Advances for Treatment of Knee OC Defects

  • Marta OndrésikEmail author
  • J. Miguel Oliveira
  • Rui L. Reis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1059)


Osteochondral (OC) defects are prevalent among young adults and are notorious for being unable to heal. Although they are traumatic in nature, they often develop silently. Detection of many OC defects is challenging, despite the criticality of early care. Current repair approaches face limitations and cannot provide regenerative or long-standing solution. Clinicians and researchers are working together in order to develop approaches that can regenerate the damaged tissues and protect the joint from developing osteoarthritis. The current concepts of tissue engineering and regenerative medicine, which have brought many promising applications to OC management, are overviewed herein. We will also review the types of stem cells that aim to provide sustainable cell sources overcoming the limitation of autologous chondrocyte-based applications. The various scaffolding materials that can be used as extracellular matrix mimetic and having functional properties similar to the OC unit are also discussed.


Osteochondral defects Osteochondral tissue engineering Regenerative medicine Chondrocytes Stem cell therapy iPS cells Scaffold design and Bilayered scaffolds 


  1. 1.
    Ding C, Cicuttini F, Scott F et al (2005) The genetic contribution and relevance of knee cartilage defects: case-control and sib-pair studies. J Rheumatol 32:1937–1942PubMedGoogle Scholar
  2. 2.
    Hjelle K, Solheim E, Strand T et al (2002) Articular cartilage defects in 1,000 knee arthroscopies. Arthroscopy 18:730–734. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Widuchowski W, Widuchowski J, Trzaska T (2007) Articular cartilage defects: study of 25,124 knee arthroscopies. Knee 14:177–182. CrossRefPubMedGoogle Scholar
  4. 4.
    Brittberg M, Lindahl A, Nilsson A et al (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331:889–895. CrossRefPubMedGoogle Scholar
  5. 5.
    Kocher MS, Tucker R, Ganley TJ, Flynn JM (2006) Management of osteochondritis dissecans of the knee. Am J Sports Med 34:1181–1191. CrossRefPubMedGoogle Scholar
  6. 6.
    Espregueira-Mendes J, Pereira H, Sevivas N et al (2012) Assessment of rotatory laxity in anterior cruciate ligament-deficient knees using magnetic resonance imaging with Porto-knee testing device. Knee Surg Sports Traumatol Arthrosc 20:671–678. CrossRefPubMedGoogle Scholar
  7. 7.
    Lee JE, Ryu KN, Park JS et al (2014) Osteochondral lesion of the bilateral femoral heads in a young athletic patient. Korean J Radiol 15(6):792. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Cahill (1995) Osteochondritis dissecans of the knee: treatment of juvenile and adult forms. J Am Acad Orthop Surg 3:237–247CrossRefPubMedGoogle Scholar
  9. 9.
    Eckstein F, Cicuttini F, Raynauld J-P et al (2006) Magnetic resonance imaging (MRI) of articular cartilage in knee osteoarthritis (OA): morphological assessment. Osteoarthritis Cartilage 14 Suppl A:A46–A75. CrossRefPubMedGoogle Scholar
  10. 10.
    Ryd L, Brittberg M, Eriksson K et al (2015) Pre-osteoarthritis: definition and diagnosis of an elusive clinical entity. Cartilage 6:156. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Durur-Subasi I, Durur-Karakaya A, Yildirim OS (2015) Osteochondral lesions of major joints. Eurasian J Med 47:138–144. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Outerbridge RE (1961) The etiology of chondromalacia patellae. J Bone Jt Surg 43:752–757CrossRefGoogle Scholar
  13. 13.
    da Cunha Cavalcanti FM, Doca D, Cohen M, Ferretti M (2012) Updating on diagnosis and treatment of chondral lesion of the knee. Rev Bras Ortop 47:12–20. CrossRefPubMedGoogle Scholar
  14. 14.
    Brittberg M, Winalski CS (2003) Evaluation of cartilage injuries and repair. J Bone Joint Surg Am 85-A(Suppl 2):58–69CrossRefGoogle Scholar
  15. 15.
    Magnussen RA, Dunn WR, Carey JL, Spindler KP (2008) Treatment of focal articular cartilage defects in the knee: a systematic review. Clin Orthop Relat Res 466:952–962. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Seo S-S, Kim C-W, Jung D-W (2011) Management of focal chondral lesion in the knee joint. Knee Surg Relat Res 23:185–196. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kurtz S, Ong K, Lau E et al (2007) Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 89:780–785. CrossRefPubMedGoogle Scholar
  18. 18.
