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Functionalization of silk fibroin-based biomaterials for tissue engineering

Polymer Journal volume 53, pages 1345–1351 (2021)Cite this article

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Abstract

Silk fibroin (SF) is a natural protein polymer material approved by the US Food and Drug Administration for clinical use, such as for surgical sutures. In addition, SF has been fabricated and studied as a scaffold for tissue engineering and regenerative medicine. To append new functions to SF scaffolds and understand their in vivo behaviors, researchers have addressed modifications of SF scaffolds by using transgenic silkworm and peptide modification technologies. These modified SF scaffolds had on-target functions and showed their potential as a material for tissue engineering applications. This review summarizes the methodologies and characteristics of functionalized SF scaffolds.

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References

  1. Jewell M, Daunch W, Bengtson B, Mortarino E. The development of SERI® Surgical Scaffold, an engineered biological scaffold. Ann N Y Acad Sci. 2015;1358:44–55.

    Article  CAS  Google Scholar 

  2. Rockwood DN, Preda RC, Yücel T, Wang X, Lovett ML, Kaplan DL. Materials fabrication from Bombyx mori silk fibroin. Nat Protoc. 2011;6:1612–31.

    Article  CAS  Google Scholar 

  3. Holland C, Numata K, Rnjak-Kovacina J, Seib FP. The biomedical use of silk: past, present, future. Adv Healthc Mater. 2019;8:1800465.

    Article  Google Scholar 

  4. Leal-Egaña A, Scheibel T. Interactions of cells with silk surfaces. J Mater Chem. 2012;22:14330–6.

    Article  Google Scholar 

  5. Kambe Y, Mizoguchi Y, Kuwahara K, Nakaoki T, Hirano Y, Yamaoka T. Beta-sheet content significantly correlates with the biodegradation time of silk fibroin hydrogels showing a wide range of compressive modulus. Polym Degrad Stab. 2020;179:109240.

    Article  CAS  Google Scholar 

  6. Tamura T, Thibert C, Royer C, Kanda T, Eappen A, Kamba M, et al. Germline transformation of the silkworm Bombyx mori L. using a piggyBac transposon-derived vector. Nat Biotechnol. 2000;18:81–84.

    Article  CAS  Google Scholar 

  7. Sasaki T, Noda H. Studies on silk fibroin of Bombyx mori directly extracted from the silk gland: I. Molecular weight determination in guanidine hydrochloride or urea solutions. Biochim Biophys Acta. 1973;310:76–90.

    Article  CAS  Google Scholar 

  8. Yamaguchi K, Kikuchi Y, Takagi T, Kikuchi A, Oyama F, Shimura K, et al. Primary structure of the silk fibroin light chain determined by cDNA sequencing and peptide analysis. J Mol Biol. 1989;210:127–39.

    Article  CAS  Google Scholar 

  9. 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;29:269–76.

    Article  CAS  Google Scholar 

  10. 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;275:40517–28.

    Article  CAS  Google Scholar 

  11. Kambe Y, Yamamoto K, Katsura K, Tamada Y, Tomita N. Effects of RGDS sequence genetically interfused in the silk fibroin light chain protein on chondrocyte adhesion and cartilage synthesis. Biomaterials. 2010;31:7503–11.

    Article  CAS  Google Scholar 

  12. Rouslahti E, Pierschbacher MD. Arg-Gly-Asp: a versatile cell recognition signal. Cell. 1986;44:517–8.

    Article  Google Scholar 

  13. Kambe Y, Takeda Y, Yamamoto K, Katsura K, Tamada Y, Tomita N. Effect of RGDS-expressing fibroin dose on initial adhesive force of a single chondrocyte. Biomed Mater Eng. 2010;20:309–16.

    CAS  PubMed  Google Scholar 

  14. Tamada Y. New process to form a silk fibroin porous 3-D structure. Biomacromolecules. 2005;6:3100–6.

    Article  CAS  Google Scholar 

  15. Westall FC, Rubin R, Gospodarowicz D. Brain-derived fibroblast growth factor: a study of its inactivation. Life Sci. 1983;33:2425–9.

    Article  CAS  Google Scholar 

  16. Caccia P, Nitti G, Cletini O, Pucci P, Ruoppolo M, Bertolero F, et al. Stabilization of recombinant human basic fibroblast growth factor by chemical modification of cysteine residues. Eur J Biochem. 1992;204:649–55.

