Silk fibroin-based scaffolds for tissue engineering

Abstract

Silk fibroin (SF) from the Bombyx mori silkworm exhibits attractive potential applications as biomechanical materials, due to its unique mechanical and biological properties. This review outlines the structure and properties of SF, including of its biocompatibility and biodegradability. It highlights recent researches on the fabrication of various SF-based composites scaffolds that are promising for tissue engineering applications, and discusses synthetic methods of various SF-based composites scaffolds and valuable approaches for controlling cell behaviors to promote the tissue repair. The function of extracellular matrices and their interaction with cells are also reviewed here.

Keywords

silk fibroin (SF) / scaffold / tissue engineering / biomaterial / tissue repair

References

[1] Sirichaisit J, Young R J, Vollrath F. Molecular deformation in spider dragline silk subjected to stress. Polymer , 2000, 41(3): 1223–1227
[2] Demura M, Asakura T, Kuroo T. Immobilization of biocatalysts with Bombyx mori silk fibroin by several kinds of physical treatment and its application to glucose sensors. Biosensors , 1989, 4(6): 361-372
[3] Lawrence B D, Cronin-Golomb M, Georgakoudi I, . Bioactive silk protein biomaterial systems for optical devices. Biomacromolecules , 2008, 9(4): 1214-1220
[4] Leal-Ega?a A, Scheibel T. Silk-based materials for biomedical applications. Biotechnology and Applied Biochemistry , 2010, 55(3): 155-167
[5] Murphy A R, Kaplan D L. Biomedical applications of chemically-modified silk fibroin. Journal of Materials Chemistry , 2009, 19(36): 6443-6450
[6] Porter D, Vollrath F. Silk as a biomimetic ideal for structural polymers. Advanced Materials , 2009, 21(4): 487-492
[7] Wang Y, Kim H J, Vunjak-Novakovic G, . Stem cell-based tissue engineering with silk biomaterials. Biomaterials , 2006, 27(36): 6064-6082
[8] Wang Y, Blasioli D J, Kim H J, . Cartilage tissue engineering with silk scaffolds and human articular chondrocytes. Biomaterials , 2006, 27(25): 4434-4442
[9] Hofmann S, Wong Po Foo C T, Rossetti F, . Silk fibroin as an organic polymer for controlled drug delivery. Journal of Controlled Release , 2006, 111(1-2): 219-227
[10] Wenk E, Wandrey A J, Merkle H P, . Silk fibroin spheres as a platform for controlled drug delivery. Journal of Controlled Release , 2008, 132(1): 26-34
[11] Chen J, Altman G H, Karageorgiou V, . Human bone marrow stromal cell and ligament fibroblast responses on RGD-modified silk fibers. Journal of Biomedical Materials Research Part A , 2003, 67(2): 559-570
[12] Liivak O, Blye A, Shah N, . A microfabricated wet-spinning apparatus to spin fibers of silk proteins. Structure-property correlations. Macromolecules , 1998, 31(9): 2947-2951
[13] Arai T, Freddi G, Innocenti R, . Biodegradation of Bombyx mori silk fibroin fibers and films. Journal of Applied Polymer Science , 2004, 91(4): 2383-2390
[14] Jin H J, Park J, Karageorgiou V, . Water-stable silk films with reduced β-sheet content. Advanced Functional Materials , 2005, 15(8): 1241-1247
[15] Langer R, Vacanti J P. Tissue engineering. Science , 1993, 260(5110): 920-926
[16] Nerem R M, Sambanis A. Tissue engineering: from biology to biological substitutes. Tissue Engineering , 1995, 1(1): 3-13
[17] Mondal M, Trivedy K, Nirmal K S. The silk proteins, sericin and fibroin in silkworm, Bombyx mori linn.- a review. Caspian Journal of Environmental Sciences , 2007, 5(2): 63-76
[18] Ogawa S, Tomita M, Shimizu K, . Generation of a transgenic silkworm that secretes recombinant proteins in the sericin layer of cocoon: production of recombinant human serum albumin. Journal of Biotechnology , 2007, 128(3): 531-544
[19] Chen X, Shao Z, Knight D P, . Conformation transition kinetics of Bombyx mori silk protein. Proteins: Structure, Function, and Bioinformatics , 2007, 68(1): 223-231
