Silk Fibroin and Spidroin Bioengineering Constructions for Regenerative Medicine and Tissue Engineering (Review)

The review is about the developments of modern bioengineering constructs from two unique biopolymers: the main protein of silkworm silk, fibroin, and frame silk of spider web, spidroin, and their applications in regenerative medicine and tissue engineering. Both types of polymers possess such important properties as biocompatibility, biodegradability, high strength and elasticity. Availability of silkworm cocoons in nature, debugged methods of fibroin purification make this protein very perspective in bioengineering constructs. A spider web protein, spidroin, is less common in nature, but the development of alternative methods for its production makes it a promising biopolymer.

The structure and properties of silk fibroin and spidroin, their advantages over other natural and synthetic polymers, technologies of biopolymer construct fabrication are considered in this review. Silk fibroin and spidroin are shown to be applied for creation of 3D matrices promoting regeneration of damaged organs and tissues, biodegradable cell carriers and pharmaceutical preparations.

1. Jeffries E.M., Allen R.A., Gao J., Pesce M., Wang Y. Highly elastic and suturable electrospun poly(glycerol sebacate) fibrous scaffolds. Acta Biomater 2015; 18: 30–39, https://doi.org/10.1016/j.actbio.2015.02.005.
2. Lace R., Murray-Dunning C., Williams R. Biomaterials for ocular reconstruction. J Mater Sci 2015; 50(4): 1523–1534, https://doi.org/10.1007/s10853-014-8707-0.
3. Song Z., Shi B., Ding J., Zhuang X., Zhang X., Fu C., Chen X. Prevention of postoperative tendon adhesion by biodegradable electrospun membrane of poly(lactide-co-glycolide). Chinese Journal of Polymer Science 2015; 33(4): 587–596, https://doi.org/10.1007/s10118-015-1611-5.
4. Wadbua P., Promdonkoy B., Maensiri S., Siri S. Different properties of electrospun fibrous scaffolds of separated heavy-chain and light-chain fibroins of Bombyx mori. Int J Biol Macromol 2010; 46(5): 493–501, https://doi.org/10.1016/j.ijbiomac.2010.03.007.
5. Ho W. Single-molecule chemistry. J Chem Phys 2002; 117(24): 11033–11061, https://doi.org/10.1063/1.1521153.
6. Tanaka K., Inoue S., Mizuno S. 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 1999; 29(3): 269–276, https://doi.org/10.1016/s0965-1748(98)00135-0.
7. Inoue S., Tanaka K., Arisaka F., Kimura S., Ohtomo K., Mizuno S. Silk fibroin of Bombyx mori is secreted, assembling a high molecular mass elementary unit consisting of H-chain, L-chain, and P25, with a 6:6:1 molar ratio. J Biol Chem 2000; 275(51): 40517–40528, https://doi.org/10.1074/jbc.m006897200.
8. Vepari C., Kaplan D.L. Silk as a biomaterial. Prog Polym Sci 2007; 32(8–9): 991–1007, https://doi.org/10.1016/j.progpolymsci.2007.05.013.
9. Lucas F., Shaw J.T., Smith S.G. The amino acid sequence in a fraction of the fibroin of Bombyx mori. Biochem J 1957; 66(3): 468–479, https://doi.org/10.1042/bj0660468.
10. Gholami A., Tavanai H., Moradi A.R. Production of fibroin nanopowder through electrospraying. J Nanopart Res 2011; 13(5): 2089–2098, https://doi.org/10.1007/s11051-010-9965-7.
11. Scherer M.P., Frank G., Gummer A.W. Experimental determination of the mechanical impedance of atomic force microscopy cantilevers in fluids up to 70 kHz. J Appl Phys 2000; 88(5): 2912–2920, https://doi.org/10.1063/1.1287522.
12. Dong Y., Dai F., Ren Y., Liu H., Chen L., Yang P., Liu Y., Li X., Wang W., Xiang H. Comparative transcriptome analyses on silk glands of six silkmoths imply the genetic basis of silk structure and coloration. BMC Genomics 2015; 16(1), https://doi.org/10.1186/s12864-015-1420-9.
13. Kim E.Y., Tripathy N., Park J.Y., Lee S.E., Joo C.-K., Khang G. Silk fibroin film as an efficient carrier for corneal endothelial cells regeneration. Macromolecular Research 2015; 23(2): 189–195, https://doi.org/10.1007/s13233-015-3027-z.
14. Smith R.K., Lewis P.A., Weiss P.S. Patterning self-assembled monolayers. Progress in Surface Science 2004; 75(1–2): 1–68, https://doi.org/10.1016/j.progsurf.2003.12.001.
15. Sun K., Li H., Li R., Nian Z., Li D., Xu C. Silk fibroin/collagen and silk fibroin/chitosan blended three-dimensional scaffolds for tissue engineering. Eur J Orthop Surg Traumatol 2015; 25(2): 243–249, https://doi.org/10.1007/s00590-014-1515-z.
16. Nakazawa Y., Sato M., Takahashi R., Aytemiz D., Takabayashi C., Tamura T., Enomoto S., Sata M., Asakura T. Development of small-diameter vascular grafts based on silk fibroin fibers from Bombyx mori for vascular regeneration. J Biomater Sci Polym Ed 2011; 22(1–3): 195–206, https://doi.org/10.1163/092050609x12586381656530.
17. Lian X.-J., Wang S., Zhu H.-S. Surface properties and cytocompatibillity of silk fibroin films cast from aqueous solutions in different concentrations. Front Mater Sci China 2010; 4(1): 57–63, https://doi.org/10.1007/s11706-010-0013-4.
18. Wang P., Pi B., Wang J.-N., Zhu X.-S., Yang H.-L. Preparation and properties of calcium sulfate bone cement incorporated with silk fibroin and Sema3A-loaded chitosan microspheres. Front Mater Sci 2015; 9(1): 51–65, https://doi.org/10.1007/s11706-015-0278-8.
19. Wenk E., Wandrey A.J., Merkle H.P., Meinel L. Silk fibroin spheres as a platform for controlled drug delivery. J Control Release 2008; 132(1): 26–34, https://doi.org/10.1016/j.jconrel.2008.08.005.
20. Abdel-Fattah W.I., Atwa N., Ali G.W. Influence of the protocol of fibroin extraction on the antibiotic activities of the constructed composites. Prog Biomater 2015; 4(2–4): 77–88, https://doi.org/10.1007/s40204-015-0039-x.
21. Shen Z.Q., Hu J., Wang J.L., Zhou Y.X. Comparison of polycaprolactone and starch/polycaprolactone blends as carbon source for biological denitrification. Int J Environ Sci Technol 2015; 12(4): 1235–1242, https://doi.org/10.1007/s13762-013-0481-z.
