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Cartilage pp 169-187 | Cite as

Tissue Engineering Strategies for Cartilage Repair

  • Holger JahrEmail author
Chapter

Abstract

Cartilage repair addresses several facets of the diversity in our present approaches to regenerate articulating surfaces. The following chapter now summarizes several promising options to engineer articular cartilage-like constructs, ranging from applying biological factors and/or mechanical, magnetic, or even electrical stimuli. The paradigm of cartilage tissue engineering classically comprises three pillars: cells, scaffolds, and signals. As cell sources for cartilage repair are addressed by other chapters in this volume, the next pages will focus on the two remaining pillars: first, due to their importance for the subsequent tissue engineering path, scaffold-free and scaffold-based applications are distinguished. Although most classical techniques in the field are scaffold based, relative more attention is now paid to emerging scaffold-free methods as articular cartilage repair constructs. Only proper tissue organization will permit long-term functional durability, and mimicking tissue growth without artificial support structures holds a lot of potential. While the extracellular matrix is an integral aspect of the tissue properties, it also impedes the integration of the repair construct into the surrounding host tissue. Several approaches to tackle this dilemma are depicted. The importance to develop bioreactors is also emphasized as they are inevitable for the reproducible application of sophisticated mechanobiological stimulation regimes. In this context, the contribution of selected growth factors is described. Towards the end of the present chapter, the importance of integrating multiple of these parameters into multimodal concepts for achieving phenotypic stability of the engineered cartilage-like constructs is addressed.

Keywords

Tissue Engineering Articular Cartilage Cartilage Repair Cartilage Tissue Engineering Native Cartilage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Funding from the START-Program (Grant No. 691513) of the Faculty of Medicine, RWTH Aachen, the Umbrella Research Cooperation (Grant No. 700116), and the D-Board Consortium, which has received funding from the European Union’s Seventh Framework Programme for Research, Technological Development, and Demonstration under Grant Agreement No. 305815, is acknowledged.

References

  1. Amin AK, Huntley JS, Bush PG, Simpson AH, Hall AC (2008) Osmolarity influences chondrocyte death in wounded articular cartilage. J Bone Joint Surg Am 90(7):1531–1542. doi: 10.2106/JBJS.G.00857 PubMedCrossRefGoogle Scholar
  2. Asanbaeva A, Masuda K, Thonar EJ, Klisch SM, Sah RL (2007) Mechanisms of cartilage growth: modulation of balance between proteoglycan and collagen in vitro using chondroitinase ABC. Arthritis Rheum 56(1):188–198. doi: 10.1002/art.22298 PubMedCrossRefGoogle Scholar
  3. Balint R, Cassidy NJ, Cartmell SH (2013) Electrical stimulation: a novel tool for tissue engineering. Tissue Eng Part B Rev 19(1):48–57. doi: 10.1089/ten.TEB.2012.0183 PubMedCrossRefGoogle Scholar
  4. Barrett-Jolley R, Lewis R, Fallman R, Mobasheri A (2010) The emerging chondrocyte channelome. Front Physiol 1:135. doi: 10.3389/fphys.2010.00135 PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bastiaansen-Jenniskens YM, Koevoet W, Feijt C, Bos PK, Verhaar JA, Van Osch GJ, DeGroot J (2009) Proteoglycan production is required in initial stages of new cartilage matrix formation but inhibits integrative cartilage repair. J Tissue Eng Regen Med 3(2):117–123. doi: 10.1002/term.147 PubMedCrossRefGoogle Scholar
