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Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering

  • Ivana Gadjanski
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1058)

Abstract

In order to engineer biomimetic osteochondral (OC) construct, it is necessary to address both the cartilage and bone phase of the construct, as well as the interface between them, in effect mimicking the developmental processes when generating hierarchical scaffolds that show gradual changes of physical and mechanical properties, ideally complemented with the biochemical gradients. There are several components whose characteristics need to be taken into account in such biomimetic approach, including cells, scaffolds, bioreactors as well as various developmental processes such as mesenchymal condensation and vascularization, that need to be stimulated through the use of growth factors, mechanical stimulation, purinergic signaling, low oxygen conditioning, and immunomodulation. This chapter gives overview of these biomimetic OC system components, including the OC interface, as well as various methods of fabrication utilized in OC biomimetic tissue engineering (TE) of gradient scaffolds. Special attention is given to addressing the issue of achieving clinical size, anatomically shaped constructs. Besides such neotissue engineering for potential clinical use, other applications of biomimetic OC TE including formation of the OC tissues to be used as high-fidelity disease/healing models and as in vitro models for drug toxicity/efficacy evaluation are covered.

Highlights

  • Biomimetic OC TE uses “smart” scaffolds able to locally regulate cell phenotypes and dual-flow bioreactors for two sets of conditions for cartilage/bone

  • Protocols for hierarchical OC grafts engineering should entail mesenchymal condensation for cartilage and vascular component for bone

  • Immunomodulation, low oxygen tension, purinergic signaling, time dependence of stimuli application are important aspects to consider in biomimetic OC TE

Keywords

Hierarchical scaffold Bioreactor Osteochondral Cartilage, Bone 

Notes

Competing interests

The author participates in a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement 664387.

Grant information

This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Projects OI174028 and III41007).

