Advertisement

Silk-Based Hydrogels for Biomedical Applications

  • Bianca Galateanu
  • Ariana Hudita
  • Catalin Zaharia
  • Mihaela-Cristina Bunea
  • Eugenia Vasile
  • Mihaela-Ramona Buga
  • Marieta Costache
Living reference work entry
Part of the Polymers and Polymeric Composites: A Reference Series book series (POPOC)

Abstract

Among the naturally occurring fibers, silk occupies a special position due to its properties. Silk fibroins, the unique proteins of silkworm fibers, are high-molecular-weight block copolymers consisting of a heavy (~370 kDa) and a light (~26 kDa) chain with varying amphiphilicity linked by a single disulphide bond. Bombyx mori silk is the most characterized silkworm silk. Researchers have investigated fibroin as one of the promising resources of biotechnology and biomedical materials due to its other unique properties including excellent biocompatibility, favorable oxygen permeability, and outstanding biodegradability, and the degradation product can be readily absorbed by the body with minimal inflammatory reaction. Silk hydrogels have been thoroughly studied for potential biotechnological applications due to their mechanical properties, biocompatibility, controllable degradation rates, and self-assembly into β-sheet networks. Hydrogels made from silk proteins have shown a potential in overcoming limitations of hydrogels prepared from conventional polymers. This chapter offers overview of the recent developments in silk protein-based hydrogels, both of fibroin and sericin proteins. It describes the approaches for obtaining silk hydrogels and ideas to improve the existing properties or to incorporate new features in the hydrogels by making composites. Characterization tools and modern bioapplications of the silk hydrogels for tissue engineering and controlled release are also reviewed. A special focus is given to silk fibroin composite hydrogels for bone tissue engineering applications.

Keywords

Silk fibroin Graphene oxide Composite hydrogels Bone tissue engineering Biocompatibility 