  6. Bhumiratana S, Eton RE, Oungoulian SR, Wan LQ, Ateshian GA, Vunjak-Novakovic G (2014) Large, stratified, and mechanically functional human cartilage grown in vitro by mesenchymal condensation. Proc Natl Acad Sci U S A 111(19):6940–6945. doi: 10.1073/pnas.1324050111 PubMedPubMedCentralCrossRefGoogle Scholar
  7. Brady MA, Waldman SD, Ethier CR (2015a) The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response. Tissue Eng Part B Rev 21(1):1–19. doi: 10.1089/ten.TEB.2013.0757 PubMedCrossRefGoogle Scholar
  8. Brady MA, Waldman SD, Ethier CR (2015b) The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction. Tissue Eng Part B Rev 21(1):20–33. doi: 10.1089/ten.TEB.2013.0760 PubMedCrossRefGoogle Scholar
  9. van de Breevaart Bravenboer J, In der Maur CD, Bos PK, Feenstra L, Verhaar JA, Weinans H, van Osch GJ (2004) Improved cartilage integration and interfacial strength after enzymatic treatment in a cartilage transplantation model. Arthritis Res Ther 6(5):R469–R476. doi: 10.1186/ar1216 PubMedPubMedCentralCrossRefGoogle Scholar
  10. Browning JA, Wilkins RJ (2004) Mechanisms contributing to intracellular pH homeostasis in an immortalised human chondrocyte cell line. Comp Biochem Physiol A Mol Integr Physiol 137(2):409–418. doi: 10.1016/j.cbpb.2003.10.020 PubMedCrossRefGoogle Scholar
  11. Camarero-Espinosa S, Rothen-Rutishauser B, Foster EJ, Weder C (2016) Articular cartilage: from formation to tissue engineering. Biomater Sci. doi: 10.1039/c6bm00068a PubMedGoogle Scholar
  12. Caron MM, Emans PJ, Cremers A, Surtel DA, Coolsen MM, van Rhijn LW, Welting TJ (2013a) Hypertrophic differentiation during chondrogenic differentiation of progenitor cells is stimulated by BMP-2 but suppressed by BMP-7. Osteoarthritis Cartilage 21(4):604–613. doi: 10.1016/j.joca.2013.01.009 PubMedCrossRefGoogle Scholar
  13. Caron MM, van der Windt AE, Emans PJ, van Rhijn LW, Jahr H, Welting TJ (2013b) Osmolarity determines the in vitro chondrogenic differentiation capacity of progenitor cells via nuclear factor of activated T-cells 5. Bone 53(1):94–102. doi: 10.1016/j.bone.2012.11.032 PubMedCrossRefGoogle Scholar
  14. Chen AK, Reuveny S, Oh SK (2013) Application of human mesenchymal and pluripotent stem cell microcarrier cultures in cellular therapy: achievements and future direction. Biotechnol Adv 31(7):1032–1046. doi: 10.1016/j.biotechadv.2013.03.006 PubMedCrossRefGoogle Scholar
  15. Darling EM (2013) Articular cartilage, 1st edn. CRC Press, Taylor & Francis Group, Boca RatonGoogle Scholar
  16. Darling EM, Pritchett PE, Evans BA, Superfine R, Zauscher S, Guilak F (2009) Mechanical properties and gene expression of chondrocytes on micropatterned substrates following dedifferentiation in monolayer. Cell Mol Bioeng 2(3):395–404PubMedPubMedCentralCrossRefGoogle Scholar
  17. Das R, Kreukniet M, Oostra J, van Osch G, Weinans H, Jahr H (2008a) Control of oxygen tension and pH in a bioreactor for cartilage tissue engineering. Biomed Mater Eng 18(4-5):279–282PubMedGoogle Scholar
  18. Das RH, Jahr H, Verhaar JA, van der Linden JC, van Osch GJ, Weinans H (2008b) In vitro expansion affects the response of chondrocytes to mechanical stimulation. Osteoarthritis Cartilage 16(3):385–391. doi: 10.1016/j.joca.2007.07.014 PubMedCrossRefGoogle Scholar
  19. Das R, Jahr H, van Osch GJ, Farrell E (2010a) The role of hypoxia in bone marrow-derived mesenchymal stem cells: considerations for regenerative medicine approaches. Tissue Eng Part B Rev 16(2):159–168. doi: 10.1089/ten.TEB.2009.0296 PubMedCrossRefGoogle Scholar