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

  1. 1.
    Gadjanski I, Vunjak-Novakovic G (2015) Challenges in engineering osteochondral tissue grafts with hierarchical structures. Expert Opin Biol Ther 15:1–17.  https://doi.org/10.1517/14712598.2015.1070825 CrossRefGoogle Scholar
  2. 2.
    Vanderburgh J, Sterling JA, Guelcher SA (2017) 3D printing of tissue engineered constructs for in vitro modeling of disease progression and drug screening. Ann Biomed Eng 45(1):164–179CrossRefGoogle Scholar
  3. 3.
    Martin I, Miot S, Barbero A, Jakob M, Wendt D (2007) Osteochondral tissue engineering. J Biomech 40(4):750–765.  https://doi.org/10.1016/j.jbiomech.2006.03.008 CrossRefPubMedGoogle Scholar
  4. 4.
    Di Luca A, Van Blitterswijk C, Moroni L (2015) The osteochondral interface as a gradient tissue: from development to the fabrication of gradient scaffolds for regenerative medicine. Birth Defects Res C Embryo Today 105(1):34–52.  https://doi.org/10.1002/bdrc.21092 CrossRefPubMedGoogle Scholar
  5. 5.
    Yan L, Oliveira JM, Oliveira AL, Reis RL (2015) Current concepts and challenges in osteochondral tissue engineering and regenerative medicine. ACS Biomater Sci EngineCrossRefGoogle Scholar
  6. 6.
    Oliveira JM, Reis RL (2016) Regenerative strategies for the treatment of knee joint disabilities. Springer, New YorkGoogle Scholar
  7. 7.
    Perdisa F, Sessa A, Filardo G, Marcacci M, Kon E (2017) Cell-free scaffolds for the treatment of chondral and osteochondral lesions. In: Gobbi A, Espregueira-Mendes J, Lane JG, Karahan M (eds) Bio-orthopaedics: a new approach. Springer, Berlin, pp 139–149.  https://doi.org/10.1007/978-3-662-54181-4_11 CrossRefGoogle Scholar
  8. 8.
    Yousefi AM, Hoque ME, Prasad RG, Uth N (2014) Current strategies in multiphasic scaffold design for osteochondral tissue engineering: a review. J Biomed Mater Res A 103:2460.  https://doi.org/10.1002/jbm.a.35356 CrossRefPubMedGoogle Scholar
  9. 9.
    von der Mark K, Gauss V, von der Mark H, Müller P (1977) Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture. Nature 267(5611):531–532CrossRefGoogle Scholar
  10. 10.
    Schnabel M, Marlovits S, Eckhoff G, Fichtel I, Gotzen L, Vecsei V, Schlegel J (2002) Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. Osteoarthritis Res Soc 10(1):62–70.  https://doi.org/10.1053/joca.2001.0482 CrossRefGoogle Scholar
  11. 11.
    Lau TT, Peck Y, Huang W, Wang D-A (2014) Optimization of chondrocyte isolation and phenotype characterization for cartilage tissue engineering. Tissue Eng Part C Methods 21(2):105–111CrossRefGoogle Scholar
  12. 12.
    Yonenaga K, Nishizawa S, Fujihara Y, Asawa Y, Sanshiro K, Nagata S, Takato T, Hoshi K (2010) The optimal conditions of chondrocyte isolation and its seeding in the preparation for cartilage tissue engineering. Tissue Eng Part C Methods 16(6):1461–1469CrossRefGoogle Scholar
  13. 13.
    Zhou M, Yuan X, Yin H, Gough JE (2015) Restoration of chondrocytic phenotype on a two-dimensional micropatterned surface. Biointerphases 10(1):011003.  https://doi.org/10.1116/1.4913565 CrossRefPubMedGoogle Scholar
  14. 14.
    Tan AR, Hung CT (2017) Concise review: mesenchymal stem cells for functional cartilage tissue engineering: taking cues from chondrocyte-based constructs. Stem Cells Transl Med 6(4):1295–1303.  https://doi.org/10.1002/sctm.16-0271 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Erickson IE, Huang AH, Chung C, Li RT, Burdick JA, Mauck RL (2009) Differential maturation and structure-function relationships in mesenchymal stem cell- and chondrocyte-seeded hydrogels. Tissue Eng A 15(5):1041–1052.  https://doi.org/10.1089/ten.tea.2008.0099 CrossRefGoogle Scholar
  16. 16.
    Rodrigues MT, Gomes ME, Reis RL (2011) Current strategies for osteochondral regeneration: from stem cells to pre-clinical approaches. Curr Opin Biotechnol 22(5):726–733.  https://doi.org/10.1016/j.copbio.2011.04.006 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Rodriguez-Fontan F, Piuzzi NS, Chahla J, Payne KA, LaPrade RF, Muschler GF, Pascual-Garrido C (2017) Stem and progenitor cells for cartilage repair: source, safety, evidence, and efficacy. Oper Tech Sports Med 25(1):25–33CrossRefGoogle Scholar
  18. 18.
    Vonk LA, De Windt TS, Slaper-Cortenbach IC, Saris DB (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(1):94CrossRefGoogle Scholar
  19. 19.
    Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. Int Soc Cell Ther 8(4):315–317Google Scholar
  20. 20.
    Castro-Malaspina H, Ebell W, Wang S (1984) Human bone marrow fibroblast colony-forming units (CFU-F). Prog Clin Biol Res 154:209–236PubMedGoogle Scholar
  21. 21.
    Ivanovic Z, Vlaski-Lafarge M (2015) Anaerobiosis and Stemness. Academic PressGoogle Scholar
  22. 22.
    Friedenstein A, Chailakhjan R, Lalykina K (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Prolif 3(4):393–403CrossRefGoogle Scholar
  23. 23.
    Muraglia A, Cancedda R, Quarto R (2000) Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J Cell Sci 113(7):1161–1166PubMedGoogle Scholar
  24. 24.
