Silk Fibroin-Based Hydrogels and Scaffolds for Osteochondral Repair and Regeneration

  • Viviana P. RibeiroEmail author
  • Sandra Pina
  • J. Miguel Oliveira
  • Rui L. Reis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1058)


Osteochondral lesions treatment and regeneration demands biomimetic strategies aiming physicochemical and biological properties of both bone and cartilage tissues, with long-term clinical outcomes. Hydrogels and scaffolds appeared as assertive approaches to guide the development and structure of the new osteochondral engineered tissue. Moreover, these structures alone or in combination with cells and bioactive molecules bring the mechanical support after in vitro and in vivo implantation. Moreover, multilayered structures designed with continuous interfaces furnish appropriate features of the cartilage and subchondral regions, namely microstructure, composition, and mechanical properties. Owing the potential as scaffolding materials, natural and synthetic polymers, bioceramics, and composites have been employed. Particularly, significance is attributed to the natural-based biopolymer silk fibroin from the Bombyx mori silkworm, considering its unique mechanical and biological properties. The significant studies on silk fibroin-based structures, namely hydrogels and scaffolds, towards bone, cartilage, and osteochondral tissue repair and regeneration are overviewed herein. The developed biomimetic strategies, processing methodologies, and final properties of the structures are summarized and discussed in depth.


Silk fibroin Hydrogels Scaffolds Osteochondral regeneration 



The authors thank to the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The financial support from the Portuguese Foundation for Science and Technology to Hierarchitech project (M-ERA-NET/0001/2014), for the fellowship grant (SFRH/BPD/113806/2015) and for the fund provided under the program Investigador for J. M. Oliveira (IF/00423/2012 and IF/01285/2015) are also greatly acknowledged.


  1. 1.
    Nerem RM, Sambanis A (1995) Tissue engineering: from biology to biological substitutes. Tissue Eng 1(1):3–13CrossRefGoogle Scholar
  2. 2.
    Langer R, Vacanti JP, Vacanti CA, Atala A, Freed LE, Vunjak-Novakovic G (1995) Tissue engineering: biomedical applications. Tissue Eng 1(2):151–161CrossRefGoogle Scholar
  3. 3.
    Hubbell JA (1995) Biomaterials in tissue engineering. Nat Biotechnol 13(6):565–576CrossRefGoogle Scholar
  4. 4.
    Ma PX (2008) Biomimetic materials for tissue engineering. Adv Drug Deliv Rev 60(2):184–198CrossRefGoogle Scholar
  5. 5.
    Furth ME, Atala A, Van Dyke ME (2007) Smart biomaterials design for tissue engineering and regenerative medicine. Biomaterials 28(34):5068–5073CrossRefGoogle Scholar
  6. 6.
    Shin H, Jo S, Mikos AG (2003) Biomimetic materials for tissue engineering. Biomaterials 24(24):4353–4364CrossRefGoogle Scholar
  7. 7.
    Seal B, Otero T, Panitch A (2001) Polymeric biomaterials for tissue and organ regeneration. Mater Sci Eng R Rep 34(4):147–230CrossRefGoogle Scholar
  8. 8.
    Lutolf M, Hubbell J (2005) Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 23(1):47–55CrossRefGoogle Scholar
  9. 9.
    Nair LS, Laurencin CT (2005) Polymers as biomaterials for tissue engineering and controlled drug delivery. In: Tissue engineering I. Springer, Berlin, pp 47–90Google Scholar
  10. 10.
    Nair LS, Laurencin CT (2007) Biodegradable polymers as biomaterials. Prog Polym Sci 32(8):762–798CrossRefGoogle Scholar
  11. 11.
    Malafaya PB, Silva GA, Reis RL (2007) Natural–origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv Drug Deliv Rev 59(4):207–233CrossRefGoogle Scholar
  12. 12.
    Kundu B, Rajkhowa R, Kundu SC, Wang X (2013) Silk fibroin biomaterials for tissue regenerations. Adv Drug Deliv Rev 65(4):457–470CrossRefGoogle Scholar
  13. 13.