22. Vehoff T., Glisović A., Schollmeyer H., Zippelius A., Salditt T. Mechanical properties of spider dragline silk: humidity, hysteresis, and relaxation. Biophys J 2007; 93(12): 4425–4432, https://doi.org/10.1529/biophysj.106.099309.
23. Kluge J.A., Rabotyagova O., Leisk G.G., Kaplan D.L. Spider silks and their applications. Trends Biotechnol 2008; 26(5): 244–251, https://doi.org/10.1016/j.tibtech.2008.02.006.
24. Sponner A., Schlott B., Vollrath F., Unger E., Grosse F., Weisshart K. Characterization of the protein components of Nephila clavipes dragline silk. Biochemistry 2005; 44(12): 4727–4736, https://doi.org/10.1021/bi047671k.
25. van Beek J.D., Hess S., Vollrath F., Meier B.H. The molecular structure of spider dragline silk: folding and orientation of the protein backbone. Proc Natl Acad Sci USA 2002; 99(16): 10266–10271, https://doi.org/10.1073/pnas.152162299.
26. Rousseau M.-E., Lefèvre T., Pézolet M. Conformation and orientation of proteins in various types of silk fibers produced by Nephila clavipes spiders. Biomacromolecules 2009; 10(10): 2945–2953, https://doi.org/10.1021/bm9007919.
27. Simmons A.H., Michal C.A., Jelinski L.W. Molecular orientation and two-component nature of the crystalline fraction of spider dragline silk. Science 1996; 271(5245): 84–87, https://doi.org/10.1126/science.271.5245.84.
28. Thiel B.L., Guess K.B., Viney C. Non-periodic lattice crystals in the hierarchical microstructure of spider (major ampullate) silk. Biopolymers 1997; 41(7): 703–719, https://doi.org/10.1002/(sici)1097-0282(199706)41:7703::aid-bip13.0.co;2-t.
29. Cunniff P.M., Fossey S.A., Auerbach M.A., Song J.W., Kaplan D.L., Adams W.W., Eby R.K., Mahoney D., Vezie D.L. Mechanical and thermal properties of dragline silk from the spider Nephila clavipes. Polym Adv Technol 1994; 5(8): 401–410, https://doi.org/10.1002/pat.1994.220050801.
30. Agnarsson I., Boutry C., Blackledge T.A. Spider silk aging: initial improvement in a high performance material followed by slow degradation. J Exp Zool A Ecol Genet Physiol 2008; 309(8): 494–504, https://doi.org/10.1002/jez.480.
31. Osaki S., Yamamoto K., Kajiwara A., Murata M. Evaluation of the Resistance of Spider Silk to Ultraviolet Irradiation. Polymer Journal 2004; 36(8): 623–627, https://doi.org/10.1295/polymj.36.623.
32. Sapede D., Seydel T., Forsyth V.T., Koza M.M., Schweins R., Vollrath F., Riekel C. Nanofibrillar structure and molecular mobility in spider dragline silk. Macromolecules 2005; 38(20): 8447–8453, https://doi.org/10.1021/ma0507995.
33. Yang J., Barr L.A., Fahnestock S.R., Liu Z.-B. High yield recombinant silk-like protein production in transgenic plants through protein targeting. Transgenic Res 2005; 14(3): 313–324, https://doi.org/10.1007/s11248-005-0272-5.
34. Scheller J., Henggeler D., Viviani A., Conrad U. Purification of spider silk-elastin from transgenic plants and application for human chondrocyte proliferation. Transgenic Res 2004; 13(1): 51–57, https://doi.org/10.1023/b:trag.0000017175.78809.7a.
35. Wen H., Lan X., Zhang Y., Zhao T., Wang Y., Kajiura Z., Nakagaki M. Transgenic silkworms (Bombyx mori) produce recombinant spider dragline silk in cocoons. Mol Biol Rep 2010; 37(4): 1815–1821, https://doi.org/10.1007/s11033-009-9615-2.
36. Slotta U., Tammer M., Kremer F., Koelsch P., Scheibel T. Structural analysis of spider silk films. Supramolecular Chemistry 2006; 18(5): 465–471, https://doi.org/10.1080/10610270600832042.
37. Lazaris A., Arcidiacono S., Huang Y., Zhou J.F., Duguay F., Chretien N., Welsh E.A., Soares J.W., Karatzas C.N. Spider silk fibers spun from soluble recombinant silk produced in mammalian cells. Science 2002; 295(5554): 472–476, https://doi.org/10.1126/science.1065780.
38. Grip S., Johansson J., Hedhammar M. Engineered disulfides improve mechanical properties of recombinant spider silk. Protein Sci 2009; 18(5): 1012–1022, https://doi.org/10.1002/pro.111.
39. Rabotyagova O.S., Cebe P., Kaplan D.L. Self-assembly of genetically engineered spider silk block copolymers. Biomacromolecules 2009; 10(2): 229–236, https://doi.org/10.1021/bm800930x.
40. Hauptmann V., Menzel M., Weichert N., Reimers K., Spohn U., Conrad U. In planta production of ELPylated spidroin-based proteins results in non-cytotoxic biopolymers. BMC Biotechnol 2015; 15(1): 9, https://doi.org/10.1186/s12896-015-0123-2.
41. Zhu G.C., Gu Y.Q., Geng X., Feng Z.G., Zhang S.W., Ye L., Wang Z.G. Experimental study on the construction of small three-dimensional tissue engineered grafts of electrospun poly-epsilon-caprolactone. Journal of materials science. J Mater Sci Mater Med 2015; 26(2): 112, https://doi.org/10.1007/s10856-015-5448-9.
42. Costa M.P., Teixeira N.H., Longo M.V., Gemperli R., Costa H.J. Combined polyglycolic acid tube and autografting versus autografting or polyglycolic acid tube alone. A comparative study of peripheral nerve regeneration in rats. Acta Cir Bras 2015; 30(1): 46–53, https://doi.org/10.1590/s0102-86502015001000006.
43. Cartmill B.T., Parham D.M., Strike P.W., Griffiths L., Parkin B. How do absorbable sutures absorb? A prospective double-blind randomized clinical study of tissue reaction to polyglactin 910 sutures in human skin. Orbit 2014; 33(6): 437–443, https://doi.org/10.3109/01676830.2014.950285.
44. Pihlajamäki H., Tynninen O., Karjalainen P., Rokkanen P. The impact of polyglycolide membrane on a tendon after surgical rejoining. A histological and histomorphometric analysis in rabbits. J Biomed Mater Res A 2007; 81(4): 987–993, https://doi.org/10.1002/jbm.a.31144.
45. Zhu Y., Liang C., Bo Y., Xu S. Non-isothermal crystallization behavior of compatibilized polypropylene/recycled polyethylene terephthalate blends. J Therm Anal Calorim 2015; 119(3): 2005–2013, https://doi.org/10.1007/s10973-014-4349-3.