  20. Das RH, van Osch GJ, Kreukniet M, Oostra J, Weinans H, Jahr H (2010b) Effects of individual control of pH and hypoxia in chondrocyte culture. J Orthop Res 28(4):537–545. doi: 10.1002/jor.20994 PubMedGoogle Scholar
  21. Das R, Timur UT, Edip S, Haak E, Wruck C, Weinans H, Jahr H (2015) TGF-beta2 is involved in the preservation of the chondrocyte phenotype under hypoxic conditions. Ann Anat 198:1–10. doi: 10.1016/j.aanat.2014.11.003 PubMedCrossRefGoogle Scholar
  22. DuRaine G, Neu CP, Chan SM, Komvopoulos K, June RK, Reddi AH (2009) Regulation of the friction coefficient of articular cartilage by TGF-beta1 and IL-1beta. J Orthop Res 27(2):249–256. doi: 10.1002/jor.20713 PubMedCrossRefGoogle Scholar
  23. DuRaine GD, Brown WE, Hu JC, Athanasiou KA (2015) Emergence of scaffold-free approaches for tissue engineering musculoskeletal cartilages. Ann Biomed Eng 43(3):543–554. doi: 10.1007/s10439-014-1161-y PubMedCrossRefGoogle Scholar
  24. Elder BD, Athanasiou KA (2008) Synergistic and additive effects of hydrostatic pressure and growth factors on tissue formation. PLoS One 3(6):e2341. doi: 10.1371/journal.pone.0002341 PubMedPubMedCentralCrossRefGoogle Scholar
  25. Elder BD, Athanasiou KA (2009a) Effects of temporal hydrostatic pressure on tissue-engineered bovine articular cartilage constructs. Tissue Eng Part A 15(5):1151–1158. doi: 10.1089/ten.tea.2008.0200 PubMedCrossRefGoogle Scholar
  26. Elder BD, Athanasiou KA (2009b) Systematic assessment of growth factor treatment on biochemical and biomechanical properties of engineered articular cartilage constructs. Osteoarthritis Cartilage 17(1):114–123. doi: 10.1016/j.joca.2008.05.006 PubMedCrossRefGoogle Scholar
  27. Eltawil NM, Howie SE, Simpson AH, Amin AK, Hall AC (2015) The use of hyperosmotic saline for chondroprotection: implications for orthopaedic surgery and cartilage repair. Osteoarthritis Cartilage 23 (3):469–477. doi: 10.1016/j.joca.2014.12.004. pii: S1063-4584(14)01374-0
  28. Fan JC, Waldman SD (2010) The effect of intermittent static biaxial tensile strains on tissue engineered cartilage. Ann Biomed Eng 38(4):1672–1682. doi: 10.1007/s10439-010-9917-5 PubMedCrossRefGoogle Scholar
  29. Fickert S, Gerwien P, Helmert B, Schattenberg T, Weckbach S, Kaszkin-Bettag M, Lehmann L (2012) One-year clinical and radiological results of a prospective, investigator-initiated trial examining a novel, purely autologous 3-dimensional autologous chondrocyte transplantation product in the knee. Cartilage 3(1):27–42. doi: 10.1177/1947603511417616 PubMedPubMedCentralCrossRefGoogle Scholar
  30. Freed LE, Vunjak-Novakovic G (1995) Cultivation of cell-polymer tissue constructs in simulated microgravity. Biotechnol Bioeng 46(4):306–313. doi: 10.1002/bit.260460403 PubMedCrossRefGoogle Scholar
  31. Freyria AM, Yang Y, Chajra H, Rousseau CF, Ronziere MC, Herbage D, El Haj AJ (2005) Optimization of dynamic culture conditions: effects on biosynthetic activities of chondrocytes grown in collagen sponges. Tissue Eng 11(5-6):674–684. doi: 10.1089/ten.2005.11.674 PubMedCrossRefGoogle Scholar
  32. Furukawa KS, Suenaga H, Toita K, Numata A, Tanaka J, Ushida T, Sakai Y, Tateishi T (2003) Rapid and large-scale formation of chondrocyte aggregates by rotational culture. Cell Transplant 12(5):475–479PubMedCrossRefGoogle Scholar
  33. Garvin J, Qi J, Maloney M, Banes AJ (2003) Novel system for engineering bioartificial tendons and application of mechanical load. Tissue Eng 9(5):967–979. doi: 10.1089/107632703322495619 PubMedCrossRefGoogle Scholar