    Mondal M (2007) The silk proteins, sericin and fibroin in silkworm, Bombyx mori Linn., a review. Caspian J Environ Sci 5(2):63–76Google Scholar
  14. 14.
    Yan L-P, Silva-Correia J, Oliveira MB, Vilela C, Pereira H, Sousa RA, Mano JF, Oliveira AL, Oliveira JM, Reis RL (2015) Bilayered silk/silk-nanoCaP scaffolds for osteochondral tissue engineering: in vitro and in vivo assessment of biological performance. Acta Biomater 12:227–241CrossRefGoogle Scholar
  15. 15.
    Ribeiro VP, Silva-Correia J, Nascimento AI, da Silva MA, Marques AP, Ribeiro AS, Silva CJ, Bonifácio G, Sousa RA, Oliveira JM (2017) Silk-based anisotropical 3D biotextiles for bone regeneration. Biomaterials 123:92–106CrossRefGoogle Scholar
  16. 16.
    Chirila TV, Barnard Z, Harkin DG, Schwab IR, Hirst LW (2008) Bombyx mori silk fibroin membranes as potential substrata for epithelial constructs used in the management of ocular surface disorders. Tissue Eng Part A 14(7):1203–1211CrossRefGoogle Scholar
  17. 17.
    Z-x C, X-m M, K-h Z, L-p F, A-l Y, He C-l, Wang H-s (2010) Fabrication of chitosan/silk fibroin composite nanofibers for wound-dressing applications. Int J Mol Sci 11(9):3529–3539CrossRefGoogle Scholar
  18. 18.
    Kundu B, Kundu SC (2012) Silk sericin/polyacrylamide in situ forming hydrogels for dermal reconstruction. Biomaterials 33(30):7456–7467CrossRefGoogle Scholar
  19. 19.
    Mandal BB, Ghosh B, Kundu S (2011) Non-mulberry silk sericin/poly (vinyl alcohol) hydrogel matrices for potential biotechnological applications. Int J Biol Macromol 49(2):125–133CrossRefGoogle Scholar
  20. 20.
    Zhang Y-Q (2002) Applications of natural silk protein sericin in biomaterials. Biotechnol Adv 20(2):91–100CrossRefGoogle Scholar
  21. 21.
    Sirichaisit J, Young R, Vollrath F (2000) Molecular deformation in spider dragline silk subjected to stress. Polymer 41(3):1223–1227CrossRefGoogle Scholar
  22. 22.
    Ribeiro VP, Almeida LR, Martins AR, Pashkuleva I, Marques AP, Ribeiro AS, Silva CJ, Bonifácio G, Sousa RA, Reis RL (2016) Influence of different surface modification treatments on silk biotextiles for tissue engineering applications. J Biomed Mater Res B Appl Biomater 104(3):496–507CrossRefGoogle Scholar
  23. 23.
    Luangbudnark W, Viyoch J, Laupattarakasem W, Surakunprapha P, Laupattarakasem P (2012) Properties and biocompatibility of chitosan and silk fibroin blend films for application in skin tissue engineering. ScientificWorldJournal 2012:697201CrossRefGoogle Scholar
  24. 24.
    Yan LP, Oliveira JM, Oliveira AL, Reis RL (2017) Core-shell silk hydrogels with spatially tuned conformations as drug-delivery system. J Tissue Eng Regen Med 11(11):3168–3177CrossRefGoogle Scholar
  25. 25.
    Sahoo S, Toh SL, Goh JC (2010) A bFGF-releasing silk/PLGA-based biohybrid scaffold for ligament/tendon tissue engineering using mesenchymal progenitor cells. Biomaterials 31(11):2990–2998CrossRefGoogle Scholar
  26. 26.
    Yan L-P, Oliveira JM, Oliveira AL, Caridade SG, Mano JF, Reis RL (2012) Macro/microporous silk fibroin scaffolds with potential for articular cartilage and meniscus tissue engineering applications. Acta Biomater 8(1):289–301CrossRefGoogle Scholar
  27. 27.