46. Makarawo T.P., Reynolds R.A., Cullen M.L. Polylactide bioabsorbable struts for chest wall reconstruction in a pediatric patient. Ann Thorac Surg 2015; 99(2): 689–691, https://doi.org/10.1016/j.athoracsur.2014.03.052.
47. Water J.J., Bohr A., Boetker J., Aho J., Sandler N., Nielsen H.M., Rantanen J. Three-dimensional printing of drug-eluting implants: preparation of an antimicrobial polylactide feedstock material. J Pharm Sci 2015; 104(3): 1099–1107, https://doi.org/10.1002/jps.24305.
48. Guo S.Z., Heuzey M.C., Therriault D. Properties of polylactide inks for solvent-cast printing of three-dimensional freeform microstructures. Langmuir 2014; 30(4): 1142–1150, https://doi.org/10.1021/la4036425.
49. de Mel A., Yap T., Cittadella G., Hale L.R., Maghsoudlou P., de Coppi P., Birchall M.A., Seifalian A.M. A potential platform for developing 3D tubular scaffolds for paediatric organ development. J Mater Sci Mater Med 2015; 26(3): 141, https://doi.org/10.1007/s10856-015-5477-4.
50. Alhusein N., Blagbrough I.S., De Bank P.A. Electrospun matrices for localised controlled drug delivery: release of tetracycline hydrochloride from layers of polycaprolactone and poly(ethylene-co-vinyl acetate). Drug Deliv Transl Res 2012; 2(6): 477–488, https://doi.org/10.1007/s13346-012-0106-y.
51. Osten K.M., Aluthge D.C., Mehrkhodavandi P. The effect of steric changes on the isoselectivity of dinuclear indium catalysts for lactide polymerization. Dalton Trans 2015; 44(13): 6126–6139, https://doi.org/10.1039/c5dt00222b.
52. Kim J.A., Van Abel D. Neocollagenesis in human tissue injected with a polycaprolactone-based dermal filler. J Cosmet Laser Ther 2015; 17(2): 99–101, https://doi.org/10.3109/14764172.2014.968586.
53. Xu Z., Zhu J., Liao X., Ni H. Thermal behavior of poly (ethylene terephthalate)/SiO2/TiO2 nano composites prepared via in situ polymerization. J Iran Chem Soc 2014; 12(5): 765–770, https://doi.org/10.1007/s13738-014-0536-1.
54. Mallick B. Analysis of strain-induced crystallinity in neutron-irradiated amorphous PET fiber. Appl Phys A 2015; 119(2): 653–657, https://doi.org/10.1007/s00339-015-9009-3.
55. Ma Z., Kotaki M., Yong T., He W., Ramakrishna S. Surface engineering of electrospun polyethylene terephthalate (PET) nanofibers towards development of a new material for blood vessel engineering. Biomaterials 2005; 26(15): 2527–2536, https://doi.org/10.1016/j.biomaterials.2004.07.026.
56. Huang Z., Bi L., Zhang Z., Han Y. Effects of dimethylolpropionic acid modification on the characteristics of polyethylene terephthalate fibers. Mol Med Rep 2012; 6(4): 709–715, https://doi.org/10.3892/mmr.2012.1012.
57. Ebadi H., Mehdipour-Ataei S. Heat-resistant, pyridine-based polyamides containing ether and ester units with improved solubility. Chinese Journal of Polymer Science 2010; 28(1): 29–37, https://doi.org/10.1007/s10118-010-8212-0.
58. Surguchenko V.A., Ponomareva A.S., Kirsanova L.A., Skaleckij N.N., Sevastianov V.I. The cell-engineered construct of cartilage on the basis of biopolymer hydrogel matrix and human adipose tissue-derived mesenchymal stromal cells (in vitro study). J Biomed Mater Res A 2015; 103(2): 463–470, https://doi.org/10.1002/jbm.a.35197.
59. Sevastianov V.I., Dukhina G.A., Grigoriev A.M., Perova N.V., Kirsanova L.A., Skaletskiy N.N., Akhaladze D.G., Gautier S.V. The functional effectiveness of a cell-engineered construct for the regeneration of articular cartilage. Russian Journal of Transplantology and Artificial Organs 2015; 17(1): 86–96, https://doi.org/10.15825/1995-1191-2015-1-86-96.
60. Srisuwan Y., Srihanam P., Baimark Y. Preparation of silk fibroin microspheres and its application to protein adsorption. Journal of Macromolecular Science, Part A 2009; 46(5): 521–525, https://doi.org/10.1080/10601320902797780.
61. Baimark Y., Srihanam P. Effect of methanol treatment on regenerated silk fibroin microparticles prepared by the emulsification-diffusion technique. Journal of Applied Sciences 2009; 9(21): 3876–3881, https://doi.org/10.3923/jas.2009.3876.3881.
62. Medalia O., Weber I., Frangakis A.S., Nicastro D., Gerisch G., Baumeister W. Macromolecular architecture in eukaryotic cells visualized by cryoelectron tomography. Science 2002; 298(5596): 1209–1213, https://doi.org/10.1126/science.1076184.
63. Jalilian S., Yeganeh H. Preparation and properties of biodegradable polyurethane networks from carbonated soybean oil. Polym Bull 2015; 72(6): 1379–1392, https://doi.org/10.1007/s00289-015-1342-3.
64. Schüttler K.F., Pöttgen S., Getgood A., Rominger M.B., Fuchs-Winkelmann S., Roessler P.P., Ziring E., Efe T. Improvement in outcomes after implantation of a novel polyurethane meniscal scaffold for the treatment of medial meniscus deficiency. Knee Surg Sports Traumatol Arthrosc 2015; 23(7): 1929–1935, https://doi.org/10.1007/s00167-014-2977-6.
65. Breslauer D.N., Muller S.J., Lee L.P. Generation of monodisperse silk microspheres prepared with microfluidics. Biomacromolecules 2010; 11(3): 643–647, https://doi.org/10.1021/bm901209u.
66. Skorotetcky M.S., Borshchev O.V., Surin N.M., Meshkov I.B., Muzafarov A.M., Ponomarenko S.A. Novel cross-linked luminescent silicone composites based on reactive nanostructured organosilicon luminophores. Silicon 2015; 7(2): 191–200, https://doi.org/10.1007/s12633-014-9256-5.
67. Surovikin Y.V., Likholobov V.A. Synthesis and properties of a new generation of carbon materials from the Sibunit family modified with silicon compounds. Solid Fuel Chem 2014; 48(6): 335–348, https://doi.org/10.3103/s036152191406007x.
68. Bouchet-Marquis C., Hoenger A. Cryo-electron tomography on vitrified sections: a critical analysis of benefits and limitations for structural cell biology. Micron 2011; 42(2): 152–162, https://doi.org/10.1016/j.micron.2010.07.003.
