).

  56. 56.

    Ehrenfest et al. (2014).

  57. 57.

    Kon et al. (2010).

  58. 58.

    Filardo et al. (2012).

  59. 59.

    Bellamy et al. (2006).

  60. 60.

    Liu et al. (2013).

  61. 61.

    Arroll and Goodyear-Smith (2004).

  62. 62.

    Meenagh et al. (2004).

  63. 63.

    McDonough (1982).

  64. 64.

    Jüni et al. (2015).

  65. 65.

    Elmorsy et al. (2014).

  66. 66.

    Julovi et al. (2004).

  67. 67.

    Kobayashi et al. (2004).

  68. 68.

    Sasaki et al. (2004).

  69. 69.

    Lajeunesse et al. (2003).

  70. 70.

    Forsey et al. (2006).

  71. 71.

    Lu et al. (2013).

  72. 72.

    Hiraoka et al. (2009).

  73. 73.

    Dougados (2000).

  74. 74.

    Altman et al. (2015).

  75. 75.

    Tetteh et al. (2012).

  76. 76.

    Harnly (2007).

  77. 77.

    Kreuz et al. (2006a, b).

  78. 78.

    Steadman et al. (2001).

  79. 79.

    Steadman et al. (2010).

  80. 80.

    Miller et al. (2004).

  81. 81.

    Steadman et al. (2003).

  82. 82.

    Hangody et al. (2008).

  83. 83.

    Camp et al. (2014).

  84. 84.

    Brittberg et al. (1994).

  85. 85.

    Bartlett et al. (2005).

  86. 86.

    Sohn et al. (2002).

  87. 87.

    Zaslav et al. (2009).

  88. 88.

    Schneider et al. (2011).

  89. 89.

    Wei et al. (2013).

  90. 90.

    Friedenstein et al. (1976).

  91. 91.

    Pittenger et al. (1999).

  92. 92.

    Murphy et al. (2003).

  93. 93.

    Grigolo et al. (2009).

  94. 94.

    Nejadnik et al. (2010).

  95. 95.

    Osiris Therapeutics Announces Positive One Year Data from Chondrogen Trial for Knee Repair (2007).

  96. 96.

    Vega et al. (2015).

  97. 97.

    Paschos and Sennett (2017).

  98. 98.

    Lin and Lue (2013).

  99. 99.

    Caplan (2008).

  100. 100.

    Caplan and Correa (2011).

  101. 101.

    Zuk et al. (2002).

  102. 102.

    Stolzing et al. (2008).

  103. 103.

    Tremolada et al. (2016).

  104. 104.

    Koh et al. (2015).

  105. 105.

    Hudetz et al. (2017).

  106. 106.

    Centeno et al. (2010).

  107. 107.

    Potter and Foo (2006).

  108. 108.

    Guermazi et al. (2015).

  109. 109.

    Link et al. (2017).

  110. 110.

    Bobic (2000).

  111. 111.

    Schreiner et al. (2017).

  112. 112.

    Marlovits et al. (2006).

  113. 113.

    Choi et al. (2008).

  114. 114.

    Gray et al. (2008).

  115. 115.

    Young et al. (2005).

  116. 116.

    Williams et al. (2004).

  117. 117.

    Burstein et al. (2001).

  118. 118.

    Trattnig et al. (2008).

  119. 119.

    Trattnig et al. (2007).

  120. 120.

    Kurkijärvi et al. (2007).

  121. 121.

    Hesper et al. (2014).

  122. 122.

    Dunn et al. (2004).

  123. 123.

    Koff et al. (2007).

  124. 124.

    Welsch et al. (2008a).

  125. 125.

    Welsch et al. (2008b).

  126. 126.

    Duvvuri et al. (2001).

  127. 127.

    Mlynarik et al. (1999).

  128. 128.

    Amano et al. (2017).

  129. 129.

    Holtzman et al. (2010).

  130. 130.

    Wang et al. (2009).

  131. 131.

    Krusche-Mandl et al. (2012).

  132. 132.

    Trattnig et al. (2010).

  133. 133.

    Zbýň et al. (2012).

  134. 134.

    Raya et al. (2013).

  135. 135.

    Raya (2015).

  136. 136.

    Binks et al. (2013).

  137. 137.

    Apprich et al. (2012).

  138. 138.

    Singh et al. (2012).

  139. 139.

    Koller et al. (2017).