    Nukavarapu SP, Dorcemus DL (2013) Osteochondral tissue engineering: current strategies and challenges. Biotechnol Adv 31(5):706–721CrossRefGoogle Scholar
  28. 28.
    Jeong CG, Zhang H, Hollister SJ (2012) Three-dimensional polycaprolactone scaffold-conjugated bone morphogenetic protein-2 promotes cartilage regeneration from primary chondrocytes in vitro and in vivo without accelerated endochondral ossification. J Biomed Mater Res A 100(8):2088–2096CrossRefGoogle Scholar
  29. 29.
    Malda J, Woodfield T, Van Der Vloodt F, Wilson C, Martens D, Tramper J, Van Blitterswijk C, Riesle J (2005) The effect of PEGT/PBT scaffold architecture on the composition of tissue engineered cartilage. Biomaterials 26(1):63–72CrossRefGoogle Scholar
  30. 30.
    Zhou J, Xu C, Wu G, Cao X, Zhang L, Zhai Z, Zheng Z, Chen X, Wang Y (2011) In vitro generation of osteochondral differentiation of human marrow mesenchymal stem cells in novel collagen–hydroxyapatite layered scaffolds. Acta Biomater 7(11):3999–4006CrossRefGoogle Scholar
  31. 31.
    Yan L-P, Salgado AJ, Oliveira JM, Oliveira AL, Reis RL (2013) De novo bone formation on macro/microporous silk and silk/nano-sized calcium phosphate scaffolds. J Bioact Compat Polym 28(5):439–452CrossRefGoogle Scholar
  32. 32.
    Tan H, Chu CR, Payne KA, Marra KG (2009) Injectable in situ forming biodegradable chitosan–hyaluronic acid based hydrogels for cartilage tissue engineering. Biomaterials 30(13):2499–2506CrossRefGoogle Scholar
  33. 33.
    Oliveira JM, Rodrigues MT, Silva SS, Malafaya PB, Gomes ME, Viegas CA, Dias IR, Azevedo JT, Mano JF, Reis RL (2006) Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue-engineering applications: scaffold design and its performance when seeded with goat bone marrow stromal cells. Biomaterials 27(36):6123–6137CrossRefGoogle Scholar
  34. 34.
    Chen J, Chen H, Li P, Diao H, Zhu S, Dong L, Wang R, Guo T, Zhao J, Zhang J (2011) Simultaneous regeneration of articular cartilage and subchondral bone in vivo using MSCs induced by a spatially controlled gene delivery system in bilayered integrated scaffolds. Biomaterials 32(21):4793–4805. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Jeon JE, Vaquette C, Klein TJ, Hutmacher DW (2014) Perspectives in Multiphasic Osteochondral Tissue Engineering. Anat Rec 297(1):26–35. CrossRefGoogle Scholar
  36. 36.
    Pereira DR, Canadas RF, Silva-Correia J, Marques AP, Reis RL, Oliveira JM (2014) Gellan gum-based hydrogel bilayered scaffolds for osteochondral tissue engineering. In: Key engineering materials. Trans Tech, Stafa-Zurich, pp 255–260CrossRefGoogle Scholar
  37. 37.
    Rodrigues MT, Lee SJ, Gomes ME, Reis RL, Atala A, Yoo JJ (2012) Bilayered constructs aimed at osteochondral strategies: the influence of medium supplements in the osteogenic and chondrogenic differentiation of amniotic fluid-derived stem cells. Acta Biomater 8(7):2795–2806CrossRefGoogle Scholar
  38. 38.
    Ding X, Zhu M, Xu B, Zhang J, Zhao Y, Ji S, Wang L, Wang L, Li X, Kong D, Ma X, Yang Q (2014) Integrated trilayered silk fibroin scaffold for osteochondral differentiation of adipose-derived stem cells. ACS Appl Mater Interfaces 6(19):16696–16705. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Saha S, Kundu B, Kirkham J, Wood D, Kundu SC, Yang XB (2013) Osteochondral tissue engineering in vivo: a comparative study using layered silk fibroin scaffolds from mulberry and nonmulberry silkworms. PLoS One 8(11):e80004CrossRefGoogle Scholar
  40. 40.