69. Liu Q., Shao L., Fan H., Long Y., Zhao N., Yang S., Zhang X., Xu J. Characterization of maxillofacial silicone elastomer reinforced with different hollow microspheres. J Mater Sci 2015; 50(11): 3976–3983, https://doi.org/10.1007/s10853-015-8953-9.
70. Zolotareva N., Semenov V. Microchannel thermocured silicone rubber. Silicon 2015; 7(2): 89–93, https://doi.org/10.1007/s12633-014-9240-0.
71. Lonys L., Vanhoestenberghe A., Julémont N., Godet S., Delplancke M.P., Mathys P., Nonclercq A. Silicone rubber encapsulation for an endoscopically implantable gastrostimulator. Med Biol Eng Comput 2015; 53(4): 319–329, https://doi.org/10.1007/s11517-014-1236-9.
72. Dawson J., Schussler O., Al-Madhoun A., Menard C., Ruel M., Skerjanc I.S. Collagen scaffolds with or without the addition of RGD peptides support cardiomyogenesis after aggregation of mouse embryonic stem cells. In Vitro Cell Dev Biol Anim 2011; 47(9): 653–664, https://doi.org/10.1007/s11626-011-9453-0.
73. Chaisri P., Chingsungnoen A., Siri S. Repetitive Gly-Leu-Lys-Gly-Glu-Asn-Arg-Gly-Asp peptide derived from collagen and fibronectin for improving cell-scaffold interaction. Appl Biochem Biotechnol 2015; 175(5): 2489–2500, https://doi.org/10.1007/s12010-014-1388-y.
74. Kretzschmar M., Bieri O., Miska M., Wiewiorski M., Hainc N., Valderrabano V., Studler U. Characterization of the collagen component of cartilage repair tissue of the talus with quantitative MRI: comparison of T2 relaxation time measurements with a diffusion-weighted double-echo steady-state sequence (dwDESS). Eur Radiol 2015; 25(4): 980–986, https://doi.org/10.1007/s00330-014-3490-5.
75. Mochalov K.E., Efimov A.E., Bobrovsky A., Agapov I.I., Chistyakov A.A., Oleinikov V., Sukhanova A., Nabiev I. Combined scanning probe nanotomography and optical microspectroscopy: a correlative technique for 3D characterization of nanomaterials.. ACS Nano 2013; 7(10): 8953–8962, https://doi.org/10.1021/nn403448p.
76. Togo S., Sato T., Sugiura H., Wang X., Basma H., Nelson A., Liu X., Bargar T.W., Sharp J.G., Rennard S.I. Differentiation of embryonic stem cells into fibroblast-like cells in three-dimensional type I collagen gel cultures. In Vitro Cell Dev Biol Anim 2011; 47(2): 114–124, https://doi.org/10.1007/s11626-010-9367-2.
77. Werkmeister J.A., Edwards G.A., Ramshaw J.A.M. Collagen-based vascular prostheses. In: Biomaterials engineering and devices: human applications. Humana Press; 2000; p. 121–136, http://dx.doi.org/10.1385/1-59259-196-5:121.
78. Bhat SV. Cardiovascular implants and extracorporeal devices. In: Biomaterials. Springer Netherland; 2002; p. 130–162, https://doi.org/10.1007/978-94-010-0328-5_9.
79. Tran A., Brown S., Rosenberg J., Hovsepian D. Tract embolization with gelatin sponge slurry for prevention of pneumothorax after percutaneous computed tomography-guided lung biopsy. Cardiovasc Intervent Radiol 2014; 37(6): 1546–1553, https://doi.org/10.1007/s00270-013-0823-8.
80. Chiu C.-H., Shih H.-C., Jwo S.-C., Hsieh M.-F. Effect of crosslinkers on physical properties of gelatin hollow tubes for tissue engineering application. In: World Congress on Medical Physics and Biomedical Engineering. September 7–12, 2009, Munich, Germany. Springer Berlin Heidelberg; 2009; p. 293–296, https://doi.org/10.1007/978-3-642-03900-3_85.
81. Chou K.F., Chiu H.S., Lin J.H., Huang W.Y., Chen P.Y., Xiao W.L., Chen T.K., Wang L.W. The effect of microwave treatment on the drug release property of gelatin microspheres. In: The 15th International Conference on Biomedical Engineering. Springer International Publishing; 2014; p. 726–729, http://dx.doi.org/10.1007/978-3-319-02913-9_185.
82. Tretenichenko E.M., Datsun V.M., Ignatyuk L.N., Nud’ga L.A. Preparation and properties of chitin and chitosan from a hydroid polyp. Russ J Appl Chem 2006; 79(8): 1341–1346, https://doi.org/10.1134/s1070427206080258.
83. Kaya M., Akata I., Baran T., Menteş A. Physicochemical properties of chitin and chitosan produced from medicinal fungus (Fomitopsis pinicola). Food Biophysics 2015; 10(2): 162–168, https://doi.org/10.1007/s11483-014-9378-8.
84. Bashash S., Saeidpourazar R., Jalili N. Development, analysis and control of a high-speed laser-free atomic force microscope. Rev Sci Instrum 2010; 81(2): 023707, https://doi.org/10.1063/1.3302553.
85. Bhattarai N., Gunn J., Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev 2010; 62(1): 83–99, https://doi.org/10.1016/j.addr.2009.07.019.
86. Pradines B., Bories C., Vauthier C., Ponchel G., Loiseau P.M., Bouchemal K. Drug-free chitosan coated poly(isobutylcyanoacrylate) nanoparticles are active against trichomonas vaginalis and non-toxic towards pig vaginal mucosa. Pharm Res 2015; 32(4): 1229–1236, https://doi.org/10.1007/s11095-014-1528-7.
87. Abou Taleb M.F., Alkahtani A., Mohamed S.K. Radiation synthesis and characterization of sodium alginate/chitosan/hydroxyapatite nanocomposite hydrogels: a drug delivery system for liver cancer. Polym Bull 2015; 72(4): 725–742, https://doi.org/10.1007/s00289-015-1301-z.
88. Grigoriadi K., Giannakas A., Ladavos A.K., Barkoula N.-M. Interplay between processing and performance in chitosan-based clay nanocomposite films. Polym Bull 2015; 72(5): 1145–1161, https://doi.org/10.1007/s00289-015-1329-0.
89. Teterina A.Y., Fedotov A.Y., Egorov A.A., Barinov S.M., Komlev V.S. Microstructure formation in porous calcium phosphate-chitosan bone cements. Inorg Mater 2015; 51(4): 396–399, https://doi.org/10.1134/s0020168515040172.
90. Vioque A. Transformation of cyanobacteria. In: Transgenic microalgae as green cell factories. Springer New York; 2007; p. 12–22, https://doi.org/10.1007/978-0-387-75532-8_2.