References

  1. 1.
    Stoppel WL, Raia N, Kimmerling E, Wang S, Ghezzi CE, Kaplan DL (2017) 2.12 Silk biomaterials. In: Ducheyne P, Healy K, Hutmacher DW, Grainger DW, Kirkpatrick CJ (eds) Comprehensive biomaterials II. Elsevier, Amsterdam, pp 253–278CrossRefGoogle Scholar
  2. 2.
    Naskar D, Barua RR, Ghosh AK, Kundu SC (2014) 1 – Introduction to silk biomaterials. In: Kundu SC (ed) Silk biomaterials for tissue engineering and regenerative medicine. Woodhead Publishing, Amsterdam, pp 3–40CrossRefGoogle Scholar
  3. 3.
    Kundu B, Rajkhowa R, Kundu SC, Wang X (2013) Silk fibroin biomaterials for tissue regenerations. Adv Drug Deliv Rev 65(4):457–470.  https://doi.org/10.1016/j.addr.2012.09.043CrossRefPubMedGoogle Scholar
  4. 4.
    Huang Y, Bailey K, Wang S, Feng X (2017) Silk fibroin films for potential applications in controlled release. React Funct Polym 116(Suppl C):57–68.  https://doi.org/10.1016/j.reactfunctpolym.2017.05.007CrossRefGoogle Scholar
  5. 5.
    Shimura K, Kikuchi A, Ohtomo K, Katagata Y, Hyodo A (1976) Studies on silk fibroin of Bombyx mori. I. Fractionation of fibroin prepared from the posterior silk gland. J Biochem 80(4):693–702CrossRefPubMedGoogle Scholar
  6. 6.
    Tanaka K, Inoue S, Mizuno S (1999) Hydrophobic interaction of P25, containing Asn-linked oligosaccharide chains, with the H-L complex of silk fibroin produced by Bombyx mori. Insect Biochem Mol Biol 29(3):269–276CrossRefPubMedGoogle Scholar
  7. 7.
    Sehnal F, Žurovec M (2004) Construction of silk fiber core in lepidoptera. Biomacromolecules 5(3):666–674.  https://doi.org/10.1021/bm0344046CrossRefPubMedGoogle Scholar
  8. 8.
    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, Han M-Y (2015) Structures, mechanical properties and applications of silk fibroin materials. Prog Polym Sci 46(Suppl C):86–110.  https://doi.org/10.1016/j.progpolymsci.2015.02.001CrossRefGoogle Scholar
  9. 9.
    Kapoor S, Kundu SC (2016) Silk protein-based hydrogels: promising advanced materials for biomedical applications. Acta Biomater 31:17–32.  https://doi.org/10.1016/j.actbio.2015.11.034CrossRefPubMedGoogle Scholar
  10. 10.
    Raia NR, Partlow BP, McGill M, Kimmerling EP, Ghezzi CE, Kaplan DL (2017) Enzymatically crosslinked silk-hyaluronic acid hydrogels. Biomaterials 131(Suppl C):58–67.  https://doi.org/10.1016/j.biomaterials.2017.03.046CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Numata K (2014) 19 – Silk hydrogels for tissue engineering and dual-drug delivery. In: Kundu SC (ed) Silk biomaterials for tissue engineering and regenerative medicine. Woodhead Publishing, Amsterdam, pp 503–518CrossRefGoogle Scholar
  12. 12.
    Zhang C, Chen X, Shao Z (2016) Sol–gel transition of regenerated silk fibroins in ionic liquid/water mixtures. ACS Biomater Sci Eng 2(1):12–18.  https://doi.org/10.1021/acsbiomaterials.5b00149CrossRefGoogle Scholar
  13. 13.
    Ming J, Jiang Z, Wang P, Bie S, Zuo B (2015) Silk fibroin/sodium alginate fibrous hydrogels regulated hydroxyapatite crystal growth. Mater Sci Eng C 51(Suppl C):287–293.  https://doi.org/10.1016/j.msec.2015.03.014CrossRefGoogle Scholar
  14. 14.
    Wu J, Liu J, Shi Y, Wan Y (2016) Rheological, mechanical and degradable properties of injectable chitosan/silk fibroin/hydroxyapatite/glycerophosphate hydrogels. J Mech Behav Biomed Mater 64:161–172.  https://doi.org/10.1016/j.jmbbm.2016.07.007CrossRefPubMedGoogle Scholar
  15. 15.
    Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A (2015) Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials 73(Suppl C):254–271.  https://doi.org/10.1016/j.biomaterials.2015.08.045CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Wang J, Yang Q, Cheng N, Tao X, Zhang Z, Sun X, Zhang Q (2016) Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair. Mater Sci Eng C Mater Biol Appl 61(Suppl C):705–711.  https://doi.org/10.1016/j.msec.2015.12.097CrossRefPubMedGoogle Scholar