References

  • Abramson SB (2008) Osteoarthritis and nitric oxide. Osteoarthr Cartil 16(Suppl 2):S15–S20. https://doi.org/10.1016/s1063-4584(08)60008-4

    Article  Google Scholar 

  • Aigner T, Schmitz N (2011) Pathogenesis and pathology of osteoarthritis. In: Hochberg M, Silman A, Smolen J, Weinblatt M, Weisman M (eds) Rheumatology, 5th edn. Mosby Elsevier, Philadelphia, pp 1741–1759

    Chapter  Google Scholar 

  • Altman R, Manjoo A, Fierlinger A, Niazi F, Nicholls M (2015) The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord 16:321

    Article  Google Scholar 

  • Amano K, Li AK, Pedoia V, Koff MF, Krych AJ, Link TM et al (2017) Effects of surgical factors on cartilage can be detected using quantitative magnetic resonance imaging after anterior cruciate ligament reconstruction. Am J Sports Med 45(5):1075–1084

    Article  Google Scholar 

  • American Academy of Orthopaedic Surgeons (2013) Treatment of osteoarthritis of the knee, 2nd edn. American Academy of Orthopaedic Surgeons, Rosemont

    Google Scholar 

  • Apprich S, Trattnig S, Welsch GH, Noebauer-Huhmann IM, Sokolwski M, Hirschfeld C et al (2012) Assessment of articular cartilage repair tissue after matrix-associated autologous chondrocyte transplantation or the microfracture technique in the ankle joint using diffusion-weighted imaging at 3 Tesla. Osteoarthr Cartil 20(7):703–711

    Article  Google Scholar 

  • Arroll B, Goodyear-Smith F (2004) Corticosteroid injections for osteoarthritis of the knee: meta-analysis. BMJ 328(7444):869

    Article  Google Scholar 

  • Bartlett W, Skinner JA, Gooding CR, Carrington RWJ, Flanagan AM, Briggs TWR, Bentley G (2005) Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective, randomised study. Bone Joint J 87(5):640–645

    Google Scholar 

  • Bassleer C, Rovati L, Franchimont P (1998) Stimulation of proteglycan production by glucosamine sulfate in chondrocite isolated from human osteoarthritic cartilage in vitro. Osteoarthr Cartil 6(6):427–434

    Article  Google Scholar 

  • Bellamy N, Campbell J, Welch V, Gee TL, Bourne R, Wells GA (2006) Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev (2): CD005321. https://doi.org/10.1002/14651858.CD005321.pub2

  • Bhosale AM, Richardson JB (2008) Articular cartilage: structure, injuries and review of management. Br Med Bull 87(1):77–95

    Article  Google Scholar 

  • Binks DA, Hodgson RJ, Ries ME, Foster RJ, Smye SW, McGonagle D, Radjenovic A (2013) Quantitative parametric MRI of articular cartilage: a review of progress and open challenges. Br J Radiol 86(1023):20120163

    Article  Google Scholar 

  • Bobic V (2000) ICRS articular cartilage imaging committee. ICRS MR imaging protocol for knee articular cartilage. International Cartilage Repair Society, Wetzikon, Switzerland, p 12

    Google Scholar 

  • Bonnet CS, Walsh DA (2005) Osteoarthritis, angiogenesis and inflammation. Rheumatology (Oxford) 44(1):7–16. https://doi.org/10.1093/rheumatology/keh344

    Article  Google Scholar 

  • Borrione P, Di Gianfrancesco A, Pereira MT, Pigozzi F (2010) Platelet-rich plasma in muscle healing. Am J Phys Med Rehabil 89(10):854–861

    Article  Google Scholar 

  • Brittberg M, Winalski CS (2003) Evaluation of cartilage injuries and repair. J Bone Joint Surg Am 85(suppl 2):58–69

    Article  Google Scholar 

  • Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331(14):889–895

    Article  Google Scholar 

  • Burrage PS, Brinckerhoff CE (2007) Molecular targets in osteoarthritis: metalloproteinases and their inhibitors. Curr Drug Targets 8(2):293–303

    Article  Google Scholar 

  • Burstein D, Velyvis J, Scott KT, Stock KW, Kim YJ, Jaramillo D et al (2001) Protocol issues for delayed Gd (DTPA) 2–-enhanced MRI (dGEMRIC) for clinical evaluation of articular cartilage. Magn Reson Med 45(1):36–41

    Article  Google Scholar 

  • Camp CL, Stuart MJ, Krych AJ (2014) Current concepts of articular cartilage restoration techniques in the knee. Sports Health 6(3):265–273

    Article  Google Scholar 

  • Caplan AI (2008) All MSCs are pericytes? Cell Stem Cell 3(3):229–230

    Article  Google Scholar 

  • Caplan AI, Correa D (2011) The MSC: an injury drugstore. Cell Stem Cell 9(1):11–15

    Article  Google Scholar 

  • Centeno CJ, Schultz JR, Cheever M, Robinson B, Freeman M, Marasco W (2010) Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther 5(1):81–93

    Article  Google Scholar 

  • Chan PS, Caron JP, Orth MW (2006) Short-term gene expression changes in cartilage explants stimulated with interleukin beta plus glucosamine and chondroitin sulfate. J Rheumatol 33:1329–1340

    Google Scholar 

  • Choi YS, Potter HG, Chun TJ (2008) MR imaging of cartilage repair in the knee and ankle. Radiographics 28(4):1043–1059