91. Beltrán F.J.E., Muñoz-Saldaña J., Torres-Torres D., Torres-Martínez R., Schneider G.A. Atomic force microscopy cantilever simulation by finite element methods for quantitative atomic force acoustic microscopy measurements. Journal of Materials Research 2006; 21(12): 3072–3079, https://doi.org/10.1557/jmr.2006.0379.
92. He Y.X., Zhang N.N., Li W.F., Jia N., Chen B.Y., Zhou K., Zhang J., Chen Y., Zhou C.Z. N-terminal domain of Bombyx mori fibroin mediates the assembly of silk in response to pH decrease. J Mol Biol 2012; 418(3–4): 197–207, https://doi.org/10.1016/j.jmb.2012.02.040.
93. Al-Zoreky N., Al-Otaibi M. Suitability of camel milk for making yogurt. Food Sci Biotechnol 2015; 24(2): 601–606, https://doi.org/10.1007/s10068-015-0078-z.
94. Shibukawa Y., Sato M., Kimura M., Sobhan U., Shimada M., Nishiyama A., Kawaguchi A., Soya M., Kuroda H., Katakura A., Ichinohe T., Tazaki M. Odontoblasts as sensory receptors: transient receptor potential channels, pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction. Pflugers Arch 2015; 467(4): 843–863, https://doi.org/10.1007/s00424-014-1551-x.
95. Zhang X.-Z., Tian F.-J., Hou Y.-M., Ou Z.-H. Preparation and in vitro in vivo characterization of polyelectrolyte alginate–chitosan complex based microspheres loaded with verapamil hydrochloride for improved oral drug delivery. J Incl Phenom Macrocycl Chem 2015; 81(3–4): 429–440, https://doi.org/10.1007/s10847-014-0471-x.
96. Perets A., Baruch Y., Weisbuch F., Shoshany G., Neufeld G., Cohen S. Enhancing the vascularization of three-dimensional porous alginate scaffolds by incorporating controlled release basic fibroblast growth factor microspheres. J Biomed Mater Res A 2003; 65(4): 489–497, https://doi.org/10.1002/jbm.a.10542.
97. Qiao P.-y., Li F.-f., Dong L.-m., Xu T., Xie Q.-f. Delivering MC3T3-E1 cells into injectable calcium phosphate cement through alginate-chitosan microcapsules for bone tissue engineering. J Zhejiang Univ Sci B 2014; 15(4): 382–392, https://doi.org/10.1631/jzus.b1300132.
98. Heywood H.K., Sembi P.K., Lee D.A., Bader D.L. Cellular utilization determines viability and matrix distribution profiles in chondrocyte-seeded alginate constructs. Tissue Eng 2004; 10(9–10): 1467–1479, https://doi.org/10.1089/ten.2004.10.1467.
99. Agapova O.I., Druzhinina T.V., Trofimov K.V., Sevastianov V.I., Agapov I.I. Biodegradable porous scaffolds for the bone tissue regeneration. Inorg Mater Appl Res 2016; 7(2): 219–225, https://doi.org/10.1134/s2075113316020027.
100. Safonova L.А., Bobrova М.М., Agapova О.I., Kotliarova М.S., Arkhipova А.Yu., Moisenovich М.М., Agapov I.I. Biological properties of regenerated silk fibroin films. Sovremennye tehnologii v medicine 2015; 7(3): 6–13, https://doi.org/10.17691/stm2015.7.3.01.
101. Efimov A.E., Agapova O.I., Mochalov K.E., Agapov I.I. Three-dimensional analysis of nanomaterials by scanning probe nanotomography. Physics Procedia 2015; 73: 173–176, https://doi.org/10.1016/j.phpro.2015.09.149.
102. Agapova O.I., Efimov A.E., Moisenovich M.M., Bogush V.G., Agapov I.I. Comparative analysis of three-dimensional nanostructure of porous biocompatible scaffolds made of recombinant spidroin and silk fibroin for regenerative medicine. Russian Journal of Transplantology and Artificial Organs 2015; 17(2): 37, http://dx.doi.org/10.15825/1995-1191-2015-2-37-44.
103. Hou Q., Grijpma D.W., Feijen J. Porous polymeric structures for tissue engineering prepared by a coagulation, compression moulding and salt leaching technique. Biomaterials 2003; 24(11): 1937–1947, https://doi.org/10.1016/s0142-9612(02)00562-8.
104. Moore M.J., Jabbari E., Ritman E.L., Lu L., Currier B.L., Windebank A.J., Yaszemski M.J. Quantitative analysis of interconnectivity of porous biodegradable scaffolds with micro-computed tomography. J Biomed Mater Res A 2004; 71(2): 258–267, https://doi.org/10.1002/jbm.a.30138.
105. Mandal B.B., Kundu S.C. Cell proliferation and migration in silk fibroin 3D scaffolds. Biomaterials 2009; 30(15): 2956–2965, https://doi.org/10.1016/j.biomaterials.2009.02.006.
106. Haugh M.G., Murphy C.M., O’Brien F.J. Novel freeze-drying methods to produce a range of collagen-glycosaminoglycan scaffolds with tailored mean pore sizes. Tissue Eng Part C Methods 2010; 16(5): 887–894, https://doi.org/10.1089/ten.tec.2009.0422.
107. Altman G.H., Diaz F., Jakuba C., Calabro T., Horan R.L., Chen J., Lu H., Richmond J., Kaplan D.L. Silk-based biomaterials. Biomaterials 2003; 24(3): 401–416, https://doi.org/10.1016/s0142-9612(02)00353-8.
108. Zarkoob S., Eby R.K., Reneker D.H., Hudson S.D., Ertley D., Adams W.W. Structure and morphology of electrospun silk nanofibers. Polymer 2004; 45(11): 3973–3977, https://doi.org/10.1016/j.polymer.2003.10.102.
109. Matthews J.A., Wnek G.E., Simpson D.G., Bowlin G.L. Electrospinning of collagen nanofibers. Biomacromolecules 2002; 3(2): 232–238, https://doi.org/10.1021/bm015533u.
110. Ohkawa K., Cha D., Kim H., Nishida A., Yamamoto H. Electrospinning of chitosan. Macromol Rapid Commun 2004; 25(18): 1600–1605, https://doi.org/10.1002/marc.200400253.
111. Ma Z., Kotaki M., Inai R., Ramakrishna S. Potential of nanofiber matrix as tissue-engineering scaffolds. Tissue Eng 2005; 11(1–2): 101–109, https://doi.org/10.1089/ten.2005.11.101.
112. Jakab K., Norotte C., Damon B., Marga F., Neagu A., Besch-Williford C.L., Kachurin A., Church K.H., Park H., Mironov V., Markwald R., Vunjak-Novakovic G., Forgacs G. Tissue engineering by self-assembly of cells printed into topologically defined structures. Tissue Eng Part A 2008; 14(3): 413–421, https://doi.org/10.1089/tea.2007.0173.