    Bernhard JC, Vunjak-Novakovic G (2016) Should we use cells, biomaterials, or tissue engineering for cartilage regeneration? Stem Cell Res Ther 7(1):56.  https://doi.org/10.1186/s13287-016-0314-3 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Wakitani S, Nawata M, Tensho K, Okabe T, Machida H, Ohgushi H (2007) Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med 1(1):74–79.  https://doi.org/10.1002/term.8 CrossRefPubMedGoogle Scholar
  26. 26.
    Huey DJ, Hu JC, Athanasiou KA (2012) Unlike bone, cartilage regeneration remains elusive. Science 338(6109):917–921.  https://doi.org/10.1126/science.1222454 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Caplan AI (2017) Mesenchymal stem cells: time to change the name! Stem Cells Transl Med 6(6):1445–1451CrossRefGoogle Scholar
  28. 28.
    Ng J, Spiller K, Bernhard J, Vunjak-Novakovic G (2017) Biomimetic approaches for bone tissue engineering. Tissue Eng Pt B: RevCrossRefGoogle Scholar
  29. 29.
    Friedenstein A, Chailakhyan R, Gerasimov U (1987) Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Prolif 20(3):263–272CrossRefGoogle Scholar
  30. 30.
    Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7(2):211–228.  https://doi.org/10.1089/107632701300062859 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Frohlich M, Grayson WL, Marolt D, Gimble JM, Kregar-Velikonja N, Vunjak-Novakovic G (2010) Bone grafts engineered from human adipose-derived stem cells in perfusion bioreactor culture. Tissue Eng A 16(1):179–189.  https://doi.org/10.1089/ten.TEA.2009.0164 CrossRefGoogle Scholar
  32. 32.
    Correia C, Bhumiratana S, Yan L-P, Oliveira AL, Gimble JM, Rockwood D, Kaplan DL, Sousa RA, Reis RL, Vunjak-Novakovic G (2012) Development of silk-based scaffolds for tissue engineering of bone from human adipose-derived stem cells. Acta Biomater 8(7):2483–2492CrossRefGoogle Scholar
  33. 33.
    Voegele TJ, Voegele-Kadletz M, Esposito V, Macfelda K, Oberndorfer U, Vecsei V, Schabus R (2000) The effect of different isolation techniques on human osteoblast-like cell growth. Anticancer Res 20(5B):3575–3581PubMedGoogle Scholar
  34. 34.
    Jonsson KB, Frost A, Nilsson O, Ljunghall S, Ljunggren O (1999) Three isolation techniques for primary culture of human osteoblast-like cells: a comparison. Acta Orthop Scand 70(4):365–373CrossRefGoogle Scholar
  35. 35.
    Hutmacher DW, Sittinger M (2003) Periosteal cells in bone tissue engineering. Tissue Eng 9(Suppl 1):S45–S64.  https://doi.org/10.1089/10763270360696978 CrossRefPubMedGoogle Scholar
  36. 36.
    Puwanun S, Smith RMD, Colley HE, Yates JM, MacNeil S, Reilly GC (2017) A simple rocker-induced mechanical stimulus upregulates mineralization by human osteoprogenitor cells in fibrous scaffolds. J Tiss Eng Regen MedCrossRefGoogle Scholar
  37. 37.
    De Bari C, Dell'Accio F, Vanlauwe J, Eyckmans J, Khan IM, Archer CW, Jones EA, McGonagle D, Mitsiadis TA, Pitzalis C, Luyten FP (2006) Mesenchymal multipotency of adult human periosteal cells demonstrated by single-cell lineage analysis. Arthritis Rheum 54(4):1209–1221.  https://doi.org/10.1002/art.21753 CrossRefPubMedGoogle Scholar
  38. 38.
    Ko JY, Park S, Im GI (2014) Osteogenesis from human induced pluripotent stem cells: an in vitro and in vivo comparison with mesenchymal stem cells. Stem Cells Dev 23(15):1788–1797.  https://doi.org/10.1089/scd.2014.0043 CrossRefPubMedGoogle Scholar
  39. 39.
    Bigdeli N, Karlsson C, Strehl R, Concaro S, Hyllner J, Lindahl A (2009) Coculture of human embryonic stem cells and human articular chondrocytes results in significantly altered phenotype and improved chondrogenic differentiation. Stem Cells 27(8):1812–1821.  https://doi.org/10.1002/stem.114 CrossRefPubMedGoogle Scholar
  40. 40.
    Lee TJ, Jang J, Kang S, Bhang SH, Jeong GJ, Shin H, Kim DW, Kim BS (2014) Mesenchymal stem cell-conditioned medium enhances osteogenic and chondrogenic differentiation of human embryonic stem cells and human induced pluripotent stem cells by mesodermal lineage induction. Tissue Eng A 20(7–8):1306–1313.  https://doi.org/10.1089/ten.TEA.2013.0265 CrossRefGoogle Scholar
  41. 41.
    Marolt D, Campos IM, Bhumiratana S, Koren A, Petridis P, Zhang G, Spitalnik PF, Grayson WL, Vunjak-Novakovic G (2012) Engineering bone tissue from human embryonic stem cells. Proc Natl Acad Sci U S A 109(22):8705–8709.  https://doi.org/10.1073/pnas.1201830109 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Cheng A, Hardingham TE, Kimber SJ (2014) Generating cartilage repair from pluripotent stem cells. Tissue Eng Part B Rev 20(4):257–266.  https://doi.org/10.1089/ten.TEB.2012.0757 CrossRefPubMedGoogle Scholar
  43. 43.
    Oldershaw RA, Baxter MA, Lowe ET, Bates N, Grady LM, Soncin F, Brison DR, Hardingham TE, Kimber SJ (2010) Directed differentiation of human embryonic stem cells toward chondrocytes. Nat Biotechnol 28(11):1187–1194.  https://doi.org/10.1038/nbt.1683 CrossRefPubMedGoogle Scholar
  44. 44.
    Chari S, Mao S (2016) Timeline: iPSCs--the first decade. Cell Stem Cell 18(2):294.  https://doi.org/10.1016/j.stem.2016.01.005 CrossRefPubMedGoogle Scholar
  45. 45.