    Kim J, Nakamura N, Brittberg M (2014) Techniques in cartilage repair surgery. CrossRefGoogle Scholar
  19. 19.
    Last RJ (1948) Some anatomical details of the knee joint. J Bone Joint Surg Br 30B:683–688CrossRefPubMedGoogle Scholar
  20. 20.
    Akizuki S, Mow VC, Müller F et al (1986) Tensile properties of human knee joint cartilage: I. Influence of ionic conditions, weight bearing, and fibrillation on the tensile modulus. J Orthop Res 4:379–392. CrossRefPubMedGoogle Scholar
  21. 21.
    Hasler EM, Herzog W, Wu JZ et al (1999) Articular cartilage biomechanics: theoretical models, material properties, and biosynthetic response. Crit Rev Biomed Eng 27:415–488PubMedGoogle Scholar
  22. 22.
    Ralphs JR, Benjamin M (1994) The joint capsule: structure, composition, ageing and disease. J Anat 184:503–509PubMedPubMedCentralGoogle Scholar
  23. 23.
    Wilson R, Diseberg AF, Gordon L et al (2010) Comprehensive profiling of cartilage extracellular matrix formation and maturation using sequential extraction and label-free quantitative proteomics. Mol Cell Proteomics 9:1296–1313. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Fujie H, Nakamura N (2013) Frictional properties of articular cartilage-like tissues repaired with a mesenchymal stem cell-based tissue engineered construct. Conf Proc IEEE Eng Med Biol Soc. 2013:401–404Google Scholar
  25. 25.
    Thambyah A, Nather A, Goh J (2006) Mechanical properties of articular cartilage covered by the meniscus. Osteoarthr Cartil 14:580–588. CrossRefPubMedGoogle Scholar
  26. 26.
    Goldring MB (2012) Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis. Ther Adv Musculoskelet Dis 4:269–285. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Kheir E, Shaw D (2009) Hyaline articular cartilage. Orthop Trauma 23:450–455. CrossRefGoogle Scholar
  28. 28.
    Bhosale AM, Richardson JB (2008) Articular cartilage: structure, injuries and review of management. Br Med Bull 87:77–95. CrossRefPubMedGoogle Scholar
  29. 29.
    Kiani CH, Chen LI, Wu YJ et al (2002) Structure and function of aggrecan 12:19–32Google Scholar
  30. 30.
    Li J, Anemaet W, M a D et al (2011) Knockout of ADAMTS5 does not eliminate cartilage aggrecanase activity but abrogates joint fibrosis and promotes cartilage aggrecan deposition in murine osteoarthritis models. J Orthop Res 29:516–522. CrossRefPubMedGoogle Scholar
  31. 31.
    Lu XL, Mow VC (2008) Biomechanics of articular cartilage and determination of material properties. Med Sci Sports Exerc 40:193–199. CrossRefPubMedGoogle Scholar
  32. 32.
    Bock HC, Michaeli P, Bode C et al (2001) The small proteoglycans decorin and biglycan in human articular cartilage of late-stage osteoarthritis. Osteoarthr Cartil 9:654–663. CrossRefPubMedGoogle Scholar
  33. 33.
    Jay GD, Tantravahi U, Britt DE et al (2001) Homology of lubricin and superficial zone protein (SZP): products of megakaryocyte stimulating factor (MSF) gene expression by human synovial fibroblasts and articular chondrocytes localized to chromosome 1q25. J Orthop Res 19:677–687. CrossRefPubMedGoogle Scholar
  34. 34.
    Sophia Fox AJ, Bedi A, Rodeo SA (2009) The basic science of articular cartilage: structure, composition, and function. Sports Health 1:461–468. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Eyre DR, Weis MA, Wu JJ (2006) Articular cartilage collagen: an irreplaceable framework? Eur Cells Mater 12:57–63. CrossRefGoogle Scholar
  36. 36.
    Eyre D (2002) Collagen of articular cartilage. Arthritis Res 4:30–35CrossRefPubMedGoogle Scholar
  37. 37.
    Bayliss MT, Venn M, Maroudas A, Ali SY (1983) Structure of proteoglycans from different layers of human articular cartilage. Biochem J 209:387–400CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Zhytkova MA, Chizhik SA, Wierzcholski K et al (2010) Properties of cartilage on micro- and nanolevel. Adv Tribol.