  34. Gelinsky M, Bernhardt A, Milan F (2015) Bioreactors in tissue engineering: advances in stem cell culture and three-dimensional tissue constructs. Eng Life Sci 15:6670–6677. doi: 10.1002/elsc.201400216 CrossRefGoogle Scholar
  35. Gigout A, Buschmann MD, Jolicoeur M (2009) Chondrocytes cultured in stirred suspension with serum-free medium containing pluronic-68 aggregate and proliferate while maintaining their differentiated phenotype. Tissue Eng Part A 15(8):2237–2248. doi: 10.1089/ten.tea.2008.0256 PubMedCrossRefGoogle Scholar
  36. Goodwin TJ, Prewett TL, Wolf DA, Spaulding GF (1993) Reduced shear stress: a major component in the ability of mammalian tissues to form three-dimensional assemblies in simulated microgravity. J Cell Biochem 51(3):301–311. doi: 10.1002/jcb.240510309 PubMedCrossRefGoogle Scholar
  37. Hall AC, Horwitz ER, Wilkins RJ (1996) The cellular physiology of articular cartilage. Exp Physiol 81(3):535–545PubMedCrossRefGoogle Scholar
  38. Hansmann J, Groeber F, Kahlig A, Kleinhans C, Walles H (2013) Bioreactors in tissue engineering – principles, applications and commercial constraints. Biotechnol J 8(3):298–307. doi: 10.1002/biot.201200162 PubMedCrossRefGoogle Scholar
  39. Heywood HK, Knight MM, Lee DA (2010) Both superficial and deep zone articular chondrocyte subpopulations exhibit the Crabtree effect but have different basal oxygen consumption rates. J Cell Physiol 223(3):630–639. doi: 10.1002/jcp.22061 PubMedGoogle Scholar
  40. Hu YC (2014) Gene therapy for cartilage tissue engineering. In: Hu YC (ed) Gene therapy for cartilage and bone tissue engineering. Springer, Berlin, pp 55–89. doi: 10.1007/978-3-642-53923-7
  41. Huang Y, Zhang Y, Ding X, Liu S, Sun T (2015) Osmolarity influences chondrocyte repair after injury in human articular cartilage. J Orthop Surg Res 10:19. doi: 10.1186/s13018-015-0158-z PubMedPubMedCentralCrossRefGoogle Scholar
  42. Huey DJ, Hu JC, Athanasiou KA (2012) Unlike bone, cartilage regeneration remains elusive. Science 338(6109):917–921. doi: 10.1126/science.1222454 PubMedPubMedCentralCrossRefGoogle Scholar
  43. Hunziker EB, Kapfinger E (1998) Removal of proteoglycans from the surface of defects in articular cartilage transiently enhances coverage by repair cells. J Bone Joint Surg Br 80(1):144–150PubMedCrossRefGoogle Scholar
  44. Ingber DE (2006) Cellular mechanotransduction: putting all the pieces together again. FASEB J 20(7):811–827. doi: 10.1096/fj.05-5424rev PubMedCrossRefGoogle Scholar
  45. Jahr H (2015) HDACi and Nrf2: not from alpha to omega but from acetylation to OA. Arthritis Res Ther 17(1):381. doi: 10.1186/s13075-015-0885-x PubMedPubMedCentralCrossRefGoogle Scholar
  46. Jansen JH, Weyts FA, Westbroek I, Jahr H, Chiba H, Pols HA, Verhaar JA, van Leeuwen JP, Weinans H (2004) Stretch-induced phosphorylation of ERK1/2 depends on differentiation stage of osteoblasts. J Cell Biochem 93(3):542–551. doi: 10.1002/jcb.20162 PubMedCrossRefGoogle Scholar
  47. Jansen JH, Jahr H, Verhaar JA, Pols HA, Chiba H, Weinans H, van Leeuwen JP (2006) Stretch-induced modulation of matrix metalloproteinases in mineralizing osteoblasts via extracellular signal-regulated kinase-1/2. J Orthop Res 24(7):1480–1488. doi: 10.1002/jor.20186 PubMedCrossRefGoogle Scholar
  48. Jeon JE, Schrobback K, Hutmacher DW, Klein TJ (2012) Dynamic compression improves biosynthesis of human zonal chondrocytes from osteoarthritis patients. Osteoarthritis Cartilage 20(8):906–915. doi: 10.1016/j.joca.2012.04.019 PubMedCrossRefGoogle Scholar