[20] Harris M, Johnson T B. Study of silk fibroin in the dispersed state. Industrial & Engineering Chemistry , 1930, 22(9): 965-967
[21] Harris M, Johnson T B. Study of the fibroin from silk in the isoelectric region. Industrial & Engineering Chemistry , 1930, 22(5): 539-542
[22] Kay L M, Schroeder W A. The chromatographic separation and identification of some peptides in partial hydrolysates of silk fibroin. Journal of the American Chemical Society , 1954, 76(13): 3564-3568
[23] Kay L M, Schroeder W A, Munger N, . The chromatographic separation and identification of some peptides in partial hydrolysates of tussah silk fibroin. Journal of the American Chemical Society , 1956, 78(11): 2430-2434
[24] Schroeder W A, Kay L M, Lewis B, . The amino acid composition of Bombyx mori silk fibroin and of tussah silk fibroin. Journal of the American Chemical Society , 1955, 77(14): 3908-3913
[25] Rousseau M E, Beaulieu L, Lefèvre T, . Characterization by Raman microspectroscopy of the strain-induced conformational transition in fibroin fibers from the silkworm Samia cynthia ricini. Biomacromolecules , 2006, 7(9): 2512-2521
[26] Hu B W, Zhou P, Noda I, . Generalized two-dimensional correlation analysis of NMR and Raman spectra for structural evolution characterizations of silk fibroin. The Journal of Physical Chemistry B , 2006, 110(36): 18046-18051
[27] Hernandez Cruz D, Rousseau M-E, West M M, . Quantitative mapping of the orientation of fibroin β-sheets in B.mori cocoon fibers by scanning transmission X-ray microscopy. Biomacromolecules , 2006, 7(3): 836-843
[28] Tanaka C, Takahashi R, Asano A, . Structural analyses of Anaphe silk fibroin and several model peptides using ¹³C NMR and X-ray diffraction methods. Macromolecules , 2008, 41(3): 796-803
[29] Ha S W, Gracz H S, Tonelli A E, . Structural study of irregular amino acid sequences in the heavy chain of Bombyx mori silk fibroin. Biomacromolecules , 2005, 6(5): 2563-2569
[30] Asakura T, Watanabe Y, Itoh T. NMR of silk fibroin. 3. Assignment of carbonyl carbon resonances and their dependence on sequence and conformation in Bombyx mori silk fibroin using selective isotopic labeling. Macromolecules , 1984, 17(11): 2421-2426
[31] Ohgo K, Bagusat F, Asakura T, . Investigation of structural transition of regenerated silk fibroin aqueous solution by Rheo-NMR spectroscopy. Journal of the American Chemical Society , 2008, 130(12): 4182-4186
[32] Demura M, Minami M, Asakura T, . Structure of Bombyx mori silk fibroin based on solid-state NMR orientational constraints and fiber diffraction unit cell parameters. Journal of the American Chemical Society , 1998, 120(6): 1300-1308
[33] Zhou C Z, Confalonieri F, Jacquet M, . Silk fibroin: structural implications of a remarkable amino acid sequence. Proteins: Structure, Function, and Bioinformatics , 2001, 44(2): 119-122
[34] Heslot H. Artificial fibrous proteins: a review. Biochimie , 1998, 80(1): 19-31
[35] Kratky O, Schauenstein E, Sekora A. An unstable lattice in silk fibroin. Nature , 1950, 165(4191): 319-320
[36] Ambrose E J, Bamford C H, Elliott A, . Water soluble silk: an α-protein. Nature , 1951, 167(4242): 264-265
[37] Carlisle C H, Bernal J D. Crystallography. Annual Reports on the Progress of Chemistry , 1955, 52: 380-403
[38] Kratky O.Zur molekularen morphologie des seidenfibroins. Monatshefte Für Chemie- Chemical Monthly , 1956, 87(2): 269 -280
[39] Warwicker J O. Comparative studies of fibroins. II. The crystal structures of various fibroins. Journal of Molecular Biology , 1960, 2(6): 350-362
[40] Valluzzi R, Gido S P, Zhang W, . Trigonal crystal structure of Bombyx mori silk incorporating a threefold helical chain conformation found at the air-water interface. Macromolecules , 1996, 29(27): 8606-8614