    Article  Google Scholar 

  • Clancy R (1999) Nitric oxide alters chondrocyte function by disrupting cytoskeletal signaling complexes. Osteoarthr Cartil 7(4):399–400. https://doi.org/10.1053/joca.1998.0223

    Article  Google Scholar 

  • Clegg DO, Reda DJ, Harris CL, Klein MA, O’Dell JR, Hooper MM et al (2006) Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 354(8):795–808

    Article  Google Scholar 

  • Davies-Tuck ML, Wluka AE, Forbes A, Wang Y, English DR, Giles GG et al (2010) Development of bone marrow lesions is associated with adverse effects on knee cartilage while resolution is associated with improvement-a potential target for prevention of knee osteoarthritis: a longitudinal study. Arthritis Res Ther 12(1):1

    Article  Google Scholar 

  • Dieppe P (2011) Developments in osteoarthritis. Rheumatology 50(2):245–247

    Article  Google Scholar 

  • Dougados M (2000) Sodium hyaluronate therapy in osteoarthritis: arguments for a potential beneficial structural effect. Semin Arthritis Rheum 30(2 Suppl 1):19–25

    Article  Google Scholar 

  • du Souich P, García AG, Vergés J, Montell E (2009) Immunomodulatory and anti-inflammatory effects of chondroitin sulphate. J Cell Mol Med 13(8a):1451–1463

    Article  Google Scholar 

  • Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P, Pottie P (2003) Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum 48(11):3118–3129. https://doi.org/10.1002/art.11303

    Article  Google Scholar 

  • Dunn TC, Lu Y, Jin H, Ries MD, Majumdar S (2004) T2 relaxation time of cartilage at MR imaging: comparison with severity of knee osteoarthritis. Radiology 232(2):592–598

    Article  Google Scholar 

  • Duvvuri U, Charagundla SR, Kudchodkar SB, Kaufman JH, Kneeland JB, Rizi R et al (2001) Human knee: in vivo T1ρ-weighted MR imaging at 1.5 T—preliminary experience. Radiology 220(3):822–826

    Article  Google Scholar 

  • Ehrenfest DMD, Andia I, Zumstein MA, Zhang CQ, Pinto NR, Bielecki T (2014) Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles Ligaments Tendons J 4(1):3

    Article  Google Scholar 

  • Elmorsy S, Funakoshi T, Sasazawa F, Todoh M, Tadano S, Iwasaki N (2014) Chondroprotective effects of high-molecular-weight cross-linked hyaluronic acid in a rabbit knee osteoarthritis model. Osteoarthr Cartil 22(1):121–127

    Article  Google Scholar 

  • Fan Z, Bau B, Yang H, Aigner T (2004) IL-1beta induction of IL-6 and LIF in normal articular human chondrocytes involves the ERK, p38 and NFkappaB signaling pathways. Cytokine 28(1):17–24. https://doi.org/10.1016/j.cyto.2004.06.003

    Article  Google Scholar 

  • Fanghänel J, Pera F, Anderhuber F, Nitsch R (2009) Waldeyerova anatomija čovjeka. Golden marketing - Tehnička knjiga, Zagreb

    Google Scholar 

  • Felson DT, McLaughlin S, Goggins J, LaValley MP, Gale ME, Totterman S et al (2003) Bone marrow edema and its relation to progression of knee osteoarthritis. Ann Intern Med 139(5_Part_1):330–336

    Article  Google Scholar 

  • Filardo G, Kon E, Di Martino A, Di Matteo B, Merli ML, Cenacchi A et al (2012) Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord 13(1):229

    Article  Google Scholar 

  • Forsey R, Fisher J, Thompson J, Stone M, Bell C, Ingham E (2006) The effect of hyaluronic acid and phospholipid based lubricants on friction within a human cartilage damage model. Biomaterials 27(26):4581–4590

    Article  Google Scholar 

  • Friedenstein AJ, Gorskaja JF, Kulagina NN (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 4(5):267–274

    Google Scholar 

  • Gray ML, Burstein D, Kim YJ, Maroudas A (2008) 2007 Elizabeth Winston Lanier Award Winner. Magnetic resonance imaging of cartilage glycosaminoglycan: basic principles, imaging technique, and clinical applications. J Orthop Res 26(3):281–291

    Article  Google Scholar 

  • Grigolo B, Lisignoli G, Desando G, Cavallo C, Marconi E, Tschon M et al (2009) Osteoarthritis treated with mesenchymal stem cells on hyaluronan-based scaffold in rabbit. Tissue Eng Part C Methods 15(4):647–658

    Article  Google Scholar 

  • Guermazi A, Roemer FW, Alizai H, Winalski CS, Welsch G, Brittberg M, Trattnig S (2015) State of the art: MR imaging after knee cartilage repair surgery. Radiology 277(1):23–43

    Article  Google Scholar 

  • Hangody L, Vásárhelyi G, Hangody LR, Sükösd Z, Tibay G, Bartha L, Bodó G (2008) Autologous osteochondral grafting—technique and long-term results. Injury 39(1):32–39