    Koh L-D, Cheng Y, Teng C-P, Khin Y-W, Loh X-J, Tee S-Y, Low M, Ye E, Yu H-D, Zhang Y-W (2015) Structures, mechanical properties and applications of silk fibroin materials. Prog Polym Sci 46:86–110CrossRefGoogle Scholar
  41. 41.
    Simmons AH, Michal CA, Jelinski LW (1996) Molecular orientation and two-component nature of the crystalline fraction of spider dragline silk. Science 271(5245):84CrossRefGoogle Scholar
  42. 42.
    Zhang Q, Yan S, Li M (2009) Silk fibroin based porous materials. Materials 2(4):2276–2295CrossRefGoogle Scholar
  43. 43.
    McGill M, Coburn JM, Partlow BP, Mu X, Kaplan DL (2017) Molecular and macro-scale analysis of enzyme-crosslinked silk hydrogels for rational biomaterial design. Acta Biomater 63:76–84CrossRefGoogle Scholar
  44. 44.
    Hu Y, Zhang Q, You R, Wang L, Li M (2012) The relationship between secondary structure and biodegradation behavior of silk fibroin scaffolds. Adv Mater Sci Eng 2012Google Scholar
  45. 45.
    Wilson D, Valluzzi R, Kaplan D (2000) Conformational transitions in model silk peptides. Biophys J 78(5):2690–2701CrossRefGoogle Scholar
  46. 46.
    Valluzzi R, Gido SP, Zhang W, Muller WS, Kaplan DL (1996) Trigonal crystal structure of Bombyx mori silk incorporating a threefold helical chain conformation found at the air–water interface. Macromolecules 29(27):8606–8614CrossRefGoogle Scholar
  47. 47.
    Geckil H, Xu F, Zhang X, Moon S, Demirci U (2010) Engineering hydrogels as extracellular matrix mimics. Nanomedicine 5(3):469–484CrossRefGoogle Scholar
  48. 48.
    Guarino V, Gloria A, Raucci MG, Ambrosio L (2012) Hydrogel-based platforms for the regeneration of osteochondral tissue and intervertebral disc. Polymer 4(3):1590–1612CrossRefGoogle Scholar
  49. 49.
    Jeon O, Bouhadir KH, Mansour JM, Alsberg E (2009) Photocrosslinked alginate hydrogels with tunable biodegradation rates and mechanical properties. Biomaterials 30(14):2724–2734CrossRefGoogle Scholar
  50. 50.
    Yan L-P, Silva-Correia J, Ribeiro VP, Miranda-Gonçalves V, Correia C, da Silva MA, Sousa RA, Reis RM, Oliveira AL, Oliveira JM (2016) Tumor growth suppression induced by biomimetic silk fibroin hydrogels. Sci Rep 6:31037CrossRefGoogle Scholar
  51. 51.
    Huang S, Fu X (2010) Naturally derived materials-based cell and drug delivery systems in skin regeneration. J Control Release 142(2):149–159CrossRefGoogle Scholar
  52. 52.
    Chen X, Li W, Zhong W, Lu Y, Yu T (1997) pH sensitivity and ion sensitivity of hydrogels based on complex-forming chitosan/silk fibroin interpenetrating polymer network. J Appl Polym Sci 65(11):2257–2262CrossRefGoogle Scholar
  53. 53.
    Guziewicz N, Best A, Perez-Ramirez B, Kaplan DL (2011) Lyophilized silk fibroin hydrogels for the sustained local delivery of therapeutic monoclonal antibodies. Biomaterials 32(10):2642–2650CrossRefGoogle Scholar
  54. 54.
    Yucel T, Cebe P, Kaplan DL (2009) Vortex-induced injectable silk fibroin hydrogels. Biophys J 97(7):2044–2050CrossRefGoogle Scholar
  55. 55.