  17. 17.
    Joo Kim H, Kim H, Matsumoto A, Chin I-J, Jin H-J, Kaplan D (2005) Processing windows for forming silk fibroin biomaterials into a 3D porous matrix. Aust J Chem 58:716–720.  https://doi.org/10.1071/CH05170CrossRefGoogle Scholar
  18. 18.
    Horan RL, Antle K, Collette AL, Wang Y, Huang J, Moreau JE, Volloch V, Kaplan DL, Altman GH (2005) In vitro degradation of silk fibroin. Biomaterials 26(17):3385–3393.  https://doi.org/10.1016/j.biomaterials.2004.09.020CrossRefPubMedGoogle Scholar
  19. 19.
    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):289–301.  https://doi.org/10.1016/j.actbio.2011.09.037CrossRefPubMedGoogle Scholar
  20. 20.
    Bhumiratana S, Grayson WL, Castaneda A, Rockwood DN, Gil ES, Kaplan DL, Vunjak-Novakovic G (2011) Nucleation and growth of mineralized bone matrix on silk-hydroxyapatite composite scaffolds. Biomaterials 32(11):2812–2820.  https://doi.org/10.1016/j.biomaterials.2010.12.058CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Hofmann S, Knecht S, Langer R, Kaplan DL, Vunjak-Novakovic G, Merkle HP, Meinel L (2006) Cartilage-like tissue engineering using silk scaffolds and mesenchymal stem cells. Tissue Eng 12(10):2729–2738.  https://doi.org/10.1089/ten.2006.12.2729CrossRefPubMedGoogle Scholar
  22. 22.
    Wang Y, Blasioli DJ, Kim H-J, Kim HS, Kaplan DL (2006) Cartilage tissue engineering with silk scaffolds and human articular chondrocytes. Biomaterials 27(25):4434–4442.  https://doi.org/10.1016/j.biomaterials.2006.03.050CrossRefPubMedGoogle Scholar
  23. 23.
    Mauney JR, Nguyen T, Gillen K, Kirker-Head C, Gimble JM, Kaplan DL (2007) Engineering adipose-like tissue in vitro and in vivo utilizing human bone marrow and adipose-derived mesenchymal stem cells with silk fibroin 3D scaffolds. Biomaterials 28(35):5280–5290.  https://doi.org/10.1016/j.biomaterials.2007.08.017CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Kang JH, Gimble JM, Kaplan DL (2009) In vitro 3D model for human vascularized adipose tissue. Tissue Eng Part A 15(8):2227–2236.  https://doi.org/10.1089/ten.tea.2008.0469CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lovett M, Eng G, Kluge JA, Cannizzaro C, Vunjak-Novakovic G, Kaplan DL (2010) Tubular silk scaffolds for small diameter vascular grafts. Organogenesis 6(4):217–224.  https://doi.org/10.4161/org.6.4.13407CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Chen J, Altman GH, Karageorgiou V, Horan R, Collette A, Volloch V, Colabro T, Kaplan DL (2003) Human bone marrow stromal cell and ligament fibroblast responses on RGD-modified silk fibers. J Biomed Mater Res A 67(2):559–570.  https://doi.org/10.1002/jbm.a.10120CrossRefPubMedGoogle Scholar
  27. 27.
    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):2483–2492.  https://doi.org/10.1016/j.actbio.2012.03.019CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ren Y-J, Zhou Z-Y, Liu B-F, Xu Q-Y, Cui F-Z (2009) Preparation and characterization of fibroin/hyaluronic acid composite scaffold. Int J Biol Macromol 44(4):372–378.  https://doi.org/10.1016/j.ijbiomac.2009.02.004CrossRefPubMedGoogle Scholar
  29. 29.
    Lun B, Jianmei X, Qilong S, Chuanxia D, Jiangchao S, Zhengyu W (2007) On the growth model of the capillaries in the porous silk fibroin films. J Mater Sci Mater Med 18(10): 1917–1921.  https://doi.org/10.1007/s10856-007-3105-7CrossRefPubMedGoogle Scholar
  30. 30.
    Lu Q, Hu K, Feng Q, Cui F (2009) Growth of fibroblast and vascular smooth muscle cells in fibroin/collagen scaffold. Mater Sci Eng C 29:2239–2245.  https://doi.org/10.1016/j.msec.2009.05.014CrossRefGoogle Scholar
  31. 31.