    Article  Google Scholar 

  • Harnly HW (2007) Microfracture: indications, technique, and results. Instr Course Lect 56:419–428

    Google Scholar 

  • Heijink A, Gomoll AH, Madry H, Drobnič M, Filardo G, Espregueira-Mendes J, Van Dijk CN (2012) Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 20(3):423–435

    Article  Google Scholar 

  • Hesper T, Hosalkar HS, Bittersohl D, Welsch GH, Krauspe R, Zilkens C, Bittersohl B (2014) T2∗ mapping for articular cartilage assessment: principles, current applications, and future prospects. Skelet Radiol 43(10):1429–1445

    Article  Google Scholar 

  • Hiraoka N, Takahashi Y, Arai K, Honjo S, Nakawaga S, Tsuchida S et al (2009) Hyaluronan and intermittent hydrostatic pressure synergistically suppressed MMP-13 and Il-6 expressions in osteoblasts from OA subchondral bone. Osteoarthr Cartil 17(1):S97

    Article  Google Scholar 

  • Hochberg MC, Zhan M, Langenberg P (2008) The rate of decline of joint space width in patients with osteoarthritis of the knee: a systematic review and meta-analysis of randomized placebo-controlled trials of chondroitin sulfate. Curr Med Res Opin 24:3029–3035

    Article  Google Scholar 

  • Holtzman DJ, Theologis AA, Carballido-Gamio J, Majumdar S, Li X, Benjamin C (2010) T1ρ and T2 quantitative magnetic resonance imaging analysis of cartilage regeneration following microfracture and mosaicplasty cartilage resurfacing procedures. J Magn Reson Imaging 32(4):914–923

    Article  Google Scholar 

  • Hudetz D, Borić I, Rod E, Jeleč Ž, Radić A, Vrdoljak T et al (2017) The effect of intra-articular injection of autologous microfragmented fat tissue on proteoglycan synthesis in patients with knee osteoarthritis. Genes 8(10):270

    Article  Google Scholar 

  • Hunter DJ, Zhang Y, Niu J, Goggins J, Amin S, LaValley MP et al (2006) Increase in bone marrow lesions associated with cartilage loss: a longitudinal magnetic resonance imaging study of knee osteoarthritis. Arthritis Rheum 54(5):1529–1535

    Article  Google Scholar 

  • Julovi SM, Yasuda T, Shimizu M, Hiramitsu T, Nakamura T (2004) Inhibition of interleukin-1beta-stimulated production of matrix metalloproteinases by hyaluronan via CD44 in human articular cartilage. Arthritis Rheum 50(2):516–525

    Article  Google Scholar 

  • Jüni P, Hari R, Rutjes AWS, Fischer R, Silletta MG, Reichenbach S, da Costa BR (2015) Intra‐articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev 22(10):CD005328. https://doi.org/10.1002/14651858.CD005328.pub3

    Article  Google Scholar 

  • Junqueira LC, Carneiro J (2005) Osnove histologije. Školska knjiga, Zagreb

    Google Scholar 

  • Kobayashi K, Matsuzaka S, Yoshida Y, Miyauchi S, Wada Y, Moriya H (2004) The effects of intraarticularly injected sodium hyaluronate on levels of intact aggrecan and nitric oxide in the joint fluid of patients with knee osteoarthritis. Osteoarthr Cartil 12(7):536–542

    Article  Google Scholar 

  • Koff MF, Amrami KK, Kaufman KR (2007) Clinical evaluation of T2 values of patellar cartilage in patients with osteoarthritis. Osteoarthr Cartil 15(2):198–204

    Article  Google Scholar 

  • Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE (2015) Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 23(5):1308–1316

    Article  Google Scholar 

  • Koller U, Apprich S, Schmitt B, Windhager R, Trattnig S (2017) Evaluating the cartilage adjacent to the site of repair surgery with glycosaminoglycan-specific magnetic resonance imaging. Int Orthop 41(5):969–974

    Article  Google Scholar 

  • Kon E, Buda R, Filardo G, Di Martino A, Timoncini A, Cenacchi A et al (2010) Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc 18(4):472–479. https://doi.org/10.1007/s00167-009-0940-8

    Article  Google Scholar 

  • Kreuz PC, Erggelet C, Steinwachs MR, Krause SJ, Lahm A, Niemeyer P et al (2006a) Is microfracture of chondral defects in the knee associated with different results in patients aged 40 years or younger? Arthroscopy 22(11):1180–1186

    Article  Google Scholar 

  • Kreuz PC, Steinwachs MR, Erggelet C, Krause SJ, Konrad G, Uhl M, Südkamp N (2006b) Results after microfracture of full-thickness chondral defects in different compartments in the knee. Osteoarthr Cartil 14(11):1119–1125