113. Norotte C., Marga F.S., Niklason L.E., Forgacs G. Scaffold-free vascular tissue engineering using bioprinting. Biomaterials 2009; 30(30): 5910–5917, https://doi.org/10.1016/j.biomaterials.2009.06.034.
114. Murphy S.V., Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol 2014; 32(8): 773–785, https://doi.org/10.1038/nbt.2958.
115. Wang Q., Xia Q., Wu Y., Zhang X., Wen F., Chen X., Zhang S., Heng B.C., He Y., Ouyang H.W. 3D-printed atsttrin-incorporated alginate/hydroxyapatite scaffold promotes bone defect regeneration with TNF/TNFR signaling involvement. Adv Healthc Mater 2015; 4(11): 1701–1708. https://doi.org/10.1002/adhm.201500211.
116. Agapov I.I., Moisenovich M.M., Vasilyeva T.V., Pustovalova O.L., Kon’kov A.S., Arkhipova A.Y., Sokolova O.S., Bogush V.G., Sevastianov V.I., Debabov V.G., Kirpichnikov M.P. Biodegradable matrices from regenerated silk of Bombix mori. Dokl Biochem Biophys 2010; 433: 201–204, https://doi.org/10.1134/s1607672910040149.
117. Agapov I.I., Pustovalova O.L., Moisenovich M.M., Bogush V.G., Sokolova O.S., Sevastyanov V.I., Debabov V.G., Kirpichnikov M.P. Three-dimensional scaffold made from recombinant spider silk protein for tissue engineering. Dokl Biochem Biophys 2009; 426(1): 127–130, https://doi.org/10.1134/s1607672909030016.
118. Varkey A., Venugopal E., Sugumaran P., Janarthanan G., Pillai M.M., Rajendran S., Bhattacharyya A. Impact of silk fibroin-based scaffold structures on human osteoblast MG63 cell attachment and proliferation. Int J Nanomedicine 2015; 10(Suppl 1): 43–51, https://doi.org/10.2147/ijn.s82209.
119. Sangkert S., Meesane J., Kamonmattayakul S., Chai W.L. Modified silk fibroin scaffolds with collagen/decellularized pulp for bone tissue engineering in cleft palate: morphological structures and biofunctionalities. Mater Sci Eng C Mater Biol Appl 2016; 58: 1138–1149, https://doi.org/10.1016/j.msec.2015.09.031.
120. Shao W., He J., Sang F., Ding B., Chen L., Cui S., Li K., Han Q., Tan W. Coaxial electrospun aligned tussah silk fibroin nanostructured fiber scaffolds embedded with hydroxyapatite-tussah silk fibroin nanoparticles for bone tissue engineering. Mater Sci Eng C Mater Biol Appl 2016; 58: 342–351, https://doi.org/10.1016/j.msec.2015.08.046.
121. Ding X., Zhu M., Xu B., Zhang J., Zhao Y., Ji S., Wang L., Wang L., Li X., Kong D., Ma X., Yang Q. Integrated trilayered silk fibroin scaffold for osteochondral differentiation of adipose-derived stem cells. ACS Appl Mater Interfaces 2014; 6(19): 16696–16705, https://doi.org/10.1021/am5036708.
122. Zeng S., Liu L., Shi Y., Qiu J., Fang W., Rong M., Guo Z., Gao W. Characterization of silk fibroin/chitosan 3D porous scaffold and in vitro cytology. PLoS One 2015; 10(6): e0128658, https://doi.org/10.1371/journal.pone.0128658.
123. Moisenovich M.M., Arkhipova A.Y., Orlova A.A., Drutskaya M.S., Volkova S.V., Zacharov S.E., Agapov I.I., Kirpichnikov M.P. Composite scaffolds containing silk fibroin, gelatin, and hydroxyapatite for bone tissue regeneration and 3D cell culturing. Acta Naturae 2014; 6(1): 96–101.
124. Tong S., Xu D.P., Liu Z.M., Du Y., Wang X.K. Synthesis of the new-type vascular endothelial growth factor-silk fibroin-chitosan three-dimensional scaffolds for bone tissue engineering and in vitro evaluation. J Craniofac Surg 2016; 27(2): 509–515, https://doi.org/10.1097/scs.0000000000002296.
125. Ming J., Jiang Z., Wang P., Bie S., Zuo B. Silk fibroin/sodium alginate fibrous hydrogels regulated hydroxyapatite crystal growth. Mater Sci Eng C Mater Biol Appl 2015; 51: 287–293, https://doi.org/10.1016/j.msec.2015.03.014.
126. Lyu X., Li Z., Wang H., Yang X. Bioactive glass 45S5-silk fibroin membrane supports proliferation and differentiation of human dental pulp stem cells. Zhonghua Kou Qiang Yi Xue Za Zhi 2015; 50(12): 725–730.
127. Wang X., Gu Z., Jiang B., Li L., Yu X. Surface modification of strontium-doped porous bioactive ceramic scaffolds via poly(DOPA) coating and immobilizing silk fibroin for excellent angiogenic and osteogenic properties. Biomater Sci 2016; 4(4): 678–688, https://doi.org/10.1039/c5bm00482a.
128. Zhang W., Zhu C., Ye D., et al. Porous silk scaffolds for delivery of growth factors and stem cells to enhance bone regeneration. PLoS One 2014; 9(7): e102371, https://doi.org/10.1371/journal.pone.0102371.
129. Gu Y., Chen L., Niu H.Y., Shen X.F., Yang H.L. Promoting spinal fusions by biomineralized silk fibroin films seeded with bone marrow stromal cells: an in vivo animal study. J Biomater Appl 2016; 30(8): 1251–1260, https://doi.org/10.1177/0885328215620067.
130. Luo Z., Jiang L., Xu Y., Li H., Xu W., Wu S., Wang Y., Tang Z., Lv Y., Yang L. Mechano growth factor (MGF) and transforming growth factor (TGF)-beta3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model. Biomaterials 2015; 52: 463–375, https://doi.org/10.1016/j.biomaterials.2015.01.001.
131. Vishwanath V., Pramanik K., Biswas A. Optimization and evaluation of silk fibroin-chitosan freeze dried porous scaffolds for cartilage tissue engineering application. J Biomater Sci Polym Ed 2016; 27(7): 657–674, https://doi.org/10.1080/09205063.2016.1148303.
132. Wang J., Yang Q., Cheng N., Tao X., Zhang Z., Sun X., Zhang Q. Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair. Mater Sci Eng C Mater Biol Appl 2016; 61: 705–511, https://doi.org/10.1016/j.msec.2015.12.097.
133. Lan Y., Li W., Jiao Y., Guo R., Zhang Y., Xue W., Zhang Y. Therapeutic efficacy of antibiotic-loaded gelatin microsphere/silk fibroin scaffolds in infected full-thickness burns. Acta Biomater 2014; 10(7): 3167–3176, https://doi.org/10.1016/j.actbio.2014.03.029.