  49. Jin G, Yang GH, Kim G (2015) Tissue engineering bioreactor systems for applying physical and electrical stimulations to cells. J Biomed Mater Res B Appl Biomater 103(4):935–948. doi: 10.1002/jbm.b.33268 PubMedCrossRefGoogle Scholar
  50. Jortikka MO, Parkkinen JJ, Inkinen RI, Karner J, Jarvelainen HT, Nelimarkka LO, Tammi MI, Lammi MJ (2000) The role of microtubules in the regulation of proteoglycan synthesis in chondrocytes under hydrostatic pressure. Arch Biochem Biophys 374(2):172–180. doi: 10.1006/abbi.1999.1543 PubMedCrossRefGoogle Scholar
  51. Jung S, Panchalingam KM, Wuerth RD, Rosenberg L, Behie LA (2012) Large-scale production of human mesenchymal stem cells for clinical applications. Biotechnol Appl Biochem 59(2):106–120. doi: 10.1002/bab.1006 PubMedCrossRefGoogle Scholar
  52. Khan IM, Gilbert SJ, Singhrao SK, Duance VC, Archer CW (2008) Cartilage integration: evaluation of the reasons for failure of integration during cartilage repair. A review. Eur Cell Mater 16:26–39PubMedCrossRefGoogle Scholar
  53. Kim SH, Kim SH, Jung Y (2015) TGF-beta3 encapsulated PLCL scaffold by a supercritical CO2-HFIP co-solvent system for cartilage tissue engineering. J Control Release 206:101–107. doi: 10.1016/j.jconrel.2015.03.026 PubMedCrossRefGoogle Scholar
  54. King JA, Miller WM (2007) Bioreactor development for stem cell expansion and controlled differentiation. Curr Opin Chem Biol 11(4):394–398. doi: 10.1016/j.cbpa.2007.05.034 PubMedPubMedCentralCrossRefGoogle Scholar
  55. Leddy HA, Awad HA, Guilak F (2004) Molecular diffusion in tissue-engineered cartilage constructs: effects of scaffold material, time, and culture conditions. J Biomed Mater Res B Appl Biomater 70(2):397–406. doi: 10.1002/jbm.b.30053 PubMedCrossRefGoogle Scholar
  56. Lee JK, Gegg CA, Hu JC, Kass PH, Athanasiou KA (2014) Promoting increased mechanical properties of tissue engineered neocartilage via the application of hyperosmolarity and 4alpha-phorbol 12,13-didecanoate (4alphaPDD). J Biomech 47(15):3712–3718. doi: 10.1016/j.jbiomech.2014.09.018 PubMedPubMedCentralCrossRefGoogle Scholar
  57. Leijten JC, Bos SD, Landman EB, Georgi N, Jahr H, Meulenbelt I, Post JN, van Blitterswijk CA, Karperien M (2013) GREM1, FRZB and DKK1 mRNA levels correlate with osteoarthritis and are regulated by osteoarthritis-associated factors. Arthritis Res Ther 15(5):R126. doi: 10.1186/ar4306 PubMedPubMedCentralCrossRefGoogle Scholar
  58. Little CJ, Bawolin NK, Chen X (2011) Mechanical properties of natural cartilage and tissue-engineered constructs. Tissue Eng Part B Rev 17(4):213–227PubMedCrossRefGoogle Scholar
  59. Lujan TJ, Wirtz KM, Bahney CS, Madey SM, Johnstone B, Bottlang M (2011) A novel bioreactor for the dynamic stimulation and mechanical evaluation of multiple tissue-engineered constructs. Tissue Eng Part C Methods 17(3):367–374. doi: 10.1089/ten.TEC.2010.0381 PubMedCrossRefGoogle Scholar
  60. MacBarb RF, Chen AL, Hu JC, Athanasiou KA (2013) Engineering functional anisotropy in fibrocartilage neotissues. Biomaterials 34(38):9980–9989. doi: 10.1016/j.biomaterials.2013.09.026 PubMedCrossRefGoogle Scholar
  61. Makris EA, MacBarb RF, Paschos NK, Hu JC, Athanasiou KA (2014a) Combined use of chondroitinase-ABC, TGF-beta1, and collagen crosslinking agent lysyl oxidase to engineer functional neotissues for fibrocartilage repair. Biomaterials 35(25):6787–6796. doi: 10.1016/j.biomaterials.2014.04.083 PubMedPubMedCentralCrossRefGoogle Scholar
  62. Makris EA, Responte DJ, Paschos NK, Hu JC, Athanasiou KA (2014b) Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking. Proc Natl Acad Sci U S A 111(45):E4832–E4841. doi: 10.1073/pnas.1414271111 PubMedPubMedCentralCrossRefGoogle Scholar