  39. 39.
    Redler I, Mow VC, Zimny ML, Mansell J (1975) The ultrastructure and biomechanical significance of the tidemark of articular cartilage. Clin Orthop Relat Res:357–362CrossRefGoogle Scholar
  40. 40.
    Lories RJ, Luyten FP (2011) The bone-cartilage unit in osteoarthritis. Nat Rev Rheumatol 7:43–49. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Duncan H, Jundt J, Riddle JM et al (1987) The tibial subchondral plate. A scanning electron microscopic study. J Bone Joint Surg Am 69:1212–1220CrossRefPubMedGoogle Scholar
  42. 42.
    Lyons TJ, Stoddart RW, McClure SF, McClure J (2005) The tidemark of the chondro-osseous junction of the normal human knee joint. J Mol Histol 36:207–215. CrossRefPubMedGoogle Scholar
  43. 43.
    Eyre DR, Wu JJ (1995) Collagen structure and cartilage matrix integrity. J Rheumatol Suppl 43:82–85PubMedGoogle Scholar
  44. 44.
    Buckwalter JA, Mankin HJ (1998) Articular cartilage: tissue design and chondrocyte-matrix interactions. Instr Course Lect 47:477–486PubMedGoogle Scholar
  45. 45.
    Goldring MB, Goldring SR (2010) Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci 1192:230–237. CrossRefPubMedGoogle Scholar
  46. 46.
    Obeid EM, Adams MA, Newman JH (1994) Mechanical properties of articular cartilage in knees with unicompartmental osteoarthritis. J Bone Joint Surg Br 76:315–319CrossRefPubMedGoogle Scholar
  47. 47.
    Pan J, Wang B, Li W et al (2012) Elevated cross-talk between subchondral bone and cartilage in osteoarthritic joints. Bone 51:212–217. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Sharma AR, Jagga S, Lee S-S, Nam J-S (2013) Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis. Int J Mol Sci 14:19805–19830. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Bentley G, Bhamra JS, Gikas PD et al (2013) Repair of osteochondral defects in joints-how to achieve success. Injury 44:S3–S10. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Oei EHG, Van Tiel J, Robinson WH, Gold GE (2014) Quantitative radiologic imaging techniques for articular cartilage composition: toward early diagnosis and development of disease-modifying therapeutics for osteoarthritis. Arthritis Care Res 66:1129–1141. CrossRefGoogle Scholar
  51. 51.
    Wenham CYJ, Conaghan PG (2009) Imaging the painful osteoarthritic knee joint: what have we learned? Nat Clin Pract Rheumatol 5:149–158. CrossRefPubMedGoogle Scholar
  52. 52.
    Braun HJ, Gold GE (2012) Diagnosis of osteoarthritis: imaging. Bone 51:278–288. CrossRefPubMedGoogle Scholar
  53. 53.
    Van Tiel J, Reijman M, Bos PK et al (2013) Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) shows no change in cartilage structural composition after viscosupplementation in patients with early-stage knee osteoarthritis. PLoS One 8:e79785. CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Lusic H, Grinstaff MW (2013) X-ray-computed tomography contrast agents. Chem Rev 113:1641–1666. CrossRefPubMedGoogle Scholar
  55. 55.
    Shafieyan Y, Khosravi N, Moeini M, Quinn TM (2014) Diffusion of MRI and CT contrast agents in articular cartilage under static compression. Biophys J 107:485–492. CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Lee N, Hyeon T (2012) Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents. Chem Soc Rev 41:2575–2589. CrossRefPubMedGoogle Scholar
  57. 57.
    Zhu D, Liu F, Ma L et al (2013) Nanoparticle-based systems for T1-weighted magnetic resonance imaging contrast agents. Int J Mol Sci 14:10591–10607. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 99:2293–2352CrossRefPubMedGoogle Scholar
  59. 59.
    Wiewiorski M, Miska M, Kretzschmar M et al (2013) Delayed gadolinium-enhanced MRI of cartilage of the ankle joint: results after autologous matrix-induced chondrogenesis (AMIC)-aided reconstruction of osteochondral lesions of the talus. Clin Radiol 68:1031–1038. CrossRefPubMedGoogle Scholar
  60. 60.