    Article  Google Scholar 

  • Krusche-Mandl I, Schmitt B, Zak L, Apprich S, Aldrian S, Juras V et al (2012) Long-term results 8 years after autologous osteochondral transplantation: 7 T gagCEST and sodium magnetic resonance imaging with morphological and clinical correlation. Osteoarthr Cartil 20(5):357–363

    Article  Google Scholar 

  • Kurkijärvi JE, Mattila L, Ojala RO, Vasara AI, Jurvelin JS, Kiviranta I, Nieminen MT (2007) Evaluation of cartilage repair in the distal femur after autologous chondrocyte transplantation using T2 relaxation time and dGEMRIC. Osteoarthr Cartil 15(4):372–378

    Article  Google Scholar 

  • Lajeunesse D, Delalandre A, Martel-Pelletier J, Pelletier J-P (2003) Hyaluronic acid reverses the abnormal synthetic activity of human osteoarthritic subchondral bone osteoblasts. Bone 33(4):703–710

    Article  Google Scholar 

  • Lee YH, Woo JH, Choi SJ, Ji JD, Song GG (2010) Effect of glucosamine or chondroitin sulfate on the osteoarthritis progression: a meta-analysis. Rheumatol Int 30:357–363

    Article  Google Scholar 

  • Leeb BF, Schweitzer H, Montag K, Smolen JS (2000) A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol 27:205–211

    Google Scholar 

  • Lin CS, Lue TF (2013) Defining vascular stem cells. Stem Cells Dev 22(7):1018–1026

    Article  Google Scholar 

  • Link TM, Neumann J, Li X (2017) Prestructural cartilage assessment using MRI. J Magn Reson Imaging 45(4):949–965

    Article  Google Scholar 

  • Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R et al (2013) A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol 9(1):30

    Article  Google Scholar 

  • Loeser RF (2003) Systemic and local regulation of articular cartilage metabolism: where does leptin fit in the puzzle? Arthritis Rheum 48(11):3009–3012. https://doi.org/10.1002/art.11315

    Article  Google Scholar 

  • Lopes Junior OV, Inacio AM (2013) Use of glucosamine and chondroitin to treat osteoarthritis: a review of the literature. Rev Bras Ortop 48(4):300–306

    Article  Google Scholar 

  • Lu HT, Sheu MT, Lin YF, Lan J, Chin YP, Hsieh MS et al (2013) Injectable hyaluronic-acid-doxycycline hydrogel therapy in experimental rabbit osteoarthritis. BMC Vet Res 9:68

    Article  Google Scholar 

  • Marlovits S, Singer P, Zeller P, Mandl I, Haller J, Trattnig S (2006) Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: determination of interobserver variability and correlation to clinical outcome after 2 years. Eur J Radiol 57(1):16–23

    Article  Google Scholar 

  • Marmotti A, Rossi R, Castoldi F, Roveda E, Michielon G, Peretti GM (2015) PRP and articular cartilage: a clinical update. Biomed Res Int 2015:542502

    Article  Google Scholar 

  • Martel-Pelletier J, Kwan Tat S, Pelletier JP (2010) Effects of chondroitin sulfate in the pathophysiology of the osteoarthritic joint: a narrative review. Osteoarthr Cartil 18(Suppl 1):S7–S11

    Article  Google Scholar 

  • McCarty M (1994) The neglect of glucosamine as treatment for osteoarthritis. A personal perspective. Med Hypotheses 42(5):323–327

    Article  Google Scholar 

  • McDonough AL (1982) Effects of corticosteroids on articular cartilage: a review of the literature. Phys Ther 62(6):835–839

    Article  Google Scholar 

  • Meenagh GK, Patton J, Kynes C, Wright GD (2004) A randomised controlled trial of intra-articular corticosteroid injection of the carpometacarpal joint of the thumb in osteoarthritis. Ann Rheum Dis 63(10):1260–1263

    Article  Google Scholar 

  • Miller BS, Steadman JR, Briggs KK, Rodrigo JJ, Rodkey WG (2004) Patient satisfaction and outcome after microfracture of the degenerative knee. J Knee Surg 17(01):13–17

    Article  Google Scholar 

  • Mlynarik V, Trattnig S, Huber M, Zembsch A, Imhof H (1999) The role of relaxation times in monitoring proteoglycan depletion in articular cartilage. J Magn Reson Imaging 10(4):497–502

    Article  Google Scholar 

  • Murphy JM, Fink DJ, Hunziker EB, Barry FP (2003) Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 48(12):3464–3474

    Article  Google Scholar 

  • Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH (2010) Autologous bone marrow–derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med 38(6):1110–1116

    Article  Google Scholar 

  • Neogi T, Felson D, Niu J, Lynch J, Nevitt M, Guermazi A et al (2009) Cartilage loss occurs in the same subregions as subchondral bone attrition: a within-knee subregion-matched approach from the multicenter osteoarthritis study. Arthritis Care Res 61(11):1539–1544