  63. Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA (2015) Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol 11(1):21–34. doi: 10.1038/nrrheum.2014.157 PubMedCrossRefGoogle Scholar
  64. Malda J, van Blitterswijk CA, van Geffen M, Martens DE, Tramper J, Riesle J (2004) Low oxygen tension stimulates the redifferentiation of dedifferentiated adult human nasal chondrocytes. Osteoarthritis Cartilage 12(4):306–313. doi: 10.1016/j.joca.2003.12.001 PubMedCrossRefGoogle Scholar
  65. Marlovits S, Tichy B, Truppe M, Gruber D, Schlegel W (2003a) Collagen expression in tissue engineered cartilage of aged human articular chondrocytes in a rotating bioreactor. Int J Artif Organs 26(4):319–330PubMedGoogle Scholar
  66. Marlovits S, Tichy B, Truppe M, Gruber D, Vecsei V (2003b) Chondrogenesis of aged human articular cartilage in a scaffold-free bioreactor. Tissue Eng 9(6):1215–1226. doi: 10.1089/10763270360728125 PubMedCrossRefGoogle Scholar
  67. Martin I, Wendt D, Heberer M (2004) The role of bioreactors in tissue engineering. Trends Biotechnol 22(2):80–86. doi: 10.1016/j.tibtech.2003.12.001 PubMedCrossRefGoogle Scholar
  68. Mauck RL, Nicoll SB, Seyhan SL, Ateshian GA, Hung CT (2003) Synergistic action of growth factors and dynamic loading for articular cartilage tissue engineering. Tissue Eng 9(4):597–611. doi: 10.1089/107632703768247304 PubMedCrossRefGoogle Scholar
  69. McGowan KB, Sah RL (2005) Treatment of cartilage with beta-aminopropionitrile accelerates subsequent collagen maturation and modulates integrative repair. J Orthop Res 23(3):594–601. doi: 10.1016/j.orthres.2004.02.015 PubMedCrossRefGoogle Scholar
  70. Miyanishi K, Trindade MC, Lindsey DP, Beaupre GS, Carter DR, Goodman SB, Schurman DJ, Smith RL (2006) Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro. Tissue Eng 12(6):1419–1428. doi: 10.1089/ten.2006.12.1419 PubMedCrossRefGoogle Scholar
  71. Moraes C, Chen JH, Sun Y, Simmons CA (2010) Microfabricated arrays for high-throughput screening of cellular response to cyclic substrate deformation. Lab Chip 10(2):227–234. doi: 10.1039/b914460a PubMedCrossRefGoogle Scholar
  72. Mow VC, Wang CC, Hung CT (1999) The extracellular matrix, interstitial fluid and ions as a mechanical signal transducer in articular cartilage. Osteoarthritis Cartilage 7(1):41–58PubMedCrossRefGoogle Scholar
  73. Murphy CL, Sambanis A (2001) Effect of oxygen tension and alginate encapsulation on restoration of the differentiated phenotype of passaged chondrocytes. Tissue Eng 7(6):791–803. doi: 10.1089/107632701753337735 PubMedCrossRefGoogle Scholar
  74. Natoli RM, Responte DJ, Lu BY, Athanasiou KA (2009a) Effects of multiple chondroitinase ABC applications on tissue engineered articular cartilage. J Orthop Res 27(7):949–956. doi: 10.1002/jor.20821 PubMedPubMedCentralCrossRefGoogle Scholar
  75. Natoli RM, Revell CM, Athanasiou KA (2009b) Chondroitinase ABC treatment results in greater tensile properties of self-assembled tissue-engineered articular cartilage. Tissue Eng Part A 15(10):3119–3128. doi: 10.1089/ten.TEA.2008.0478 PubMedPubMedCentralCrossRefGoogle Scholar
  76. Nebelung S, Brill N, Muller F, Tingart M, Pufe T, Merhof D, Schmitt R, Jahr H, Truhn D (2016) Towards optical coherence tomography-based elastographic evaluation of human cartilage. J Mech Behav Biomed Mater 56:106–119. doi: 10.1016/j.jmbbm.2015.11.025 PubMedCrossRefGoogle Scholar
  77. Obradovic B, Martin I, Padera RF, Treppo S, Freed LE, Vunjak-Novakovic G (2001) Integration of engineered cartilage. J Orthop Res 19(6):1089–1097. doi: 10.1016/S0736-0266(01)00030-4 PubMedCrossRefGoogle Scholar