    Yoshihara M, Hayashizaki Y, Murakawa Y (2017) Genomic instability of iPSCs: challenges towards their clinical applications. Stem Cell Rev Rep 13(1):7–16CrossRefGoogle Scholar
  46. 46.
    Nejadnik H, Diecke S, Lenkov OD, Chapelin F, Donig J, Tong X, Derugin N, Chan RC, Gaur A, Yang F, Wu JC, Daldrup-Link HE (2015) Improved approach for Chondrogenic differentiation of human induced pluripotent stem cells. Stem Cell Rev 11:242.  https://doi.org/10.1007/s12015-014-9581-5 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Suchorska WM, Augustyniak E, Richter M, Trzeciak T (2017) Comparison of four protocols to generate chondrocyte-like cells from human induced pluripotent stem cells (hiPSCs). Stem Cell Rev Rep 13(2):299–308CrossRefGoogle Scholar
  48. 48.
    de Peppo GM, Vunjak-Novakovic G, Marolt D (2014) Cultivation of human bone-like tissue from pluripotent stem cell-derived osteogenic progenitors in perfusion bioreactors. Methods Mol Biol 1202:173–184.  https://doi.org/10.1007/7651_2013_52 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Wu Q, Yang B, Hu K, Cao C, Man Y, Wang P (2017) Deriving osteogenic cells from induced pluripotent stem cells for bone tissue engineering. Tissue Eng Part B Rev 23(1):1–8CrossRefGoogle Scholar
  50. 50.
    Outani H, Okada M, Yamashita A, Nakagawa K, Yoshikawa H, Tsumaki N (2013) Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors. PLoS One 8(10):e77365.  https://doi.org/10.1371/journal.pone.0077365 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Tsumaki N, Okada M, Yamashita A (2015) iPS cell technologies and cartilage regeneration. Bone 70:48–54.  https://doi.org/10.1016/j.bone.2014.07.011 CrossRefPubMedGoogle Scholar
  52. 52.
    Gadjanski I, Spiller K, Vunjak-Novakovic G (2012) Time-dependent processes in stem cell-based tissue engineering of articular cartilage. Stem Cell Rev 8(3):863–881.  https://doi.org/10.1007/s12015-011-9328-5 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Shum L, Nuckolls G (2002) The life cycle of chondrocytes in the developing skeleton. Arthritis Res 4(2):94–106.  https://doi.org/10.1186/ar396 CrossRefPubMedGoogle Scholar
  54. 54.
    Tuli R, Tuli S, Nandi S, Huang X, Manner PA, Hozack WJ, Danielson KG, Hall DJ, Tuan RS (2003) Transforming growth factor-beta-mediated chondrogenesis of human mesenchymal progenitor cells involves N-cadherin and mitogen-activated protein kinase and Wnt signaling cross-talk. J Biol Chem 278(42):41227–41236.  https://doi.org/10.1074/jbc.M305312200 CrossRefPubMedGoogle Scholar
  55. 55.
    Grafe I, Alexander S, Peterson JR, Snider TN, Levi B, Lee B, Mishina Y (2017) TGF-β family signaling in mesenchymal differentiation. Cold Spring Harbor Perspect Biol. a022202Google Scholar
  56. 56.
    Hu JC, Athanasiou KA (2006) A self-assembling process in articular cartilage tissue engineering. Tissue Eng 12(4):969–979.  https://doi.org/10.1089/ten.2006.12.969 CrossRefPubMedGoogle Scholar
  57. 57.
    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.  https://doi.org/10.1073/pnas.1324050111 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Ng JJ, Wei Y, Zhou B, Bernhard J, Robinson S, Burapachaisri A, Guo XE, Vunjak-Novakovic G (2017) Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage. Proc Natl Acad Sci U S A 114(10):2556–2561.  https://doi.org/10.1073/pnas.1611771114 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Bhumiratana S, Vunjak-Novakovic G (2015) Engineering physiologically stiff and stratified human cartilage by fusing condensed mesenchymal stem cells. Methods 84:109.  https://doi.org/10.1016/j.ymeth.2015.03.016 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Athanasiou KA, Eswaramoorthy R, Hadidi P, Hu JC (2013) Self-organization and the self-assembling process in tissue engineering. Annu Rev Biomed Eng 15:115–136.  https://doi.org/10.1146/annurev-bioeng-071812-152423 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Spiller KL, Maher SA, Lowman AM (2011) Hydrogels for the repair of articular cartilage defects. Tissue Eng Part B Rev 17(4):281–299.  https://doi.org/10.1089/ten.TEB.2011.0077 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Yang J, Zhang YS, Yue K, Khademhosseini A (2017) Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta BiomaterialiaCrossRefGoogle Scholar
  63. 63.
    Ren K, He C, Xiao C, Li G, Chen X (2015) Injectable glycopolypeptide hydrogels as biomimetic scaffolds for cartilage tissue engineering. Biomaterials 51:238–249.  https://doi.org/10.1016/j.biomaterials.2015.02.026 CrossRefPubMedGoogle Scholar
  64. 64.
    Visser J, Melchels FP, Jeon JE, van Bussel EM, Kimpton LS, Byrne HM, Dhert WJ, Dalton PD, Hutmacher DW, Malda J (2015) Reinforcement of hydrogels using three-dimensionally printed microfibres. Nat Commun 6:6933.  https://doi.org/10.1038/ncomms7933 CrossRefPubMedGoogle Scholar
  65. 65.
    Wang C, Hou W, Guo X, Li J, Hu T, Qiu M, Liu S, Mo X, Liu X (2017) Two-phase electrospinning to incorporate growth factors loaded chitosan nanoparticles into electrospun fibrous scaffolds for bioactivity retention and cartilage regeneration. Mater Sci Eng C 79:507–515CrossRefGoogle Scholar
  66. 66.