    Article  Google Scholar 

  • Osiris Therapeutics Announces Positive One Year (2007) Data from Chondrogen Trial for Knee Repair, Osiris Therapeutics. Inc., Ref. Type: Internet Communication

    Google Scholar 

  • Paschos NK, Sennett ML (2017) Update on mesenchymal stem cell therapies for cartilage disorders. World J Orthop 8(12):853

    Article  Google Scholar 

  • Peyron JG, Altman R (1992) Osteoarthritis: diagnosis and management. In: Howell DS, Moskowitz RW, Goldberg VM, Mankin HJ (eds) The epidemiology of osteoarthritis, vol 2. Saunders, Philadelphia, p 15

    Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147

    Article  Google Scholar 

  • Potter HG, Foo LF (2006) Magnetic resonance imaging of articular cartilage: trauma, degeneration, and repair. Am J Sports Med 34(4):661–677

    Article  Google Scholar 

  • Primorac D (1995) Reduced type II collagen mRNA in nanomelic cultured chondrocytes: an example of extracellular matrix/collagen feedback regulation? Croat Med J 36:85–92

    Google Scholar 

  • Primorac D, Stover ML, Clark SH, Rowe DW (1994) Molecular basis of nanomelia, a heritable chondrodystrophy of chicken. Matrix Biol 14(4):297–305

    Article  Google Scholar 

  • Raya JG (2015) Techniques and applications of in vivo diffusion imaging of articular cartilage. J Magn Reson Imaging 41(6):1487–1504

    Article  Google Scholar 

  • Raya JG, Melkus G, Adam-Neumair S, Dietrich O, Mützel E, Reiser MF et al (2013) Diffusion-tensor imaging of human articular cartilage specimens with early signs of cartilage damage. Radiology 266(3):831–841

    Article  Google Scholar 

  • Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O et al (2001) Long term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo controlled clinical trial. Lancet 357(9252):251–256

    Article  Google Scholar 

  • Richmond J, Hunter D, Irrgang J et al (2009) Treatment of osteoarthritis of the knee (nonarthroplasty). J Am Acad Orthop Surg 17:591–600

    Article  Google Scholar 

  • Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY (2003) Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 163(13):1514–1522

    Article  Google Scholar 

  • Roman-Blas JA, Herrero-Beaumont G (2014) Targeting subchondral bone in osteoporotic osteoarthritis. Arthritis Res Ther 16(6):494. https://doi.org/10.1186/s13075-014-0494-0

    Article  Google Scholar 

  • Ronca F, Palmieri L, Panicucci P, Ronca G (1998) Anti-inflammatory activity of chondroitin sulfate. Osteoarthr Cartil 6(Suppl A):14–21

    Article  Google Scholar 

  • Sakkas LI, Platsoucas CD (2007) The role of T cells in the pathogenesis of osteoarthritis. Arthritis Rheum 56(2):409–424. https://doi.org/10.1002/art.22369

    Article  Google Scholar 

  • Sasaki A, Sasaki K, Konttinen YT, Santavirta S, Takahara M, Takei H et al (2004) Hyaluronate inhibits the interleukin-1beta-induced expression of matrix metalloproteinase (MMP)-1 and MMP-3 in human synovial cells. Tohoku J Exp Med 204(2):99–107

    Article  Google Scholar 

  • Schneider U, Rackwitz L, Andereya S, Siebenlist S, Fensky F, Reichert J et al (2011) A prospective multicenter study on the outcome of type I collagen hydrogel–based autologous chondrocyte implantation (CaReS) for the repair of articular cartilage defects in the knee. Am J Sports Med 39(12):2558–2565

    Article  Google Scholar 

  • Schreiner MM, Mlynarik V, Zbýň Š, Szomolanyi P, Apprich S, Windhager R, Trattnig S (2017) New technology in imaging cartilage of the ankle. Cartilage 8(1):31–41

    Article  Google Scholar 

  • Singh A, Haris M, Cai K, Kassey VB, Kogan F, Reddy D et al (2012) Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T. Magn Reson Med 68(2):588–594

    Article  Google Scholar 

  • Sohn DH, Lottman LM, Lum LY, Kim SG, Pedowitz RA, Coutts RD, Sah RL (2002) Effect of gravity on localization of chondrocytes implanted in cartilage defects. Clin Orthop Relat Res 394:254–262

    Article  Google Scholar 

  • Stannus O, Jones G, Cicuttini F, Parameswaran V, Quinn S, Burgess J, Ding C (2010) Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthr Cartil 18(11):1441–1447. https://doi.org/10.1016/j.joca.2010.08.016

    Article  Google Scholar 

  • Steadman JR, Rodkey WG, Rodrigo JJ (2001) Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop Relat Res 391:S362–S369

    Article  Google Scholar 

  • Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG (2003) Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy 19(5):477–484

    Article  Google Scholar 

  • Steadman JR, Rodkey WG, Briggs KK (2010) Microfracture: its history and experience of the developing surgeon. Cartilage 1(2):78–86