    Lu Q, Zhang S, Hu K, Feng Q, Cao C, Cui F (2007) Cytocompatibility and blood compatibility of multifunctional fibroin/collagen/heparin scaffolds. Biomaterials 28(14):2306–2313.  https://doi.org/10.1016/j.biomaterials.2007.01.031CrossRefPubMedGoogle Scholar
  32. 32.
    Lv Q, Hu K, Feng Q, Cui F, Cao C (2007) Preparation and characterization of PLA/fibroin composite and culture of HepG2 (human hepatocellular liver carcinoma cell line) cells. Compos Sci Technol 67(14):3023–3030.  https://doi.org/10.1016/j.compscitech.2007.05.003CrossRefGoogle Scholar
  33. 33.
    Hu K, Lv Q, Cui FZ, Feng QL, Kong XD, Wang HL, Huang LY, Li T (2006) Biocompatible fibroin blended films with recombinant human-like collagen for hepatic tissue engineering. J Bioact Compat Polym 21(1):23–37.  https://doi.org/10.1177/0883911506060455CrossRefGoogle Scholar
  34. 34.
    Vasconcelos A, Freddi G, Cavaco-Paulo A (2008) Biodegradable materials based on silk fibroin and keratin. Biomacromolecules 9(4):1299–1305.  https://doi.org/10.1021/bm7012789CrossRefPubMedGoogle Scholar
  35. 35.
    Kweon H, Ha HC, Um IC, Park YH (2001) Physical properties of silk fibroin/chitosan blend films. J Appl Polym Sci 80(7):928–934.  https://doi.org/10.1002/app.1172CrossRefGoogle Scholar
  36. 36.
    Foss C, Merzari E, Migliaresi C, Motta A (2013) Silk fibroin/hyaluronic acid 3D matrices for cartilage tissue engineering. Biomacromolecules 14(1):38–47.  https://doi.org/10.1021/bm301174xCrossRefPubMedGoogle Scholar
  37. 37.
    Whitesides GM, Wong AP (2006) The intersection of biology and materials science. MRS Bull 31(1):19–27.  https://doi.org/10.1557/mrs2006.2CrossRefGoogle Scholar
  38. 38.
    Zaharia C, Tudora M-R, Stancu I-C, Galateanu B, Lungu A, Cincu C (2012) Characterization and deposition behavior of silk hydrogels soaked in simulated body fluid. Mater Sci Eng C 32(4):945–952.  https://doi.org/10.1016/j.msec.2012.02.018CrossRefGoogle Scholar
  39. 39.
    Wu S, Liu X, Yeung KWK, Liu C, Yang X (2014) Biomimetic porous scaffolds for bone tissue engineering. Mater Sci Eng R 80(Suppl C):1–36.  https://doi.org/10.1016/j.mser.2014.04.001CrossRefGoogle Scholar
  40. 40.
    Miyamoto S, Koyanagi R, Nakazawa Y, Nagano A, Abiko Y, Inada M, Miyaura C, Asakura T (2013) Bombyx mori silk fibroin scaffolds for bone regeneration studied by bone differentiation experiment. J Biosci Bioeng 115(5):575–578.  https://doi.org/10.1016/j.jbiosc.2012.11.021CrossRefPubMedGoogle Scholar
  41. 41.
    Nair LS, Laurencin CT (2007) Biodegradable polymers as biomaterials. Prog Polym Sci 32(8):762–798.  https://doi.org/10.1016/j.progpolymsci.2007.05.017CrossRefGoogle Scholar
  42. 42.
    Li M, Li J (2014) 12 – Biodegradation behavior of silk biomaterials. In: Kundu SC (ed) Silk biomaterials for tissue engineering and regenerative medicine. Woodhead Publishing, Amsterdam, pp 330–348CrossRefGoogle Scholar
  43. 43.
    Wintterlin J, Bocquet M-L (2009) Graphene on metal surfaces. Surf Sci 603(10):1841–1852.  https://doi.org/10.1016/j.susc.2008.08.037CrossRefGoogle Scholar
  44. 44.
    Geim AK, Novoselov KS (2007) The rise of graphene. Nat Mater 6(3):183–191.  https://doi.org/10.1038/nmat1849CrossRefPubMedGoogle Scholar
  45. 45.
    Steurer P, Wissert R, Thomann R, Mülhaupt R (2009) Functionalized graphenes and thermoplastic nanocomposites based upon expanded graphite oxide. Macromol Rapid Commun 30(4–5):316–327.  https://doi.org/10.1002/marc.200800754CrossRefPubMedGoogle Scholar
  46. 46.
    Singh V, Joung D, Zhai L, Das S, Khondaker SI, Seal S (2011) Graphene based materials: past, present and future. Prog Mater Sci 56(8):1178–1271.  https://doi.org/10.1016/j.pmatsci.2011.03.003CrossRefGoogle Scholar
  47. 47.
    Meyer JC, Geim AK, Katsnelson MI, Novoselov KS, Booth TJ, Roth S (2007) The structure of suspended graphene sheets. Nature 446:60–63CrossRefPubMedGoogle Scholar