[41] Sohn S, Strey H H, Gido S P. Phase behavior and hydration of silk fibroin. Biomacromolecules , 2004, 5(3): 751-757
[42] Mercer E H. Studies on the soluble proteins of the silk gland of the silkworm, Bombyx mori. Textile Research Journal , 1954, 24(2): 135-145
[43] Lu Q, Feng Q, Hu K, . Preparation of three-dimensional fibroin/collagen scaffolds in various pH conditions. Journal of Materials Science: Materials in Medicine , 2008, 19(2): 629-634
[44] Zhou P, Xie X, Knight D P, . Effects of pH and calcium ions on the conformational transitions in silk fibroin using 2D Raman correlation spectroscopy and 13C solid-state NMR. Biochemistry , 2004, 43(35): 11302-11311
[45] Cunniff P M, Fossey S A, Auerbach M A, . Mechanical and thermal properties of dragline silk from the spider Nephila clavipes. Polymers for Advanced Technologies , 1994, 5(8): 401-410
[46] Pérez-Rigueiro J, Viney C, Llorca J, . Mechanical properties of single-brin silkworm silk. Journal of Applied Polymer Science , 2000, 75(10): 1270-1277
[47] Jiang C, Wang X, Gunawidjaja R, . Mechanical properties of robust ultrathin silk fibroin films. Advanced Functional Materials , 2007, 17(13): 2229-2237
[48] Pins G D, Christiansen D L, Patel R, . Self-assembly of collagen fibers. Influence of fibrillar alignment and decorin on mechanical properties. Biophysical Journal , 1997, 73(4): 2164-2172
[49] Simmons A, Ray E, Jelinski L W. Solid-state 13C NMR of Nephila lavipes dragline silk establishes structure and identity of crystalline regions. Macromolecules , 1994, 27(18): 5235-5237
[50] Parkhe A D, Seeley S K, Gardner K, . Structural studies of spider silk proteins in the fiber. Journal of Molecular Recognition , 1997, 10(1): 1-6
[51] van Beek J D, Hess S, Vollrath F, . The molecular structure of spider dragline silk: folding and orientation of the protein backbone. Proceedings of the National Academy of Sciences of the United States of America , 2002, 99(16): 10266-10271
[52] Giesa T, Arslan M, Pugno N M, . Nanoconfinement of spider silk fibrils begets superior strength, extensibility, and toughness. Nano Letters , 2011, 11(11): 5038-5046
[53] Vollrath F. Spiders’webs. Current Biology , 2005, 15(10): 364-365
[54] Akai H, Nagashima T, Aoyagi S. Ultrastructure of posterior silk gland cells and liquid silk in Indian tasar silkworm, Antheraea ylitta drury (Lepidoptera: Saturniidae). International Journal of Insect Morphology and Embryology , 1993, 22(5): 497-506
[55] Hu K, Cui F, Lv Q, . Preparation of fibroin/recombinant human-like collagen scaffold to promote fibroblasts compatibility. Journal of Biomedical Materials Research Part A , 2008, 84A(2): 483-490
[56] Lv Q, Hu K, Feng Q L, . Growth of fibroblast and vascular smooth muscle cells in fibroin/collagen scaffold. Materials Science and Engineering C , 2009, 29(7): 2239-2245
[57] Fan H, Liu H, Toh S L, . Anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold in large animal model. Biomaterials , 2009, 30(28): 4967-4977
[58] Altman G H, Diaz F, Jakuba C, . Silk-based biomaterials. Biomaterials , 2003, 24(3): 401-416
[59] Peleg H, Rao U N M, Emrich L J. An experimental comparison of suture materials for tracheal and bronchial anastomoses. The Thoracic and Cardiovascular Surgeon , 1986, 34(6): 384-388
[60] Soong H K, Kenyon K R. Adverse reactions to virgin silk sutures in cataract surgery. Ophthalmology , 1984, 91(5): 479-483
[61] Wen C M, Ye S T, Zhou L X, . Silk-induced asthma in children: a report of 64 cases. Annals of Allergy , 1990, 65(5): 375-378
[62] Li X G, Wu L Y, Huang M R, . Conformational transition and liquid crystalline state of regenerated silk fibroin in water. Biopolymers , 2008, 89(6): 497-505