    Article  Google Scholar 

  • Stolzing A, Jones E, McGonagle D, Scutt A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev 129(3):163–173

    Article  Google Scholar 

  • Tat SK, Pelletier JP, Vergés J, Lajeunesse D, Montell E, Fahmi H et al (2007) Chondroitin and glucosamine sulfate in combination decrease the pro-resorptive properties of human osteoarthritis subchondral bone osteoblasts: a basic science study. Arthritis Res Ther 9:R117

    Article  Google Scholar 

  • Tetteh ES, Bajaj S, Ghodadra NS, Cole BJ (2012) The basic science and surgical treatment options for articular cartilage injuries of the knee. J Orthop Sports Phys Ther 42(3):243–253

    Article  Google Scholar 

  • Towheed TE, Maxwell L, Judd MG et al (2006) Acetaminophen for osteoarthritis. Cochrane Database Syst Rev:D4257

    Google Scholar 

  • Trattnig S, Marlovits S, Gebetsroither S, Szomolanyi P, Welsch GH, Salomonowitz E et al (2007) Three-dimensional delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) for in vivo evaluation of reparative cartilage after matrix-associated autologous chondrocyte transplantation at 3.0 T: preliminary results. J Magn Reson Imaging 26(4):974–982

    Article  Google Scholar 

  • Trattnig S, Mamisch TC, Pinker K, Domayer S, Szomolanyi P, Marlovits S et al (2008) Differentiating normal hyaline cartilage from post-surgical repair tissue using fast gradient echo imaging in delayed gadolinium-enhanced MRI (dGEMRIC) at 3 Tesla. Eur Radiol 18(6):1251–1259

    Article  Google Scholar 

  • Trattnig S, Welsch GH, Juras V, Szomolanyi P, Mayerhoefer ME, Stelzeneder D et al (2010) 23Na MR imaging at 7 T after knee matrix–associated autologous chondrocyte transplantation preliminary results. Radiology 257(1):175–184

    Article  Google Scholar 

  • Tremolada C, Colombo V, Ventura C (2016) Adipose tissue and mesenchymal stem cells: state of the art and Lipogems® technology development. Curr Stem Cell Rep 2(3):304–312

    Article  Google Scholar 

  • US Food and Drug Administration (2004) FDA Public Health Advisory: Safety of Vioxx. FDA, Silver Spring. Available at http://www.fdagov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm106274htm. 25 September 2015

  • US Food and Drug Administration (2005) Information for Healthcare Professionals: Valdecoxib (marketed as Bextra). FDA, Silver Spring. Available at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124649.htm. 25 September 2015

  • US Food and Drug Administration Information for Healthcare Professionals: Celecoxib (Marketed as Celebrex) (2005) FDA, Silver Spring. Available at http://www.fda.gov/Drugs/DrugSafety/Postmarket DrugSafetyInformationforPatientsandProviders/ucm124655.htm. 25 September 2015

  • Uygur E, Kilic B, Demiroglu M, Ozkan K, Cift HT (2015) Subchondral bone and its role in osteoarthritis. Open J Orthopedics 5(11):355–360

    Article  Google Scholar 

  • van de Loo FA, Joosten LA, van Lent PL, Arntz OJ, van den Berg WB (1995) Role of interleukin-1, tumor necrosis factor alpha, and interleukin-6 in cartilage proteoglycan metabolism and destruction. Effect of in situ blocking in murine antigen- and zymosan-induced arthritis. Arthritis Rheum 38(2):164–172

    Article  Google Scholar 

  • Vega A, Martín-Ferrero MA, Del Canto F, Alberca M, García V, Munar A et al (2015) Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation 99(8):1681–1690

    Article  Google Scholar 

  • Wang L, Wu Y, Chang G, Oesingmann N, Schweitzer ME, Jerschow A, Regatte RR (2009) Rapid isotropic 3D-sodium MRI of the knee joint in vivo at 7T. J Magn Reson Imaging 30(3):606–614

    Article  Google Scholar 

  • Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF (2013) Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin 34(6):747

    Article  Google Scholar 

  • Welsch GH, Mamisch TC, Domayer SE, Dorotka R, Kutscha-Lissberg F, Marlovits S et al (2008a) Cartilage T2 assessment at 3-T MR imaging: in vivo differentiation of normal hyaline cartilage from reparative tissue after two cartilage repair procedures—initial experience. Radiology 247(1):154–161

    Article  Google Scholar 

  • Welsch GH, Mamisch TC, Hughes T, Zilkens C, Quirbach S, Scheffler K et al (2008b) In vivo biochemical 7.0 Tesla magnetic resonance: preliminary results of dGEMRIC, zonal T2, and T2∗ mapping of articular cartilage. Investig Radiol 43(9):619–626

    Article  Google Scholar 

  • Wildi L, Raynauld J, Martel-Pelletier J, Beaulieu A, Bessette L (2011) Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomized, double-blind, placebo-controlled pilot study using MRI. Ann Rheum Dis 70:982–989