    Kim U-J, Park J, Li C, Jin H-J, Valluzzi R, Kaplan DL (2004) Structure and properties of silk hydrogels. Biomacromolecules 5(3):786–792CrossRefGoogle Scholar
  56. 56.
    Teixeira LSM, Feijen J, van Blitterswijk CA, Dijkstra PJ, Karperien M (2012) Enzyme-catalyzed crosslinkable hydrogels: emerging strategies for tissue engineering. Biomaterials 33(5):1281–1290CrossRefGoogle Scholar
  57. 57.
    Singh YP, Bhardwaj N, Mandal BB (2016) Potential of agarose/silk fibroin blended hydrogel for in vitro cartilage tissue engineering. ACS Appl Mater Interfaces 8(33):21236–21249CrossRefGoogle Scholar
  58. 58.
    Kasoju N, Bora U (2012) Silk fibroin in tissue engineering. Adv Healthc Mater 1(4):393–412CrossRefGoogle Scholar
  59. 59.
    Zhang W, Lian Q, Li D, Wang K, Hao D, Bian W, He J, Jin Z (2014) Cartilage repair and subchondral bone migration using 3D printing osteochondral composites: a one-year-period study in rabbit trochlea. Biomed Res Int 2014:746138PubMedPubMedCentralGoogle Scholar
  60. 60.
    Fini M, Motta A, Torricelli P, Giavaresi G, Aldini NN, Tschon M, Giardino R, Migliaresi C (2005) The healing of confined critical size cancellous defects in the presence of silk fibroin hydrogel. Biomaterials 26(17):3527–3536CrossRefGoogle Scholar
  61. 61.
    Kim HJ, Kim U-J, Kim HS, Li C, Wada M, Leisk GG, Kaplan DL (2008) Bone tissue engineering with premineralized silk scaffolds. Bone 42(6):1226–1234CrossRefGoogle Scholar
  62. 62.
    Gentile P, Chiono V, Carmagnola I, Hatton PV (2014) An overview of poly (lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering. Int J Mol Sci 15(3):3640–3659CrossRefGoogle Scholar
  63. 63.
    Zhang W, Wang X, Wang S, Zhao J, Xu L, Zhu C, Zeng D, Chen J, Zhang Z, Kaplan DL (2011) The use of injectable sonication-induced silk hydrogel for VEGF 165 and BMP-2 delivery for elevation of the maxillary sinus floor. Biomaterials 32(35):9415–9424CrossRefGoogle Scholar
  64. 64.
    Tetteh ES, Bajaj S, Ghodadra NS, Cole BJ (2012) The basic science and surgical treatment options for articular cartilage injuries of the knee. J Orthopaed Sports Phys Ther 42(3):243–253CrossRefGoogle Scholar
  65. 65.
    Ribeiro V, Pina S, Oliveira JM, Reis RL (2017) Fundamentals on Osteochondral Tissue engineering. In: Regenerative strategies for the treatment of knee joint disabilities. Springer, Berlin, pp 129–146Google Scholar
  66. 66.
    Weiss P, Fatimi A, Guicheux J, Vinatier C (2010) Hydrogels for cartilage tissue engineering. In: Biomedical applications of hydrogels handbook. Springer, Berlin, pp 247–268CrossRefGoogle Scholar
  67. 67.
    Floren M, Migliaresi C, Motta A (2016) Processing techniques and applications of silk hydrogels in bioengineering. J Funct Biomater 7(3):26CrossRefGoogle Scholar
  68. 68.
    Chao PHG, Yodmuang S, Wang X, Sun L, Kaplan DL, Vunjak-Novakovic G (2010) Silk hydrogel for cartilage tissue engineering. J Biomed Mater Res B Appl Biomater 95(1):84–90CrossRefGoogle Scholar
  69. 69.
    Mauck RL, Soltz MA, Wang CC, Wong DD, Chao P-HG, Valhmu WB, Hung CT, Ateshian GA (2000) Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng 122(3):252–260CrossRefGoogle Scholar
  70. 70.