  78. O’Connell GD, Nims RJ, Green J, Cigan AD, Ateshian GA, Hung CT (2014) Time and dose-dependent effects of chondroitinase ABC on growth of engineered cartilage. Eur Cell Mater 27:312–320PubMedPubMedCentralCrossRefGoogle Scholar
  79. Ofek G, Revell CM, Hu JC, Allison DD, Grande-Allen KJ, Athanasiou KA (2008) Matrix development in self-assembly of articular cartilage. PLoS One 3(7):e2795. doi: 10.1371/journal.pone.0002795 PubMedPubMedCentralCrossRefGoogle Scholar
  80. Pazzano D, Mercier KA, Moran JM, Fong SS, DiBiasio DD, Rulfs JX, Kohles SS, Bonassar LJ (2000) Comparison of chondrogensis in static and perfused bioreactor culture. Biotechnol Prog 16(5):893–896. doi: 10.1021/bp000082v PubMedCrossRefGoogle Scholar
  81. Pitsillides AA, Beier F (2011) Cartilage biology in osteoarthritis--lessons from developmental biology. Nat Rev Rheumatol 7(11):654–663PubMedCrossRefGoogle Scholar
  82. Portner R, Goepfert C, Wiegandt K, Janssen R, Ilinich E, Paetzold H, Eisenbarth E, Morlock M (2009) Technical strategies to improve tissue engineering of cartilage-carrier-constructs. Adv Biochem Eng Biotechnol 112:145–181. doi: 10.1007/978-3-540-69357-4_7 PubMedGoogle Scholar
  83. Raghunath J, Rollo J, Sales KM, Butler PE, Seifalian AM (2007) Biomaterials and scaffold design: key to tissue-engineering cartilage. Biotechnol Appl Biochem 46(Pt 2):73–84. doi: 10.1042/BA20060134 PubMedGoogle Scholar
  84. Rehfeldt F, Engler AJ, Eckhardt A, Ahmed F, Discher DE (2007) Cell responses to the mechanochemical microenvironment--implications for regenerative medicine and drug delivery. Adv Drug Deliv Rev 59(13):1329–1339. doi: 10.1016/j.addr.2007.08.007 PubMedPubMedCentralCrossRefGoogle Scholar
  85. Responte DJ, Arzi B, Natoli RM, Hu JC, Athanasiou KA (2012) Mechanisms underlying the synergistic enhancement of self-assembled neocartilage treated with chondroitinase-ABC and TGF-beta1. Biomaterials 33(11):3187–3194. doi: 10.1016/j.biomaterials.2012.01.028 PubMedPubMedCentralCrossRefGoogle Scholar
  86. Rice MA, Homier PM, Waters KR, Anseth KS (2008) Effects of directed gel degradation and collagenase digestion on the integration of neocartilage produced by chondrocytes encapsulated in hydrogel carriers. J Tissue Eng Regen Med 2(7):418–429. doi: 10.1002/term.113 PubMedCrossRefGoogle Scholar
  87. Saini S, Wick TM (2003) Concentric cylinder bioreactor for production of tissue engineered cartilage: effect of seeding density and hydrodynamic loading on construct development. Biotechnol Prog 19(2):510–521. doi: 10.1021/bp0256519 PubMedCrossRefGoogle Scholar
  88. Shahin K, Doran PM (2015) Shear and compression bioreactor for cartilage synthesis. Methods Mol Biol 1340:221–233. doi: 10.1007/978-1-4939-2938-2_16 PubMedCrossRefGoogle Scholar
  89. Simpkin VL, Murray DH, Hall AP, Hall AC (2007) Bicarbonate-dependent pH(i) regulation by chondrocytes within the superficial zone of bovine articular cartilage. J Cell Physiol 212(3):600–609. doi: 10.1002/jcp.21054 PubMedCrossRefGoogle Scholar
  90. Stevens MM, Marini RP, Schaefer D, Aronson J, Langer R, Shastri VP (2005) In vivo engineering of organs: the bone bioreactor. Proc Natl Acad Sci U S A 102(32):11450–11455. doi: 10.1073/pnas.0504705102 PubMedPubMedCentralCrossRefGoogle Scholar
  91. Stoddart MJ, Ettinger L, Hauselmann HJ (2006) Enhanced matrix synthesis in de novo, scaffold free cartilage-like tissue subjected to compression and shear. Biotechnol Bioeng 95(6):1043–1051. doi: 10.1002/bit.21052 PubMedCrossRefGoogle Scholar