[63] Yang Y, Shao Z, Chen X, . Optical spectroscopy to investigate the structure of regenerated Bombyx ori silk fibroin in solution. Biomacromolecules , 2004, 5(3): 773-779
[64] Zhao C, Wu X, Zhang Q, . Enzymatic degradation of Antheraea ernyi silk fibroin 3D scaffolds and fibers. International Journal of Biological Macromolecules , 2011, 48(2): 249-255
[65] Horan R L, Antle K, Collette A L, . In vitro degradation of silk fibroin. Biomaterials , 2005, 26(17): 3385-3393
[66] Gunatillake P A, Adhikari R. Biodegradable synthetic polymers for tissue engineering. European Cells and Materials , 2003, 5: 1-16
[67] Zhang J-G, Mo X-M. Current research on electrospinning of silk fibroin and its blends with natural and synthetic biodegradable polymers. Frontiers of Materials Science , 2013, 7(2): 129-142
[68] Ren Y J, Zhou Z Y, Liu B F, . Preparation and characterization of fibroin/hyaluronic acid composite scaffold. International Journal of Biological Macromolecules , 2009, 44(4): 372-378
[69] Lun B, Jianmei X, Qilong S, . On the growth model of the capillaries in the porous silk fibroin films. Journal of Materials Science: Materials in Medicine , 2007, 18(10): 1917-1921
[70] Lu Q, Zhang S, Hu K, . Cytocompatibility and blood compatibility of multifunctional fibroin/collagen/heparin scaffolds. Biomaterials , 2007, 28(14): 2306-2313
[71] Lv Q, Hu K, Feng Q, . Preparation and characterization of PLA/fibroin composite and culture of HepG2 (human hepatocellular liver carcinoma cell line) cells. Composites Science and Technology , 2007, 67(14): 3023-3030
[72] Kong X, Sun X, Cui F, . Effect of solute concentration on fibroin regulated biomineralization of calcium phosphate. Materials Science and Engineering C , 2006, 26(4): 639-643
[73] Hu K, Lv Q, Cui F Z, . Biocompatible fibroin blended films with recombinant human-like collagen for hepatic tissue engineering. Journal of Bioactive and Compatible Polymers , 2006, 21(1): 23-37
[74] Lv Q, Hu K, Feng Q L, . Fibroin/collagen hybrid hydrogels with crosslinking method: preparation, properties, and cytocompatibility. Journal of Biomedical Materials Research Part A , 2008, 84A(1): 198-207
[75] O’Connor S M, Andreadis J D, Shaffer K M, . Immobilization of neural cells in three-dimensional matrices for biosensor applications. Biosensors & Bioelectronics , 2000, 14(10-11): 871-881
[76] Vasconcelos A, Freddi G, Cavaco-Paulo A. Biodegradable materials based on silk fibroin and keratin. Biomacromolecules , 2008, 9(4): 1299-1305
[77] Zoccola M, Aluigi A, Vineis C, . Study on cast membranes and electrospun nanofibers made from keratin/fibroin blends. Biomacromolecules , 2008, 9(10): 2819-2825
[78] Yang Y, Ding F, Wu J, . Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration. Biomaterials , 2007, 28(36): 5526-5535
[79] Hofmann S, Hagenmüller H, Koch A M, . Control of in vitro tissue-engineered bone-like structures using human mesenchymal stem cells and porous silk scaffolds. Biomaterials , 2007, 28(6): 1152-1162
[80] Meinel L, Fajardo R, Hofmann S, . Silk implants for the healing of critical size bone defects. Bone , 2005, 37(5): 688-698
[81] Meinel L, Betz O, Fajardo R, . Silk based biomaterials to heal critical sized femur defects. Bone , 2006, 39(4): 922-931
[82] Wang Y, Bella E, Lee C S D, . The synergistic effects of 3-D porous silk fibroin matrix scaffold properties and hydrodynamic environment in cartilage tissue regeneration. Biomaterials , 2010, 31(17): 4672-4681
[83] Wang Y, Kim U J, Blasioli D J, . In vitro cartilage tissue engineering with 3D porous aqueous-derived silk scaffolds and mesenchymal stem cells. Biomaterials , 2005, 26(34): 7082-7094
[84] Liu H, Fan H, Toh S L, . A comparison of rabbit mesenchymal stem cells and anterior cruciate ligament fibroblasts responses on combined silk scaffolds. Biomaterials , 2008, 29(10): 1443-1453