    Park S-H, Cho H, Gil ES, Mandal BB, Min B-H, Kaplan DL (2011) Silk-fibrin/hyaluronic acid composite gels for nucleus pulposus tissue regeneration. Tissue Eng Part A 17(23–24):2999–3009CrossRefGoogle Scholar
  71. 71.
    Yodmuang S, McNamara SL, Nover AB, Mandal BB, Agarwal M, Kelly T-AN, Chao P-hG, Hung C, Kaplan DL, Vunjak-Novakovic G (2015) Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair. Acta Biomater 11:27–36CrossRefGoogle Scholar
  72. 72.
    Holland TA, Bodde EW, Baggett LS, Tabata Y, Mikos AG, Jansen JA (2005) Osteochondral repair in the rabbit model utilizing bilayered, degradable oligo (poly (ethylene glycol) fumarate) hydrogel scaffolds. J Biomed Mater Res A 75(1):156–167CrossRefGoogle Scholar
  73. 73.
    Guo X, Park H, Liu G, Liu W, Cao Y, Tabata Y, Kasper FK, Mikos AG (2009) In vitro generation of an osteochondral construct using injectable hydrogel composites encapsulating rabbit marrow mesenchymal stem cells. Biomaterials 30(14):2741–2752CrossRefGoogle Scholar
  74. 74.
    Kim K, Lam J, Lu S, Spicer PP, Lueckgen A, Tabata Y, Wong ME, Jansen JA, Mikos AG, Kasper FK (2013) Osteochondral tissue regeneration using a bilayered composite hydrogel with modulating dual growth factor release kinetics in a rabbit model. J Control Release 168(2):166–178CrossRefGoogle Scholar
  75. 75.
    Lu S, Lam J, Trachtenberg JE, Lee EJ, Seyednejad H, van den Beucken JJ, Tabata Y, Wong ME, Jansen JA, Mikos AG (2014) Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair. Biomaterials 35(31):8829–8839CrossRefGoogle Scholar
  76. 76.
    Grayson WL, Chao P-HG, Marolt D, Kaplan DL, Vunjak-Novakovic G (2008) Engineering custom-designed osteochondral tissue grafts. Trends Biotechnol 26(4):181–189CrossRefGoogle Scholar
  77. 77.
    Das S, Pati F, Choi Y-J, Rijal G, Shim J-H, Kim SW, Ray AR, Cho D-W, Ghosh S (2015) Bioprintable, cell-laden silk fibroin–gelatin hydrogel supporting multilineage differentiation of stem cells for fabrication of three-dimensional tissue constructs. Acta Biomater 11:233–246CrossRefGoogle Scholar
  78. 78.
    Thorrez L, Shansky J, Wang L, Fast L, VandenDriessche T, Chuah M, Mooney D, Vandenburgh H (2008) Growth, differentiation, transplantation and survival of human skeletal myofibers on biodegradable scaffolds. Biomaterials 29(1):75–84. CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Karageorgiou V, Kaplan D (2005) Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 26:5474–5491CrossRefGoogle Scholar
  80. 80.
    van de Witte P, Dijkstra P, vanden Berg J, Feijen J (1996) Phase separation processes in polymer solutions in relation to membrane formation. J Membr Sci 117:1–31CrossRefGoogle Scholar
  81. 81.
    Marrella A, Cavo M, Scaglione S (2017) Rapid prototyping for the engineering of osteochondral tissues. In: Oliveira JM, Reis RL (eds) Regenerative strategies for the treatment of knee joint disabilities. Springer International, Cham, pp 163–185. CrossRefGoogle Scholar
  82. 82.
    Oliveira AL, Sampaio SC, Sousa RA, Reis RL (2006) Controlled mineralization of nature-inspired silk fibroin/hydroxyapatite hybrid bioactive scafolds for bone tissue engineering applications. Paper presented at the 20th European Conference on Biomaterials, Nantes, France, 27 September–1 OctoberGoogle Scholar
  83. 83.