  92. Tew SR, Peffers MJ, McKay TR, Lowe ET, Khan WS, Hardingham TE, Clegg PD (2009) Hyperosmolarity regulates SOX9 mRNA posttranscriptionally in human articular chondrocytes. Am J Physiol Cell Physiol 297(4):C898–C906PubMedPubMedCentralCrossRefGoogle Scholar
  93. Urban JP (1994) The chondrocyte: a cell under pressure. Br J Rheumatol 33(10):901–908PubMedCrossRefGoogle Scholar
  94. Vinardell T, Sheehy EJ, Buckley CT, Kelly DJ (2012) A comparison of the functionality and in vivo phenotypic stability of cartilaginous tissues engineered from different stem cell sources. Tissue Eng Part A 18(11-12):1161–1170. doi: 10.1089/ten.TEA.2011.0544 PubMedPubMedCentralCrossRefGoogle Scholar
  95. Wang YK, Chen CS (2013) Cell adhesion and mechanical stimulation in the regulation of mesenchymal stem cell differentiation. J Cell Mol Med 17(7):823–832. doi: 10.1111/jcmm.12061 PubMedPubMedCentralCrossRefGoogle Scholar
  96. Wang N, Tytell JD, Ingber DE (2009) Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 10(1):75–82. doi: 10.1038/nrm2594 PubMedCrossRefGoogle Scholar
  97. Wang N, Grad S, Stoddart MJ, Niemeyer P, Sudkamp NP, Pestka J, Alini M, Chen J, Salzmann GM (2013) Bioreactor-induced chondrocyte maturation is dependent on cell passage and onset of loading. Cartilage 4(2):165–176. doi: 10.1177/1947603512471345 PubMedPubMedCentralCrossRefGoogle Scholar
  98. Wang N, Grad S, Stoddart MJ, Niemeyer P, Reising K, Schmal H, Sudkamp NP, Alini M, Salzmann GM (2014) Particulate cartilage under bioreactor-induced compression and shear. Int Orthop 38(5):1105–1111. doi: 10.1007/s00264-013-2194-9 PubMedCrossRefGoogle Scholar
  99. Wilkins RJ, Browning JA, Urban JP (2000) Chondrocyte regulation by mechanical load. Biorheology 37(1-2):67–74PubMedGoogle Scholar
  100. van der Windt AE, Haak E, Das RH, Kops N, Welting TJ, Caron MM, van Til NP, Verhaar JA, Weinans H, Jahr H (2010a) Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro. Arthritis Res Ther 12(3):R100. doi: 10.1186/ar3031 PubMedPubMedCentralCrossRefGoogle Scholar
  101. van der Windt AE, Jahr H, Farrell E, Verhaar JA, Weinans H, van Osch GJ (2010b) Calcineurin inhibitors promote chondrogenic marker expression of dedifferentiated human adult chondrocytes via stimulation of endogenous TGFbeta1 production. Tissue Eng Part A 16(1):1–10PubMedCrossRefGoogle Scholar
  102. van der Windt AE, Haak E, Kops N, Verhaar JA, Weinans H, Jahr H (2012) Inhibiting calcineurin activity under physiologic tonicity elevates anabolic but suppresses catabolic chondrocyte markers. Arthritis Rheum 64(6):1929–1939. doi: 10.1002/art.34369 PubMedCrossRefGoogle Scholar
  103. von der Mark K, Kirsch T, Nerlich A, Kuss A, Weseloh G, Gluckert K, Stoss H (1992) Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. Arthritis Rheum 35(7):806–811PubMedCrossRefGoogle Scholar
  104. Wong M, Carter DR (2003) Articular cartilage functional histomorphology and mechanobiology: a research perspective. Bone 33(1):1–13PubMedCrossRefGoogle Scholar
  105. Xu X, Urban JP, Tirlapur UK, Cui Z (2010) Osmolarity effects on bovine articular chondrocytes during three-dimensional culture in alginate beads. Osteoarthritis Cartilage 18(3):433–439. doi: 10.1016/j.joca.2009.10.003 PubMedCrossRefGoogle Scholar
  106. Zeng C, Li H, Yang T, Deng ZH, Yang Y, Zhang Y, Lei GH (2015) Electrical stimulation for pain relief in knee osteoarthritis: systematic review and network meta-analysis. Osteoarthritis Cartilage 23(2):189–202. doi: 10.1016/j.joca.2014.11.014 PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.RWTH University Hospital AachenDepartment of Orthopaedic SurgeryAachenGermany

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