    Freedman JD, Lusic H, Wiewiorski M et al (2015) A cationic gadolinium contrast agent for magnetic resonance imaging of cartilage. Chem Commun (Camb) 51:11166–11169. CrossRefGoogle Scholar
  61. 61.
    Filardo G, Kon E, Di Martino A et al (2012) Second-generation arthroscopic autologous chondrocyte implantation for the treatment of degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc 20:1704–1713. CrossRefPubMedGoogle Scholar
  62. 62.
    Piontek T, Ciemniewska-Gorzela K, Szulc A et al (2012) All-arthroscopic AMIC procedure for repair of cartilage defects of the knee. Knee Surgery, Sport Traumatol Arthrosc 20:922–925. CrossRefGoogle Scholar
  63. 63.
    Rodrigues MT, Gomes ME, Reis RL (2011) Current strategies for osteochondral regeneration: from stem cells to pre-clinical approaches. Curr Opin Biotechnol 22:726–733. CrossRefPubMedGoogle Scholar
  64. 64.
    Karkabi S, Rosenberg N (2015) Arthroscopic debridement with lavage and arthroscopic lavage only as the treatment of symptomatic osteoarthritic knee. Open J Clin Diagnostics 05:68–73. CrossRefGoogle Scholar
  65. 65.
    Steadman JR, Rodkey WG, Briggs KK (2010) Microfracture: its history and experience of the developing surgeon. Cartilage 1:78–86. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Torrie AM, Kesler WW, Elkin J, Gallo RA (2015) Osteochondral allograft. Curr Rev Musculoskelet Med 8:413–422. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Espregueira-Mendes J, Pereira H, Sevivas N et al (2012) Osteochondral transplantation using autografts from the upper tibio-fibular joint for the treatment of knee cartilage lesions. Knee Surg Sports Traumatol Arthrosc 20:1136–1142. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Health Quality Ontario (2005) Arthroscopic lavage and debridement for osteoarthritis of the knee: an evidence-based analysis. Ont Health Technol Assess Ser 5:1–37PubMedCentralGoogle Scholar
  69. 69.
    Segal NA, Buckwalter JA, Amendola A (2006) Other surgical techniques for osteoarthritis. Best Pract Res Clin Rheumatol 20:155–176. CrossRefPubMedGoogle Scholar
  70. 70.
    Chen H, Sun J, Hoemann CD et al (2009) Drilling and microfracture lead to different bone structure and necrosis during bone-marrow stimulation for cartilage repair. J Orthop Res 27:1432–1438. CrossRefPubMedGoogle Scholar
  71. 71.
    Steadman JR, Rodkey WG, Briggs KK, Rodrigo JJ (1999) The microfracture technic in the management of complete cartilage defects in the knee joint. Orthopade 28:26. CrossRefPubMedGoogle Scholar
  72. 72.
    Steadman JR, Rodkey WG, Singleton SB, Briggs KK (1997) Microfracture technique for full-thickness chondral defects: technique and clinical results. Oper Tech Orthop 7:300–304. CrossRefGoogle Scholar
  73. 73.
    Steadman JR, Rodkey WG, Rodrigo JJ (2001) Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop Relat Res 391:S362–S369CrossRefGoogle Scholar
  74. 74.
    Gadjanski I, Vunjak-Novakovic G (2015) Challenges in engineering osteochondral tissue grafts with hierarchical structures. Expert Opin Biol Ther 15:1583–1599. CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Hangody L, Kish G, Kárpáti Z et al (1997) Arthroscopic autogenous osteochondral mosaicplasty for the treatment of femoral condylar articular defects. Knee Surgery, Sport Traumatol Arthrosc 5:262–267. CrossRefGoogle Scholar
  76. 76.
    Bobić V (1996) Arthroscopic osteochondral autograft transplantation in anterior cruciate ligament reconstruction: a preliminary clinical study. Knee Surg Sports Traumatol Arthrosc 3(4):262CrossRefPubMedGoogle Scholar
  77. 77.
    Makris EA, Gomoll AH, Malizos KN et al (2014) Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol.
  78. 78.
    Nooeaid P, Salih V, Beier JP, Boccaccini AR (2012) Osteochondral tissue engineering: scaffolds, stem cells and applications. J Cell Mol Med 16:2247–2270. CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Foldager CB (2013) Advances in autologous chondrocyte implantation and related techniques for cartilage repair. Dan Med J 60:B4600PubMedGoogle Scholar
  80. 80.