    Article  Google Scholar 

  • Williams A, Gillis A, McKenzie C, Po B, Sharma L, Micheli L et al (2004) Glycosaminoglycan distribution in cartilage as determined by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC): potential clinical applications. Am J Roentgenol 182(1):167–172

    Article  Google Scholar 

  • Wluka AE, Hanna F, Davies-Tuck M, Wang Y, Bell RJ, Davis SR et al (2009) Bone marrow lesions predict increase in knee cartilage defects and loss of cartilage volume in middle-aged women without knee pain over 2 years. Ann Rheum Dis 68(6):850–855

    Article  Google Scholar 

  • Young AA, Stanwell P, Williams A, Rohrsheim JA, Parker DA, Giuffre B, Ellis AM (2005) Glycosaminoglycan content of knee cartilage following posterior cruciate ligament rupture demonstrated by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC): a case report. J Bone Joint Surg Am 87(12):2763–2767

    Article  Google Scholar 

  • Zaslav K, Cole B, Brewster R, DeBerardino T, Farr J, Fowler P, Nissen C (2009) A prospective study of autologous chondrocyte implantation in patients with failed prior treatment for articular cartilage defect of the knee results of the study of the treatment of articular repair (STAR) clinical trial. Am J Sports Med 37(1):42–55

    Article  Google Scholar 

  • Zbýň Š, Stelzeneder D, Welsch GH, Negrin LL, Juras V, Mayerhoefer ME et al (2012) Evaluation of native hyaline cartilage and repair tissue after two cartilage repair surgery techniques with 23Na MR imaging at 7 T: initial experience. Osteoarthr Cartil 20(8):837–845

    Article  Google Scholar 

  • Zeng C, Wei J, Li H, Wang Y, Xie D, Yang T et al (2015) Effectiveness and safety of glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of osteoarthritis of the knee. Sci Rep 5:16827

    Article  Google Scholar 

  • Zhang W, Jones A, Doherty M (2004) Does paracetamol (acetaminophen) reduce the pain of osteoarthritis? A meta-analysis of randomised controlled trials. Ann Rheum Dis 63:901–907

    Article  Google Scholar 

  • Zhang W, Moskowitz RW, Nuki G et al (2008a) OARSI recommendations for the management of hip and knee osteoarthritis, part I: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil 16:137–162

    Article  Google Scholar 

  • Zhang W, Moskowitz RW, Nuki G et al (2008b) OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil 16:137–162

    Article  Google Scholar 

  • Zhen G, Wen C, Jia X, Li Y, Crane JL, Mears SC et al (2013) Inhibition of TGF-beta signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. Nat Med 19(6):704–712. https://doi.org/10.1038/nm.3143

    Article  Google Scholar 

  • Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H et al (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13(12):4279–4295

    Article  Google Scholar 

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Authors and Affiliations

  1. St. Catherine Specialty Hospital, Zagreb, Croatia

    Damir Hudetz, Željko Jeleč, Eduard Rod, Igor Borić, Mihovil Plečko & Dragan Primorac

  2. Clinical Hospital “Sveti Duh”, Zagreb, Croatia

    Damir Hudetz

  3. School of Medicine, JJ Strossmayer University of Osijek, Osijek, Croatia

    Damir Hudetz, Željko Jeleč, Eduard Rod & Dragan Primorac

  4. School of Medicine, University of Split, Split, Croatia

    Igor Borić & Dragan Primorac

  5. School of Medicine, University of Rijeka, Rijeka, Croatia

    Igor Borić

  6. Gen-Info, Zagreb, Croatia

    Dragan Primorac

  7. Children’s Hospital Srebrnjak, Zagreb, Croatia

    Dragan Primorac

  8. Eberly College of Science, The Pennsylvania State University, University Park, State College, PA, USA

    Dragan Primorac

  9. The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, West Haven, CT, USA

    Dragan Primorac

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    Nada Bodiroga-Vukobrat

  2. Croatian Academy of Sciences and Arts, Rijeka, Croatia

    Daniel Rukavina

  3. Juraj Dobrila University of Pula, Faculty of Medicine, Pula, Croatia

    Krešimir Pavelić

  4. Department of Biotechnology, Centre for High-Throughput Technologies, University of Rijeka, Rijeka, Croatia

    Krešimir Pavelić

  5. University of Applied Sciences, Ludwigsburg, Germany

    Gerald G. Sander

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Hudetz, D., Jeleč, Ž., Rod, E., Borić, I., Plečko, M., Primorac, D. (2019). The Future of Cartilage Repair. In: Bodiroga-Vukobrat, N., Rukavina, D., Pavelić, K., Sander, G.G. (eds) Personalized Medicine in Healthcare Systems. Europeanization and Globalization, vol 5. Springer, Cham. https://doi.org/10.1007/978-3-030-16465-2_29

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