    Zhu D, Tong X, Trinh P, Yang F (2017) Mimicking cartilage tissue zonal organization by engineering tissue-scale gradient hydrogels as 3D cell niche. Tissue Eng Part A 24:1.  https://doi.org/10.1089/ten.TEA.2016.0453 CrossRefPubMedGoogle Scholar
  67. 67.
    Camarero-Espinosa S, Cooper-White J (2017) Tailoring biomaterial scaffolds for osteochondral repair. Int J Pharm 523(2):476–489.  https://doi.org/10.1016/j.ijpharm.2016.10.035 CrossRefPubMedGoogle Scholar
  68. 68.
    Sreejalekshmi KG, Nair PD (2011) Biomimeticity in tissue engineering scaffolds through synthetic peptide modifications-altering chemistry for enhanced biological response. J Biomed Mater Res A 96(2):477–491.  https://doi.org/10.1002/jbm.a.32980 CrossRefPubMedGoogle Scholar
  69. 69.
    Bourgine PE, Gaudiello E, Pippenger B, Jaquiery C, Klein T, Pigeot S, Todorov A, Feliciano S, Banfi A, Martin I (2017) Engineered extracellular matrices as biomaterials of tunable composition and function. Adv Funct MaterCrossRefGoogle Scholar
  70. 70.
    Song JJ, Ott HC (2011) Organ engineering based on decellularized matrix scaffolds. Trends Mol Med 17(8):424–432.  https://doi.org/10.1016/j.molmed.2011.03.005 CrossRefPubMedGoogle Scholar
  71. 71.
    Grayson WL, Frohlich M, Yeager K, Bhumiratana S, Chan ME, Cannizzaro C, Wan LQ, Liu XS, Guo XE, Vunjak-Novakovic G (2010) Engineering anatomically shaped human bone grafts. Proc Natl Acad Sci U S A 107(8):3299–3304.  https://doi.org/10.1073/pnas.0905439106 CrossRefPubMedGoogle Scholar
  72. 72.
    Karageorgiou V, Kaplan D (2005) Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 26(27):5474–5491.  https://doi.org/10.1016/j.biomaterials.2005.02.002 CrossRefPubMedGoogle Scholar
  73. 73.
    Loh QL, Choong C (2013) Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size. Tissue Eng Part B Rev 19(6):485–502.  https://doi.org/10.1089/ten.TEB.2012.0437 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Hollister SJ (2005) Porous scaffold design for tissue engineering. Nat Mater 4(7):518–524.  https://doi.org/10.1038/nmat1421 CrossRefPubMedGoogle Scholar
  75. 75.
    Hendrikson WJ, van Blitterswijk CA, Rouwkema J, Moroni L (2017) The use of finite element analyses to design and fabricate three-dimensional scaffolds for skeletal tissue engineering. Front Bioeng Biotechnol 5:30.  https://doi.org/10.3389/fbioe.2017.00030 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Marrella A, Aiello M, Quarto R, Scaglione S (2016) Chemical and morphological gradient scaffolds to mimic hierarchically complex tissues: from theoretical modeling to their fabrication. Biotechnol Bioeng 113(10):2286–2297.  https://doi.org/10.1002/bit.25994 CrossRefPubMedGoogle Scholar
  77. 77.
    Rajasekharan AK, Bordes R, Sandstrom C, Ekh M, Andersson M (2017) Hierarchical and heterogeneous bioinspired composites-merging molecular self-assembly with additive manufacturing. Small 13.  https://doi.org/10.1002/smll.201700550
  78. 78.
    Bracaglia LG, Smith BT, Watson E, Arumugasaamy N, Mikos AG, Fisher JP (2017) 3D printing for the design and fabrication of polymer-based gradient scaffolds. Acta Biomater 56:3.  https://doi.org/10.1016/j.actbio.2017.03.030 CrossRefPubMedGoogle Scholar
  79. 79.
    Guo T, Lembong J, Zhang LG, Fisher JP (2017) Three-dimensional printing articular cartilage: recapitulating the complexity of native tissue. Tissue Eng Part B Rev 23(3):225–236.  https://doi.org/10.1089/ten.TEB.2016.0316 CrossRefPubMedGoogle Scholar
  80. 80.
    Hendrikson WJ, Deegan AJ, Yang Y, van Blitterswijk CA, Verdonschot N, Moroni L, Rouwkema J (2017) Influence of additive manufactured scaffold architecture on the distribution of surface strains and fluid flow shear stresses and expected osteochondral cell differentiation. Front Bioeng Biotech 5Google Scholar
  81. 81.
    Murphy SV, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32(8):773–785.  https://doi.org/10.1038/nbt.2958 CrossRefGoogle Scholar
  82. 82.
    Cui X, Breitenkamp K, Finn MG, Lotz M, D'Lima DD (2012) Direct human cartilage repair using three-dimensional bioprinting technology. Tissue Eng A 18(11–12):1304–1312.  https://doi.org/10.1089/ten.TEA.2011.0543 CrossRefGoogle Scholar
  83. 83.
    Panwar A, Tan LP (2016) Current status of bioinks for micro-extrusion-based 3D bioprinting. Molecules 21(6).  https://doi.org/10.3390/molecules21060685
  84. 84.
    Keriquel V, Oliveira H, Remy M, Ziane S, Delmond S, Rousseau B, Rey S, Catros S, Amedee J, Guillemot F, Fricain JC (2017) In situ printing of mesenchymal stromal cells, by laser-assisted bioprinting, for in vivo bone regeneration applications. Sci Rep 7(1):1778.  https://doi.org/10.1038/s41598-017-01914-x CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Hinton TJ, Jallerat Q, Palchesko RN, Park JH, Grodzicki MS, Shue H-J, Ramadan MH, Hudson AR, Feinberg AW (2015) Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels. Sci Adv 1(9):e1500758CrossRefGoogle Scholar
  86. 86.
    Mellor LF, Huebner P, Cai S, Mohiti-Asli M, Taylor MA, Spang J, Shirwaiker RA (2017) Loboa EG (2017) fabrication and evaluation of electrospun, 3D-bioplotted, and combination of electrospun/3D-bioplotted scaffolds for tissue engineering applications. Biomed Res Int 2017:1CrossRefGoogle Scholar