134. Ju H.W., Lee O.J., Lee J.M., Moon B.M., Park H.J., Park Y.R., Lee M.C., Kim S.H., Chao J.R., Ki C.S., Park C.H. Wound healing effect of electrospun silk fibroin nanomatrix in burn-model. Int J Biol Macromol 2016; 85: 29–39, https://doi.org/10.1016/j.ijbiomac.2015.12.055.
135. Navone S.E., Pascucci L., Dossena M., Ferri A., Invernici G., Acerbi F., Cristini S., Bedini G., Tosetti V., Ceserani V., Bonomi A., Pessina A., Freddi G., Alessandrino A., Ceccarelli P., Campanella R., Marfia G., Alessandri G., Parati E.A. Decellularized silk fibroin scaffold primed with adipose mesenchymal stromal cells improves wound healing in diabetic mice. Stem Cell Res Ther 2014; 5(1): 7, https://doi.org/10.1186/scrt396.
136. Floren M., Bonani W., Dharmarajan A., Motta A., Migliaresi C., Tan W. Human mesenchymal stem cells cultured on silk hydrogels with variable stiffness and growth factor differentiate into mature smooth muscle cell phenotype. Acta Biomater 2016; 31: 156–166, https://doi.org/10.1016/j.actbio.2015.11.051.
137. Chomachayi M.D., Solouk A., Mirzadeh H. Electrospun silk-based nanofibrous scaffolds: fiber diameter and oxygen transfer. Prog Biomater 2016; 5: 71–80, https://doi.org/10.1007/s40204-016-0046-6.
138. Wu H.Y., Zhang F., Yue X.X., Ming J.F., Zuo B.Q. Wet-spun silk fibroin scaffold with hierarchical structure for ligament tissue engineering. Materials Letters 2014; 135: 63–66, https://doi.org/10.1016/j.matlet.2014.07.115.
139. Jiang J., Ai C., Zhan Z., Zhang P., Wan F., Chen J., Hao W., Wang Y., Yao J., Shao Z., Chen T., Zhou L., Chen S. Enhanced fibroblast cellular ligamentization process to polyethylene terepthalate artificial ligament by silk fibroin coating. Artif Organs 2016; 40(4): 385–393, https://doi.org/10.1111/aor.12571.
140. Bi F., Shi Z., Liu A., Guo P., Yan S. Anterior cruciate ligament reconstruction in a rabbit model using silk-collagen scaffold and comparison with autograft. PLoS One 2015; 10(5): e0125900, https://doi.org/10.1371/journal.pone.0125900.
141. Naghashzargar E., Farè S., Catto V., Bertoldi S., Semnani D., Karbasi S., Tanzi M.C. Nano/micro hybrid scaffold of PCL or P3HB nanofibers combined with silk fibroin for tendon and ligament tissue engineering. J Appl Biomater Funct Mater 2015; 13(2): e156–e168, https://doi.org/10.5301/jabfm.5000216.
142. Zhu M., Wang K., Mei J., Li C., Zhang J., Zheng W., An D., Xiao N., Zhao Q., Kong D., Wang L. Fabrication of highly interconnected porous silk fibroin scaffolds for potential use as vascular grafts. Acta Biomater 2014; 10(5): 2014–2023, https://doi.org/10.1016/j.actbio.2014.01.022.
143. Catto V., Farè S., Cattaneo I., Figliuzzi M., Alessandrino A., Freddi G., Remuzzi A., Tanzi M.C. Small diameter electrospun silk fibroin vascular grafts: Mechanical properties, in vitro biodegradability, and in vivo biocompatibility. Mater Sci Eng C Mater Biol Appl 2015; 54: 101–111, https://doi.org/10.1016/j.msec.2015.05.003.
144. Zhang W., Wray L.S., Rnjak-Kovacina J., Xu L., Zou D., Wang S., Zhang M., Dong J., Li G., Kaplan D.L., Jiang X. Vascularization of hollow channel-modified porous silk scaffolds with endothelial cells for tissue regeneration. Biomaterials 2015; 56: 68–77, https://doi.org/10.1016/j.biomaterials.2015.03.053.
145. Seib F.P., Herklotz M., Burke K.A., Maitz M.F., Werner C., Kaplan D.L. Multifunctional silk-heparin biomaterials for vascular tissue engineering applications. Biomaterials 2014; 35(1): 83–91, https://doi.org/10.1016/j.biomaterials.2013.09.053.
146. Zhao L., Xu Y., He M., Zhang W., Li M. Preparation of spider silk protein bilayer small-diameter vascular scaffold and its biocompatibility and mechanism research. Composite Interfaces 2014; 21(9): 869–884, https://doi.org/10.1080/15685543.2014.970416.
147. Aytemiz D., Suzuki Y., Shindo T., Saotome T., Tanaka R., Asakura T. In vitro and in vivo evaluation of hemocompatibility of silk fibroin based artificial vascular grafts. Int J Chem 2014; 6(2), https://doi.org/10.5539/ijc.v6n2p1.
148. Adali T., Uncu M. Silk fibroin as a non-thrombogenic biomaterial. Int J Biol Macromol 2016; 90: 11–19, https://doi.org/10.1016/j.ijbiomac.2016.01.088.
149. Franck D., Chung Y.G., Coburn J., Kaplan D.L., Estrada C.R. Jr., Mauney J.R. In vitro evaluation of bi-layer silk fibroin scaffolds for gastrointestinal tissue engineering. J Tissue Eng 2014; 5: 2041731414556849, https://doi.org/10.1177/2041731414556849.
150. Hou L., Gong C., Zhu Y. In vitro construction and in vivo regeneration of esophageal bilamellar muscle tissue. J Biomater Appl 2016; 30(9): 1373–1384, https://doi.org/10.1177/0885328215627585.
151. Sack B.S., Mauney J.R., Estrada C.R. Jr. Silk fibroin scaffolds for urologic tissue engineering. Curr Urol Rep 2016; 17(2): 16, https://doi.org/10.1007/s11934-015-0567-x.
152. Steins A., Dik P., Müller W.H., Vervoort S.J., Reimers K., Kuhbier J.W., Vogt P.M., van Apeldoorn A.A., Coffer P.J., Schepers K. In vitro evaluation of spider silk meshes as a potential biomaterial for bladder reconstruction. PLoS One 2015; 10(12): e0145240, https://doi.org/10.1371/journal.pone.0145240.
153. Lv X., Li Z., Chen S., Xie M., Huang J., Peng X., Yang R., Wang H., Xu Y., Feng C. Structural and functional evaluation of oxygenating keratin/silk fibroin scaffold and initial assessment of their potential for urethral tissue engineering. Biomaterials 2016; 84: 99–110, https://doi.org/10.1016/j.biomaterials.2016.01.032.