    Diaz-romero J, Nesic D, Grogan SP et al (2008) Immunophenotypic changes of human articular chondrocytes during monolayer culture reflect bona fide dedifferentiation rather than amplification of progenitor. J Cell Physiol 214(1):75–83. CrossRefGoogle Scholar
  81. 81.
    Tseng A, Pomerantseva I, Cronce MJ et al (2014) Extensively expanded auricular chondrocytes form neocartilage in vivo. Cartilage 5:241–251. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Ma B, Leijten JCH, Wu L et al (2013) Gene expression profiling of dedifferentiated human articular chondrocytes in monolayer culture. Osteoarthr Cartil 21:599–603. CrossRefPubMedGoogle Scholar
  83. 83.
    Leijten JCH, Georgi N, Wu L et al (2013) Cell sources for articular cartilage repair strategies: shifting from monocultures to cocultures. Tissue Eng Part B Rev 19:31–40. CrossRefPubMedGoogle Scholar
  84. 84.
    Hubka KM, Dahlin RL, Meretoja VV et al (2014) Enhancing chondrogenic phenotype for cartilage tissue engineering: monoculture and coculture of articular chondrocytes and mesenchymal stem cells. Tissue Eng Part B Rev 20:641–654. CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Panseri S, Russo A, Cunha C et al (2012) Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration. Knee Surg Sports Traumatol Arthrosc 20:1182–1191. CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr Cartil 10:432–463. CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Caplan a I, Bruder SP (2001) Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends Mol Med 7:259–264CrossRefPubMedGoogle Scholar
  88. 88.
    Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317. CrossRefGoogle Scholar
  89. 89.
    Wang M, Yuan Z, Ma N et al (2017) Advances and prospects in stem cells for cartilage regeneration. Stem Cells Int 2017:1–16. CrossRefGoogle Scholar
  90. 90.
    Bourin P, Bunnell BA, Casteilla L et al (2013) Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 15:641–648. CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Sakaguchi Y, Sekiya I, Yagishita K, Muneta T (2005) Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum 52:2521–2529. CrossRefPubMedGoogle Scholar
  92. 92.
    Schumacher BL, Hughes CE, Kuettner KE et al (1999) Immunodetection and partial cDNA sequence of the proteoglycan, superficial zone protein, synthesized by cells lining synovial joints. J Orthop Res 17:110–120. CrossRefPubMedGoogle Scholar
  93. 93.
    Zhou C, Zheng H, Seol D et al (2014) Gene expression profiles reveal that chondrogenic progenitor cells and synovial cells are closely related. J Orthop Res 32:981–988. CrossRefPubMedGoogle Scholar
  94. 94.
    Pei M, Li JT, Shoukry M, Zhang Y (2011) A review of decellularized stem cell matrix: a novel cell expansion system for cartilage tissue engineering. Eur Cell Mater 22:333–343. discussion 343CrossRefPubMedGoogle Scholar
  95. 95.
    Pei M, He F (2012) Extracellular matrix deposited by synovium-derived stem cells delays replicative senescent chondrocyte dedifferentiation and enhances redifferentiation. J Cell Physiol 227:2163–2174. CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Ando W, Tateishi K, Katakai D et al (2008) In vitro generation of a scaffold-free tissue-engineered construct (TEC) derived from human synovial mesenchymal stem cells: biological and mechanical properties and further chondrogenic potential. Tissue Eng Part A 14:2041–2049. CrossRefPubMedGoogle Scholar
  97. 97.
    Vonk LA, de Windt TS, Slaper-Cortenbach ICM, Saris DBF (2015) Autologous, allogeneic, induced pluripotent stem cell or a combination stem cell therapy? Where are we headed in cartilage repair and why: a concise review. Stem Cell Res Ther 6:94. CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Zuk PA, Zhu M, Ashjian P et al (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295. CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Puetzer JL, Petitte JN, Loboa EG (2010) Comparative review of growth factors for induction of three-dimensional in vitro chondrogenesis in human mesenchymal stem cells isolated from bone marrow and adipose tissue. Tissue Eng Part B Rev 16:435–444. CrossRefPubMedGoogle Scholar
  100. 100.
    Mehlhorn AT, Niemeyer P, Kaschte K et al (2007) Differential effects of BMP-2 and TGF-beta1 on chondrogenic differentiation of adipose derived stem cells. Cell Prolif 40:809–823. CrossRefPubMedGoogle Scholar
  101. 101.