  87. 87.
    Alexander PG, Gottardi R, Lin H, Lozito TP, Tuan RS (2014) Three-dimensional osteogenic and chondrogenic systems to model osteochondral physiology and degenerative joint diseases. Exp Biol Med 239(9):1080–1095.  https://doi.org/10.1177/1535370214539232 CrossRefGoogle Scholar
  88. 88.
    Ikegawa S (2006) Genetic analysis of skeletal dysplasia: recent advances and perspectives in the post-genome-sequence era. J Hum Genet 51(7):581–586.  https://doi.org/10.1007/s10038-006-0401-x CrossRefPubMedGoogle Scholar
  89. 89.
    Diederichs S, Richter W (2017) Induced pluripotent stem cells and cartilage regeneration. Cartilage. Springer, In, pp 73–93Google Scholar
  90. 90.
    Brookhouser N, Raman S, Potts C, Brafman DA (2017) May I cut in? Gene editing approaches in human induced pluripotent stem cells. Cells 6(1):5CrossRefGoogle Scholar
  91. 91.
    Grskovic M, Javaherian A, Strulovici B, Daley GQ (2011) Induced pluripotent stem cells—opportunities for disease modelling and drug discovery. Nat Rev Drug Discov 10(12):915–929PubMedGoogle Scholar
  92. 92.
    Wu SM, Hochedlinger K (2011) Harnessing the potential of induced pluripotent stem cells for regenerative medicine. Nat Cell Biol 13(5):497–505CrossRefGoogle Scholar
  93. 93.
    Grayson WL, Bhumiratana S, Grace Chao PH, Hung CT, Vunjak-Novakovic G (2010) Spatial regulation of human mesenchymal stem cell differentiation in engineered osteochondral constructs: effects of pre-differentiation, soluble factors and medium perfusion. Osteoarthritis Res Soc 18(5):714–723.  https://doi.org/10.1016/j.joca.2010.01.008 CrossRefGoogle Scholar
  94. 94.
    Steinmetz NJ, Aisenbrey EA, Westbrook KK, Qi HJ, Bryant SJ (2015) Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering. Acta Biomater 21:142–153.  https://doi.org/10.1016/j.actbio.2015.04.015 CrossRefPubMedGoogle Scholar
  95. 95.
    Aisenbrey E, Bryant S (2016) Mechanical loading inhibits hypertrophy in chondrogenically differentiating hMSCs within a biomimetic hydrogel. J Mater Chem B 4(20):3562–3574CrossRefGoogle Scholar
  96. 96.
    Vunjak-Novakovic G, Meinel L, Altman G, Kaplan D (2005) Bioreactor cultivation of osteochondral grafts. Orthod Craniofac Res 8(3):209–218.  https://doi.org/10.1111/j.1601-6343.2005.00334.x CrossRefPubMedGoogle Scholar
  97. 97.
    Grayson WL, Chao PH, Marolt D, Kaplan DL, Vunjak-Novakovic G (2008) Engineering custom-designed osteochondral tissue grafts. Trends Biotechnol 26(4):181–189.  https://doi.org/10.1016/j.tibtech.2007.12.009 CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Temple JP, Yeager K, Bhumiratana S, Vunjak-Novakovic G, Grayson WL (2014) Bioreactor cultivation of anatomically shaped human bone grafts. Methods Mol Biol 1202:57–78.  https://doi.org/10.1007/7651_2013_33 CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Bhumiratana S, Bernhard J, Cimetta E, Vunjak-Novakovic G (2013) Principles of bioreactor design for tissue engineering. Prin Tiss Eng. 261–278Google Scholar
  100. 100.
    Petrenko Y, Petrenko A, Martin I, Wendt D (2017) Perfusion bioreactor-based cryopreservation of 3D human mesenchymal stromal cell tissue grafts. Cryobiology 76:150–153CrossRefGoogle Scholar
  101. 101.
    Murphy MK, Huey DJ, Hu JC, Athanasiou KA (2015) TGF-beta1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells. Stem Cells 33(3):762–773.  https://doi.org/10.1002/stem.1890 CrossRefPubMedGoogle Scholar
  102. 102.
    Fortier LA, Barker JU, Strauss EJ, McCarrel TM, Cole BJ (2011) The role of growth factors in cartilage repair. Clin Orthop Relat Res 469(10):2706–2715CrossRefGoogle Scholar
  103. 103.
    Martin I, Suetterlin R, Baschong W, Heberer M, Vunjak-Novakovic G, Freed LE (2001) Enhanced cartilage tissue engineering by sequential exposure of chondrocytes to FGF-2 during 2D expansion and BMP-2 during 3D cultivation. J Cell Biochem 83(1):121–128CrossRefGoogle Scholar
  104. 104.
    Byers BA, Mauck RL, Chiang IE, Tuan RS (2008) Transient exposure to transforming growth factor beta 3 under serum-free conditions enhances the biomechanical and biochemical maturation of tissue-engineered cartilage. Tissue Eng A 14(11):1821–1834.  https://doi.org/10.1089/ten.tea.2007.0222 CrossRefGoogle Scholar
  105. 105.
    Buxton AN, Bahney CS, Yoo JU, Johnstone B (2011) Temporal exposure to chondrogenic factors modulates human mesenchymal stem cell chondrogenesis in hydrogels. Tissue Eng A 17(3–4):371–380.  https://doi.org/10.1089/ten.TEA.2009.0839 CrossRefGoogle Scholar
  106. 106.
    Aksel H, Huang GT (2017) Combined effects of vascular endothelial growth factor and bone morphogenetic protein 2 on Odonto/osteogenic differentiation of human dental pulp stem cells in vitro. J Endod 43(6):930–935.  https://doi.org/10.1016/j.joen.2017.01.036 CrossRefPubMedGoogle Scholar
  107. 107.
    Song K, Rao NJ, Chen ML, Huang ZJ, Cao YG (2011) Enhanced bone regeneration with sequential delivery of basic fibroblast growth factor and sonic hedgehog. Injury 42(8):796–802.  https://doi.org/10.1016/j.injury.2011.02.003 CrossRefPubMedGoogle Scholar