[85] Nakazawa Y, Sato M, Takahashi R, . Development of small-diameter vascular grafts based on silk fibroin fibers from Bombyxmori for vascular regeneration. Journal of Biomaterials Science, Polymer Edition , 2011, 22(1-3): 195-206
[86] Meinel L, Karageorgiou V, Hofmann S, . Engineering bone-like tissue in vitro using human bone marrow stem cells and silk scaffolds. Journal of Biomedical Materials Research Part A , 2004, 71(1): 25-34
[87] Huang W, Begum R, Barber T, . Regenerative potential of silk conduits in repair of peripheral nerve injury in adult rats. Biomaterials , 2012, 33(1): 59-71
[88] Wei Y, Gong K, Zheng Z, . Chitosan/silk fibroin-based tissue-engineered graft seeded with adipose-derived stem cells enhances nerve regeneration in a rat model. Journal of Materials Science: Materials in Medicine , 2011, 22(8): 1947-1964
[89] Silva S S, Motta A, Rodrigues M T, . Novel genipin-cross-linked chitosan/silk fibroin sponges for cartilage engineering strategies. Biomacromolecules , 2008, 9(10): 2764-2774
[90] Roh D H, Kang S Y, Kim J Y, . Wound healing effect of silk fibroin/alginate-blended sponge in full thickness skin defect of rat. Journal of Materials Science: Materials in Medicine , 2006, 17(6): 547-552
[91] Yang M C, Chi N H, Chou N K, . The influence of rat mesenchymal stem cell CD44 surface markers on cell growth, fibronectin expression, and cardiomyogenic differentiation on silk fibroin - Hyaluronic acid cardiac patches. Biomaterials , 2010, 31(5): 854-862
[92] Rusa C C, Bridges C, Ha S-W, . Conformational changes induced in Bombyx mori silk fibroin by cyclodextrin inclusion complexation. Macromolecules , 2005, 38(13): 5640-5646
[93] Zhang X, Baughman C B, Kaplan D L. In vitro evaluation of electrospun silk fibroin scaffolds for vascular cell growth. Biomaterials , 2008, 29(14): 2217-2227
[94] Zhang X, Wang X, Keshav V, . Dynamic culture conditions to generate silk-based tissue-engineered vascular grafts. Biomaterials , 2009, 30(19): 3213-3223
[95] Jin H J, Park J, Valluzzi R, . Biomaterial films of Bombyx mori silk fibroin with poly(ethylene oxide). Biomacromolecules , 2004, 5(3): 711-717
[96] Li C, Vepari C, Jin H J, . Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials , 2006, 27(16): 3115-3124
[97] Wang C Y, Zhang K H, Fan C Y, . Aligned natural-synthetic polyblend nanofibers for peripheral nerve regeneration. Acta Biomaterialia , 2011, 7(2): 634-643
[98] Sahoo S, Toh S L, Goh J C H. A bFGF-releasing silk/PLGA-based biohybrid scaffold for ligament/tendon tissue engineering using mesenchymal progenitor cells. Biomaterials , 2010, 31(11): 2990-2998
[99] Bray L J, George K A, Ainscough S L, . Human corneal epithelial equivalents constructed on Bombyx mori silk fibroin membranes. Biomaterials , 2011, 32(22): 5086-5091
[100] Gil E S, Hudson S M. Effect of silk fibroin interpenetrating networks on swelling/deswelling kinetics and rheological properties of poly(N-isopropylacrylamide) hydrogels. Biomacromolecules , 2007, 8(1): 258-264
[101] Kweon H, Ha H C, Um I C, . Physical properties of silk fibroin/chitosan blend films. Journal of Applied Polymer Science , 2001, 80(7): 928-934
[102] Altman A M, Yan Y, Matthias N, . Human adipose-derived stem cells seeded on a silk fibroin-chitosan scaffold enhance wound repair in a murine soft tissue injury model. Stem Cells , 2009, 27(1): 250-258
[103] Foss C, Merzari E, Migliaresi C, . Silk fibroin/hyaluronic acid 3D matrices for cartilage tissue engineering. Biomacromolecules , 2013, 14(1): 38-47
[104] Whitesides G M, Wong A P. The intersection of biology and materials science. MRS Bulletin , 2006, 31(1): 19-27
[105] Hu K, Lv Q, Cui F Z, . A novel poly (L-lactide) (PLLA)/fibroin hybrid scaffold to promote hepatocyte viability and decrease macrophage responses. Journal of Bioactive and Compatible Polymers , 2007, 22(4): 395-410