154. Zhang C., Zhang Y., Shao H., Hu X. Hybrid silk fibers dry-spun from regenerated silk fibroin/graphene oxide aqueous solutions. ACS Appl Mater Interfaces 2016; 8(5): 3349–3358, https://doi.org/10.1021/acsami.5b11245.
155. Xu Y., Zhang Z., Chen X., Li R., Li D., Feng S. A silk fibroin/collagen nerve scaffold seeded with a co-culture of schwann cells and adipose-derived stem cells for sciatic nerve regeneration. PLoS One 2016; 11(1): e0147184, https://doi.org/10.1371/journal.pone.0147184.
156. Chwalek K., Sood D., Cantley W.L., White J.D., Tang-Schomer M., Kaplan D.L. Engineered 3D silk-collagen-based model of polarized neural tissue. J Vis Exp 2015; 105: e52970, https://doi.org/10.3791/52970.
157. Wang Y.L., Gu X.M., Kong Y., Feng Q.L., Yang Y.M. Electrospun and woven silk fibroin/poly(lactic-co-glycolic acid) nerve guidance conduits for repairing peripheral nerve injury. Neural Regen Res 2015; 10(10): 1635–1642, https://doi.org/10.4103/1673-5374.167763.
158. Moisenovich M.M., Malyuchenko N.V., Arkhipova A.Y., Kotlyarova M.S., Davydova L.I., Goncharenko A.V., Agapova O.I., Drutskaya M.S., Bogush V.G., Agapov I.I., Debabov V.G., Kirpichnikov M.P. Novel 3D-microcarriers from recombinant spidroin for regenerative medicine. Dokl Biochem Biophys 2015; 463: 232–235, https://doi.org/10.1134/s1607672915040109.
159. Arkhipova A.Y., Kotlyarova M.C., Novichkova S.G., Agapova O.I., Kulikov D.A., Kulikov A.V., Drutskaya M.S., Agapov I.I., Moisenovich M.M. New silk fibroin-based bioresorbable microcarriers. Bull Exp Biol Med 2016; 160(4): 491–494, https://doi.org/10.1007/s10517-016-3204-x.
160. Zhang S.S., Li J.J., Zhang X.F., Lu S.Z. Corneal matrix repair carrier with composite silk protein membrane. Materials Science Forum 2015; 815: 424–428, https://doi.org/10.4028/www.scientific.net/msf.815.424.
161. Teplenin A., Krasheninnikova A., Agladze N., Sidoruk K., Agapova O., Agapov I., Bogush V., Agladze K. Functional analysis of the engineered cardiac tissue grown on recombinant spidroin fiber meshes. PLoS One 2015; 10(3): e0121155, https://doi.org/10.1371/journal.pone.0121155.
162. Lerdchai K., Kitsongsermthon J., Ratanavaraporn J., Kanokpanont S., Damrongsakkul S. Thai silk fibroin/gelatin sponges for the dual controlled release of curcumin and docosahexaenoic acid for anticancer treatment. J Pharm Sci 2016; 105(1): 221–230, https://doi.org/10.1002/jps.24701.
163. Cheng C., Teasdale I., Brüggemann O. Stimuli-responsive capsules prepared from regenerated silk fibroin microspheres. Macromol Biosci 2014; 14(6): 807–816, https://doi.org/10.1002/mabi.201300497.
164. Zeng D.M., Pan J.J., Wang Q., Liu X.F., Wang H., Zhang K.Q. Controlling silk fibroin microspheres via molecular weight distribution. Mater Sci Eng C Mater Biol Appl 2015; 50: 226–233, https://doi.org/10.1016/j.msec.2015.02.005.
165. Zhang H., Ma X., Cao C., Wang M., Zhu Y. Multifunctional iron oxide/silk-fibroin (Fe3O4–SF) composite microspheres for the delivery of cancer therapeutics. RSC Adv 2014; 4(78): 41572–41577, https://doi.org/10.1039/c4ra05919k.
166. Agostini E., Winter G., Engert J. Water-based preparation of spider silk films as drug delivery matrices. J Control Release 2015; 213: 134–141, https://doi.org/10.1016/j.jconrel.2015.06.025.
167. Yucel T., Lovett M.L., Giangregorio R., Coonahan E., Kaplan D.L. Silk fibroin rods for sustained delivery of breast cancer therapeutics. Biomaterials 2014; 35(30): 8613–8620, https://doi.org/10.1016/j.biomaterials.2014.06.030.
168. Sharma S., Bano S., Ghosh A.S., Mandal M., Kim H.W., Dey T., Kundu S.C. Silk fibroin nanoparticles support in vitro sustained antibiotic release and osteogenesis on titanium surface. Nanomedicine 2016; 12(5): 1193–1204, https://doi.org/10.1016/j.nano.2015.12.385.
169. Li X., Qin J., Ma J. Silk fibroin/poly (vinyl alcohol) blend scaffolds for controlled delivery of curcumin. Regen Biomater 2015; 2(2): 97–105, https://doi.org/10.1093/rb/rbv008.
170. Kim S.Y., Naskar D., Kundu S.C., Bishop D.P., Doble P.A., Boddy A.V., Chan H.K., Wall I.B., Chrzanowski W. Formulation of biologically-inspired silk-based drug carriers for pulmonary delivery targeted for lung cancer. Sci Rep 2015; 5: 11878, https://doi.org/10.1038/srep11878.
171. Florczak A., Mackiewicz A., Dams-Kozlowska H. Functionalized spider silk spheres as drug carriers for targeted cancer therapy. Biomacromolecules 2014; 15(8): 2971–2981, https://doi.org/10.1021/bm500591p.
172. Yu D., Sun C., Zheng Z., Wang X., Chen D., Wu H., Wang X., Shi F. Inner ear delivery of dexamethasone using injectable silk-polyethylene glycol (PEG) hydrogel. Int J Pharm 2016; 503(1–2): 229–237, https://doi.org/10.1016/j.ijpharm.2016.02.048.
173. Applegate M.B., Partlow B.P., Coburn J., Marelli B., Pirie C., Pineda R., Kaplan D.L., Omenetto F.G. Photocrosslinking of silk fibroin using riboflavin for ocular prostheses. Adv Mater 2016; 28(12): 2417–2420, https://doi.org/10.1002/adma.201504527.
174. Khalid A., Mitropoulos A.N., Marelli B., Tomljenovic-Hanic S., Omenetto F.G. Doxorubicin loaded nanodiamond-silk spheres for fluorescence tracking and controlled drug release. Biomed Opt Express 2016; 7(1): 132–147, https://doi.org/10.1364/boe.7.000132.

Agapova O.I. Silk Fibroin and Spidroin Bioengineering Constructions for Regenerative Medicine and Tissue Engineering (Review). Sovremennye tehnologii v medicine 2017; 9(2): 190, https://doi.org/10.17691/stm2017.9.2.24