  108. 108.
    Stegen S, van Gastel N, Carmeliet G (2015) Bringing new life to damaged bone: the importance of angiogenesis in bone repair and regeneration. Bone 70:19–27CrossRefGoogle Scholar
  109. 109.
    Correia C, Grayson WL, Park M, Hutton D, Zhou B, Guo XE, Niklason L, Sousa RA, Reis RL, Vunjak-Novakovic G (2011) In vitro model of vascularized bone: synergizing vascular development and osteogenesis. PLoS One 6(12):e28352.  https://doi.org/10.1371/journal.pone.0028352 CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Spiller KL, Anfang RR, Spiller KJ, Ng J, Nakazawa KR, Daulton JW, Vunjak-Novakovic G (2014) The role of macrophage phenotype in vascularization of tissue engineering scaffolds. Biomaterials 35(15):4477–4488.  https://doi.org/10.1016/j.biomaterials.2014.02.012 CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Qi JH, Ebrahem Q, Moore N, Murphy G, Claesson-Welsh L, Bond M, Baker A, Anand-Apte B (2003) A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med 9(4):407–415.  https://doi.org/10.1038/nm846 CrossRefPubMedGoogle Scholar
  112. 112.
    Mohammed FF, Smookler DS, Taylor SE, Fingleton B, Kassiri Z, Sanchez OH, English JL, Matrisian LM, Au B, Yeh WC, Khokha R (2004) Abnormal TNF activity in Timp3−/− mice leads to chronic hepatic inflammation and failure of liver regeneration. Nat Genet 36(9):969–977.  https://doi.org/10.1038/ng1413 CrossRefPubMedGoogle Scholar
  113. 113.
    Saunders WB, Bohnsack BL, Faske JB, Anthis NJ, Bayless KJ, Hirschi KK, Davis GE (2006) Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. J Cell Biol 175(1):179–191.  https://doi.org/10.1083/jcb.200603176 CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Luz-Crawford P, Jorgensen C, Djouad F (2017) Mesenchymal stem cells direct the immunological fate of macrophages. In: Macrophages. Springer, pp 61–72Google Scholar
  115. 115.
    Hoogduijn MJ (2017) Immunomodulation by mesenchymal stem cells: lessons from vascularized composite Allotransplantation. Transplantation 101(1):30–31CrossRefGoogle Scholar
  116. 116.
    Spiller KL, Nassiri S, Witherel CE, Anfang RR, Ng J, Nakazawa KR, Yu T, Vunjak-Novakovic G (2015) Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials 37:194–207CrossRefGoogle Scholar
  117. 117.
    Schipani E, Ryan HE, Didrickson S, Kobayashi T, Knight M, Johnson RS (2001) Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev 15(21):2865–2876.  https://doi.org/10.1101/gad.934301 CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Maes C, Carmeliet G, Schipani E (2012) Hypoxia-driven pathways in bone development, regeneration and disease. Nat Rev Rheumatol 8(6):358–366CrossRefGoogle Scholar
  119. 119.
    Schipani E, Maes C, Carmeliet G, Semenza GL (2009) Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J Bone Miner Res 24(8):1347–1353CrossRefGoogle Scholar
  120. 120.
    Wang GL, Jiang BH, Rue EA, Semenza GL (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 92(12):5510–5514CrossRefGoogle Scholar
  121. 121.
    Myllyharju J, Schipani E (2010) Extracellular matrix genes as hypoxia-inducible targets. Cell Tissue Res 339(1):19–29.  https://doi.org/10.1007/s00441-009-0841-7 CrossRefPubMedGoogle Scholar
  122. 122.
    Carreau A, Hafny-Rahbi BE, Matejuk A, Grillon C, Kieda C (2011) Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. J Cell Mol Med 15(6):1239–1253CrossRefGoogle Scholar
  123. 123.
    Gnaiger E (2003) Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology. Adv Exp Med Biol 543:39–55CrossRefGoogle Scholar
  124. 124.
    Yodmuang S, Gadjanski I, Chao PH, Vunjak-Novakovic G (2013) Transient hypoxia improves matrix properties in tissue engineered cartilage. J Orthop Res 31(4):544–553.  https://doi.org/10.1002/jor.22275 CrossRefPubMedGoogle Scholar
  125. 125.
    Henrionnet C, Liang G, Roeder E, Dossot M, Wang H, Magdalou J, Gillet P, Pinzano A (2017) Hypoxia for mesenchymal stem cell expansion and differentiation: the best way for enhancing TGFß-induced Chondrogenesis and preventing calcifications in alginate beads. Tissue Eng AGoogle Scholar
  126. 126.
    Ramage L, Nuki G, Salter DM (2009) Signalling cascades in mechanotransduction: cell-matrix interactions and mechanical loading. Scand J Med Sci Sports 19(4):457–469.  https://doi.org/10.1111/j.1600-0838.2009.00912.x CrossRefPubMedGoogle Scholar
  127. 127.
    Bougault C, Paumier A, Aubert-Foucher E, Mallein-Gerin F (2009) Investigating conversion of mechanical force into biochemical signaling in three-dimensional chondrocyte cultures. Nat Protoc 4(6):928–938.  https://doi.org/10.1038/nprot.2009.63 CrossRefPubMedGoogle Scholar
  128. 128.
    Pingguan-Murphy B, El-Azzeh M, Bader D, Knight M (2006) Cyclic compression of chondrocytes modulates a purinergic calcium signalling pathway in a strain rate-and frequency-dependent manner. J Cell Physiol 209(2):389–397CrossRefGoogle Scholar
  129. 129.
    Graff RD, Lazarowski ER, Banes AJ, Lee GM (2000) ATP release by mechanically loaded porcine chondrons in pellet culture. Arthritis Rheum 43(7):1571–1579.  https://doi.org/10.1002/1529-0131(200007)43:7<1571::AID-ANR22>3.0.CO;2-L CrossRefPubMedGoogle Scholar