    Schelbergen RF, van Dalen S, ter Huurne M et al (2014) Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis is driven by high synovial activation and reflected by S100A8/A9 serum levels. Osteoarthr Cartil 22:1158–1166. CrossRefPubMedGoogle Scholar
  102. 102.
    Mardani M, Hashemibeni B, Ansar MM et al (2013) Comparison between chondrogenic markers of differentiated chondrocytes from adipose derived stem cells and articular chondrocytes in vitro. Iran J Basic Med Sci 16:763–773PubMedPubMedCentralGoogle Scholar
  103. 103.
    Hildner F, Albrecht C, Gabriel C et al (2011) State of the art and future perspectives of articular cartilage regeneration : a focus on adipose-derived stem cells and platelet-derived products. J Tissue Eng Regen Med 5:36–51. CrossRefGoogle Scholar
  104. 104.
    Diekmann B, Rowland C, DP L (2010) Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix. Tissue Eng Part A 16:523–533CrossRefGoogle Scholar
  105. 105.
    RA O (2012) Cell sources for the regeneration of articular cartilage: the past, the horizon and the future. Int J Exp Pathol 93:389–400. CrossRefGoogle Scholar
  106. 106.
    Kobayashi Y, Okada Y, Itakura G et al (2012) Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity. PLoS One 7:e52787. CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. CrossRefGoogle Scholar
  108. 108.
    Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872. CrossRefGoogle Scholar
  109. 109.
    Singh VK, Kalsan M, Kumar N et al (2015) Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front Cell Dev Biol 3:2. CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Medvedev SP, Grigor’eva EV, Shevchenko AI et al (2011) Human induced pluripotent stem cells derived from fetal neural stem cells successfully undergo directed differentiation into cartilage. Stem Cells Dev 20:1099–1112. CrossRefPubMedGoogle Scholar
  111. 111.
    Wei Y, Zeng W, Wan R et al (2012) Chondrogenic differentiation of induced pluripotent stem cells from osteoarthritic chondrocytes in alginate matrix. Eur Cell Mater 23:1–12CrossRefPubMedGoogle Scholar
  112. 112.
    Hiramatsu K, Sasagawa S, Outani H et al (2011) Generation of hyaline cartilaginous tissue from mouse adult dermal fibroblast culture by defined factors. J Clin Invest 121:640–657. CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Outani H, Okada M, Yamashita A et al (2013) Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors. PLoS One 8:e77365. CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Salgado AJ, Oliveira JM, Martins A et al (2013) Tissue engineering and regenerative medicine: past, present, and future. Int Rev Neurobiol.
  115. 115.
    Mano JF, Silva GA, Azevedo HS et al (2007) Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends. J R Soc Interface 4:999–1030. CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Kobayashi S, Fujikawa S-i, Ohmae M (2003) Enzymatic synthesis of chondroitin and its derivatives catalyzed by hyaluronidase. J. Am. Chem. Soc. 125(47):14357–14369. CrossRefPubMedGoogle Scholar
  117. 117.
    Silva TH, Alves A, Popa EG et al (2012) Marine algae sulfated polysaccharides for tissue engineering and drug delivery approaches. Biomatter 2:278–289. CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Yan LP, Oliveira JM, Oliveira AL, Reis RL (2013) Silk fibroin/nano-CaP bilayered scaffolds for osteochondral tissue engineering. Key Eng Mater 587:245–248. CrossRefGoogle Scholar
  119. 119.
    Yang C, Hillas PJ, Julio AB et al (2004) The application of recombinant human collagen in tissue engineering. BioDrugs 18:103–119CrossRefPubMedGoogle Scholar
  120. 120.
    Rutgers M, Saris DB, Vonk LA et al (2013) Effect of collagen type I or type II on chondrogenesis by cultured human articular chondrocytes. Tissue Eng Part A 19:59–65. CrossRefPubMedGoogle Scholar
  121. 121.
    Burdick JA, Mauck RL (2010) Biomaterials for tissue engineering applications: a review of the past and future trends. Springer Science & Business Media, AustriaGoogle Scholar
  122. 122.
    Parenteau-Bareil R, Gauvin R, Berthod F (2010) Collagen-based biomaterials for tissue engineering applications. Materials (Basel) 3:1863–1887. CrossRefGoogle Scholar
  123. 123.