  48. 48.
    Hummers WS, Offeman RE (1958) Preparation of graphitic oxide. J Am Chem Soc 80(6): 1339–1339.  https://doi.org/10.1021/ja01539a017CrossRefGoogle Scholar
  49. 49.
    Kim HH, Song DW, Kim MJ, Ryu SJ, Um IC, Ki CS, Park YH (2016) Effect of silk fibroin molecular weight on physical property of silk hydrogel. Polymer 90(Suppl C):26–33.  https://doi.org/10.1016/j.polymer.2016.02.054CrossRefGoogle Scholar
  50. 50.
    Brown J, Lu C-L, Coburn J, Kaplan DL (2015) Impact of silk biomaterial structure on proteolysis. Acta Biomater 11(Suppl C):212–221.  https://doi.org/10.1016/j.actbio.2014.09.013CrossRefPubMedGoogle Scholar
  51. 51.
    Kokubo T, Takadama H (2006) How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 27(15):2907–2915.  https://doi.org/10.1016/j.biomaterials.2006.01.017CrossRefPubMedGoogle Scholar
  52. 52.
    Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR (2006) Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 27(18): 3413–3431.  https://doi.org/10.1016/j.biomaterials.2006.01.039CrossRefPubMedGoogle Scholar
  53. 53.
    Taguchi T, Kishida A, Akashi M (1999) Apatite formation on/in hydrogel matrices using an alternate soaking process: II. Effect of swelling ratios of poly(vinyl alcohol) hydrogel matrices on apatite formation. J Biomater Sci Polym Ed 10(3):331–339CrossRefPubMedGoogle Scholar
  54. 54.
    Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63CrossRefGoogle Scholar
  55. 55.
    Legrand C, Bour JM, Jacob C, Capiaumont J, Martial A, Marc A, Wudtke M, Kretzmer G, Demangel C, Duval D (1992) Lactate dehydrogenase (LDH) activity of the cultured eukaryotic cells as marker of the number of dead cells in the medium [corrected]. J Biotechnol 25(3): 231–243CrossRefPubMedGoogle Scholar
  56. 56.
    Xu S, Yong L, Wu P (2013) One-pot, green, rapid synthesis of flowerlike gold nanoparticles/reduced graphene oxide composite with regenerated silk fibroin as efficient oxygen reduction electrocatalysts. ACS Appl Mater Interfaces 5(3):654–662.  https://doi.org/10.1021/am302076xCrossRefPubMedGoogle Scholar
  57. 57.
    An J, Gou Y, Yang C, Hu F, Wang C (2013) Synthesis of a biocompatible gelatin functionalized graphene nanosheets and its application for drug delivery. Mater Sci Eng C 33(5):2827–2837.  https://doi.org/10.1016/j.msec.2013.03.008CrossRefGoogle Scholar
  58. 58.
    Huang L, Li C, Yuan W, Shi G (2013) Strong composite films with layered structures prepared by casting silk fibroin-graphene oxide hydrogels. Nanoscale 5(9):3780–3786.  https://doi.org/10.1039/c3nr00196bCrossRefPubMedGoogle Scholar
  59. 59.
    Reina A, Jia X, Ho J, Nezich D, Son H, Bulovic V, Dresselhaus MS, Kong J (2009) Large area, few-layer graphene films on arbitrary substrates by chemical vapor deposition. Nano Lett 9(1):30–35.  https://doi.org/10.1021/nl801827vCrossRefPubMedGoogle Scholar
  60. 60.
    Ma X, Li Y, Wang W, Ji Q, Xia Y (2013) Temperature-sensitive poly(N-isopropylacrylamide)/graphene oxide nanocomposite hydrogels by in situ polymerization with improved swelling capability and mechanical behavior. Eur Polym J 49(2):389–396.  https://doi.org/10.1016/j.eurpolymj.2012.10.034CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Bianca Galateanu
    • 1
  • Ariana Hudita
    • 1
  • Catalin Zaharia
    • 2
  • Mihaela-Cristina Bunea
    • 2
  • Eugenia Vasile
    • 2
  • Mihaela-Ramona Buga
    • 3
  • Marieta Costache
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of BucharestBucharestRomania
  2. 2.Advanced Polymer Materials GroupUniversity Politehnica of BucharestBucharestRomania
  3. 3.National Research and Development Institute for Cryogenics and Isotopic TechnologiesRamnicu ValceaRomania

Personalised recommendations