  130. 130.
    Knight MM, McGlashan SR, Garcia M, Jensen CG, Poole CA (2009) Articular chondrocytes express connexin 43 hemichannels and P2 receptors - a putative mechanoreceptor complex involving the primary cilium? J Anat 214(2):275–283.  https://doi.org/10.1111/j.1469-7580.2008.01021.x CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Garcia M, Knight MM (2010) Cyclic loading opens hemichannels to release ATP as part of a chondrocyte mechanotransduction pathway. J Orthop Res 28(4):510–515.  https://doi.org/10.1002/jor.21025 CrossRefPubMedGoogle Scholar
  132. 132.
    Gonzales S, Wang C, Levene H, Cheung HS, Huang CY (2015) ATP promotes extracellular matrix biosynthesis of intervertebral disc cells. Cell Tissue Res 359(2):635–642.  https://doi.org/10.1007/s00441-014-2042-2 CrossRefPubMedGoogle Scholar
  133. 133.
    Waldman SD, Usprech J, Flynn LE, Khan AA (2010) Harnessing the purinergic receptor pathway to develop functional engineered cartilage constructs. Osteoarthritis Res Soc 18(6):864–872.  https://doi.org/10.1016/j.joca.2010.03.003 CrossRefGoogle Scholar
  134. 134.
    Gadjanski I, Yodmuang S, Spiller K, Bhumiratana S, Vunjak-Novakovic G (2013) Supplementation of exogenous adenosine 5′-triphosphate enhances mechanical properties of 3D cell-agarose constructs for cartilage tissue engineering. Tissue Eng A 19(19–20):2188–2200.  https://doi.org/10.1089/ten.TEA.2012.0352 CrossRefGoogle Scholar
  135. 135.
    Brady MA, Waldman SD, Ethier CR (2014) 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):20–33CrossRefGoogle Scholar
  136. 136.
    Steward AJ, Kelly DJ, Wagner DR (2016) Purinergic signaling regulates the transforming growth factor-β3-induced Chondrogenic response of mesenchymal stem cells to hydrostatic pressure. Tissue Eng A 22(11–12):831–839CrossRefGoogle Scholar
  137. 137.
    Gadjanski I, Filipovic N Mathematical modeling of ATP release in response to mechanical stimulation of chondrogenic cells. In: Bioinformatics and Bioengineering (BIBE), 2015 IEEE 15th International Conference on, 2015. IEEE, pp 1–5Google Scholar
  138. 138.
    Rumney RM, Wang N, Agrawal A, Gartland A (2012) Purinergic signalling in bone. Front Endocrinol 3Google Scholar
  139. 139.
    Dixon SJ, Sims SM (2000) P2 purinergic receptors on osteoblasts and osteoclasts: potential targets for drug development. Drug Dev Res 49(3):187–200CrossRefGoogle Scholar
  140. 140.
    Lazarowski ER, Boucher RC, Harden TK (2000) Constitutive release of ATP and evidence for major contribution of ecto-nucleotide pyrophosphatase and nucleoside diphosphokinase to extracellular nucleotide concentrations. J Biol Chem 275(40):31061–31068.  https://doi.org/10.1074/jbc.M003255200 CrossRefPubMedGoogle Scholar
  141. 141.
    Burnstock G, Knight GE (2017) Cell culture: complications due to mechanical release of ATP and activation of purinoceptors. Cell Tissue Res 370:1–11CrossRefGoogle Scholar
  142. 142.
    Schaefer D, Martin I, Shastri P, Padera RF, Langer R, Freed LE, Vunjak-Novakovic G (2000) In vitro generation of osteochondral composites. Biomaterials 21(24):2599–2606CrossRefGoogle Scholar
  143. 143.
    Jeon JE, Vaquette C, Theodoropoulos C, Klein TJ, Hutmacher DW (2014) Multiphasic construct studied in an ectopic osteochondral defect model. J Royal Soc Interf/Royal Soc 11(95):20140184.  https://doi.org/10.1098/rsif.2014.0184 CrossRefGoogle Scholar
  144. 144.
    Cross LM, Shah K, Palani S, Peak CW, Gaharwar AK (2017) Gradient nanocomposite hydrogels for Interface tissue engineering. Nanomedicine: Nanotechnol Biol MedGoogle Scholar
  145. 145.
    D'Amora U, D'Este M, Eglin D, Safari F, Sprecher CM, Gloria A, De Santis R, Alini M, Ambrosio L (2017) Collagen density gradient on 3D printed poly (ε-Caprolactone) scaffolds for Interface tissue engineering. J Tissue Eng Regen MedGoogle Scholar
  146. 146.
    Dormer NH, Singh M, Wang L, Berkland CJ, Detamore MS (2010) Osteochondral interface tissue engineering using macroscopic gradients of bioactive signals. Ann Biomed Eng 38(6):2167–2182.  https://doi.org/10.1007/s10439-010-0028-0 CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Perez RA, Won JE, Knowles JC, Kim HW (2013) Naturally and synthetic smart composite biomaterials for tissue regeneration. Adv Drug Deliv Rev 65(4):471–496.  https://doi.org/10.1016/j.addr.2012.03.009 CrossRefGoogle Scholar
  148. 148.
    Mohan N, Gupta V, Sridharan B, Sutherland A, Detamore MS (2014) The potential of encapsulating "raw materials" in 3D osteochondral gradient scaffolds. Biotechnol Bioeng 111(4):829–841.  https://doi.org/10.1002/bit.25145 CrossRefPubMedGoogle Scholar
  149. 149.
    Qu D, Mosher CZ, Boushell MK, Lu HH (2015) Engineering complex orthopaedic tissues via strategic biomimicry. Ann Biomed Eng 43(3):697–717.  https://doi.org/10.1007/s10439-014-1190-6 CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Ivana Gadjanski
    • 1
    • 2
  1. 1.BioSense Institute, University of Novi SadDr Zorana Djindjica, Novi SadSerbia
  2. 2.Belgrade Metropolitan UniversityBelgradeSerbia

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