    Grant GT, Morris ER, Rees DA et al (1973) Biological interactions between polysaccharides and divalent cations: the egg-box model. FEBS Lett 32:195–198. CrossRefGoogle Scholar
  124. 124.
    Petrenko YA, Ivanov RV, Petrenko AY, Lozinsky VI (2011) Coupling of gelatin to inner surfaces of pore walls in spongy alginate-based scaffolds facilitates the adhesion, growth and differentiation of human bone marrow mesenchymal stromal cells. J Mater Sci Mater Med 22:1529–1540. CrossRefPubMedGoogle Scholar
  125. 125.
    Bonaventure J, Kadhom N, Cohen-Solal L et al (1994) Reexpression of cartilage-specific genes by dedifferentiated human articular chondrocytes cultured in alginate beads. Exp Cell Res 212:97–104. CrossRefPubMedGoogle Scholar
  126. 126.
    Abarrategi A, Lópiz-Morales Y, Ramos V et al (2010) Chitosan scaffolds for osteochondral tissue regeneration. J Biomed Mater Res Part A 95A:1132–1141. CrossRefGoogle Scholar
  127. 127.
    Deng Y, Ren J, Chen G et al (2017) Injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for abdominal tissue regeneration. Sci Rep 7:2699. CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Yan L-P, Oliveira JM, Oliveira AL, Reis RL (2015) In vitro evaluation of the biological performance of macro/micro-porous silk fibroin and silk-nano calcium phosphate scaffolds. J Biomed Mater Res B Appl Biomater 103:888–898. CrossRefPubMedGoogle Scholar
  129. 129.
    Yan L-P, Silva-Correia J, Oliveira MB et al (2015) Bilayered silk/silk-nanoCaP scaffolds for osteochondral tissue engineering: in vitro and in vivo assessment of biological performance. Acta Biomater 12:227–241. CrossRefPubMedPubMedCentralGoogle Scholar
  130. 130.
    Ondrésik M, Azevedo Maia FR, da Silva Morais A et al (2017) Management of knee osteoarthritis. Current status and future trends. Biotechnol Bioeng 114:717–739. CrossRefPubMedGoogle Scholar
  131. 131.
    Antunes JC, Oliveira JM, Reis RL et al (2010) Novel poly(L-lactic acid)/hyaluronic acid macroporous hybrid scaffolds: characterization and assessment of cytotoxicity. J Biomed Mater Res A 94:856–869. CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Wright LD, McKeon-Fischer KD, Cui Z et al (2014) PDLA/PLLA and PDLA/PCL nanofibers with a chitosan-based hydrogel in composite scaffolds for tissue engineered cartilage. J Tissue Eng Regen Med 8:946–954. CrossRefPubMedGoogle Scholar
  133. 133.
    Liu W, Li Z, Zheng L et al (2016) Electrospun fibrous silk fibroin/poly(L-lactic acid) scaffold for cartilage tissue engineering. Tissue Eng Regen Med 13:516–526. CrossRefGoogle Scholar
  134. 134.
    Miljkovic ND, Cooper GM, Marra KG (2008) Chondrogenesis, bone morphogenetic protein-4 and mesenchymal stem cells. Osteoarthr Cartil 16:1121–1130. CrossRefPubMedGoogle Scholar
  135. 135.
    Samavedi S, Whittington AR, Goldstein AS (2013) Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior. Acta Biomater 9:8037–8045. CrossRefPubMedGoogle Scholar
  136. 136.
    Trombetta R, Inzana JA, Schwarz EM et al (2017) 3D printing of calcium phosphate ceramics for bone tissue engineering and drug delivery. Ann Biomed Eng 45:23–44. CrossRefPubMedGoogle Scholar
  137. 137.
    Nover AB, Lee SL, Georgescu MS et al (2015) Porous titanium bases for osteochondral tissue engineering. Acta Biomater 27:286–293. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Marta Ondrésik
    • 1
    • 2
    Email author
  • J. Miguel Oliveira
    • 1
    • 2
    • 3
  • Rui L. Reis
    • 1
    • 2
    • 3
  1. 1.3B’s Research Group – Biomaterials, Biodegradables and BiomimeticsUniversity of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineBarco, GuimarãesPortugal
  2. 2.ICVS/3B’s – PT Government Associate LaboratoryBraga/GuimarãesPortugal
  3. 3.The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of MinhoBarco, GuimarãesPortugal

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