    Abdelaal O, Darwish S (2011) Fabrication of tissue engineering scaffolds using rapid prototyping techniques. World Acad Sci Eng Technol 59:577–585Google Scholar
  84. 84.
    Chae T, Yang H, Leung V, Ko F, Troczynski T (2013) Novel biomimetic hydroxyapatite/alginate nanocomposite fibrous scaffolds for bone tissue regeneration. J Mater Sci Mater Med 24:1885–1894CrossRefGoogle Scholar
  85. 85.
    Cui L, Zhang N, Cui W, Zhang P, Chen X (2015) A novel nano/micro-fibrous scaffold by melt-spinning method for bone tissue engineering. J Bionic Eng 12(1):117–128CrossRefGoogle Scholar
  86. 86.
    Cardea S, Scognamiglio M, Reverchon E (2016) Supercritical fluid assisted process for the generation of cellulose acetate loaded structures, potentially useful for tissue engineering applications. Mater Sci Eng C 59:480–487CrossRefGoogle Scholar
  87. 87.
    Yan L, Oliveira J, Oliveira A, Reis R (2014) Silk fibroin/nano-CaP bilayered scaffolds for osteochondral tissue engineering. Key Eng Mater 587:245. CrossRefGoogle Scholar
  88. 88.
    Yan LP, 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(4):888–898. CrossRefPubMedGoogle Scholar
  89. 89.
    Chen K, Shi P, Teh TKH, Toh SL, Goh JCH (2016) In vitro generation of a multilayered osteochondral construct with an osteochondral interface using rabbit bone marrow stromal cells and a silk peptide-based scaffold. J Tissue Eng Regen Med 10(4):284–293. CrossRefPubMedGoogle Scholar
  90. 90.
    Kazemnejad S, Khanmohammadi M, Mobini S, Taghizadeh-Jahed M, Khanjani S, Arasteh S, Golshahi H, Torkaman G, Ravanbod R, Heidari-Vala H, Moshiri A, Tahmasebi M-N, Akhondi M-M (2016) Comparative repair capacity of knee osteochondral defects using regenerated silk fiber scaffolds and fibrin glue with/without autologous chondrocytes during 36 weeks in rabbit model. Cell Tissue Res 364(3):559–572. CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Mobini S, Hoyer B, Solati-Hashjin M, Lode A, Nosoudi N, Samadikuchaksaraei A, Gelinsky M (2013) Fabrication and characterization of regenerated silk scaffolds reinforced with natural silk fibers for bone tissue engineering. J Biomed Mater Res A 101A(8):2392–2404. CrossRefGoogle Scholar
  92. 92.
    Zhou F, Zhang X, Cai D, Li J, Mu Q, Zhang W, Zhu S, Jiang Y, Shen W, Zhang S, Ouyang HW (2017) Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair. Acta Biomater 63(Supplement C):64–75. CrossRefPubMedGoogle Scholar
  93. 93.
    Pina S, Canadas RF, Jiménez G, Perán M, Marchal JA, Reis RL, Oliveira JM (2017) Biofunctional ionic-doped calcium phosphates: silk fibroin composites for bone tissue engineering scaffolding. Cells Tissues Organs 204(3–4):150–163CrossRefGoogle Scholar
  94. 94.
    Çakmak S, Çakmak AS, Kaplan DL, Gümüşderelioğlu M (2016) A silk fibroin and peptide amphiphile-based co-culture model for osteochondral tissue engineering. Macromol Biosci 16(8):1212–1226. CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Viviana P. Ribeiro
    • 1
    • 2
    Email author
  • Sandra Pina
    • 1
    • 2
  • J. Miguel Oliveira
    • 1
    • 2
    • 3
  • Rui L. Reis
    • 1
    • 2
    • 3
  1. 1.3B’s Research Group—Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineBarco, GuimarãesPortugal
  2. 2.ICVS/3B’s—PT Government Associate LaboratoryBraga/GuimarãesPortugal
  3. 3.The Discoveries Centre for Regenerative and Precision MedicineHeadquarters at University of MinhoBarco, GuimarãesPortugal

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