    Article  CAS  Google Scholar 

  17. Estapé D, van den Heuvel J, Rinas U. Susceptibility toward intramolecular disulfide-bond formation affects conformational stability and folding of human basic fibroblast growth factor. Biochem J. 1998;335:343–9.

    Article  Google Scholar 

  18. Cuevasa P, Burgosa J, Baird A. Basic fibroblast growth factor (FGF) promotes cartilage repair in vivo. Biochem Biophys Res Commun. 1988;156:611–8.

    Article  Google Scholar 

  19. Kambe Y, Kojima K, Tamada Y, Tomita N, Kameda T. Silk fibroin sponges with cell growth-promoting activity induced by genetically fused basic fibroblast growth factor. J Biomed Mater Res Part A. 2016;104:82–93.

    Article  Google Scholar 

  20. Kambe Y, Tamada Y, Kameda T. Effects of phosphate, tris, HEPES, or MOPS buffers on the formation of silk fibroin sponges. J Silk Sci Technol Jpn. 2018;26:21–30.

    Google Scholar 

  21. Tomita M. Transgenic silkworms that weave recombinant proteins into silk cocoons. Biotechnol Lett. 2011;33:645–54.

    Article  CAS  Google Scholar 

  22. Kambe Y, Murakoshi A, Urakawa H, Kimura Y, Yamaoka T. Vascular induction and cell infiltration into peptide-modified bioactive silk fibroin hydrogels. J Mater Chem B. 2017;5:7557–71.

    Article  CAS  Google Scholar 

  23. Wang X, Kluge JA, Leisk GG, Kaplan DL. Sonication-induced gelation of silk fibroin for cell encapsulation. Biomaterials. 2008;29:1054–64.

    Article  CAS  Google Scholar 

  24. Yucel T, Cebe P, Kaplan DL. Vortex-induced injectable silk fibroin hydrogels. Biophys J. 2009;97:2044–50.

    Article  CAS  Google Scholar 

  25. Matsumoto A, Chen J, Collette AL, Kim UJ, Altman GH, Cebe P, et al. Mechanisms of silk fibroin sol-gel transitions. J Phys Chem B. 2006;110:21630–8.

    Article  CAS  Google Scholar 

  26. Zhang W, Wang X, Wang S, Zhao J, Xu L, Zhu C, et al. The use of injectable sonication-induced silk hydrogel for VEGF165 and BMP-2 delivery for elevation o the maxillary sinus floor. Biomaterials. 2011;32:9415–24.

    Article  CAS  Google Scholar 

  27. Kambe Y, Yamaoka T. Biodegradation of injectable silk fibroin hydrogel prevents negative left ventricular remodeling after myocardial infarction. Biomater Sci. 2019;7:4153–65.

    Article  CAS  Google Scholar 

  28. Rane AA, Christman KL. Biomaterials for the treatment of myocardial infarction. A 5-year update. J Am Coll Cardiol 2011;58:2615–29.

    Article  CAS  Google Scholar 

  29. Zhu Y, Matsumura Y, Wagner WR. Ventricular wall biomaterial injection therapy after myocardial infarction: advances in material design, mechanistic insight and early clinical experiences. Biomaterials. 2017;129:37–53.

    Article  CAS  Google Scholar 

  30. Tous E, Ifkovitz JI, Koomalsingh KJ, Shuto T, Soeda T, Kondo N, et al. Influence of injectable hyaluronic acid hydrogel degradation behavior on infarction-induced ventricular remodeling. Biomacromolecules. 2011;12:4127–35.

    Article  CAS  Google Scholar 

  31. Wang Y, Rudym DD, Walsh A, Abrahamsen L, Kim HJ, Kim HS, et al. In vivo degradation of three-dimensional silk fibroin scaffolds. Biomaterials. 2008;29:3415–28.

    Article  CAS  Google Scholar 

  32. Kambe Y, Yamaoka T. Initial immune response to a FRET-based MMP sensor-immobilized silk fibroin hydrogel in vivo. Acta Biomater. 2021;130:199–210.

  33. Power G, Moore Z, O′Connor T. Measurement of pH, exudate composition and temperature in wound healing: a systematic review. J Wound Care. 2017;26:381–97.

    Article  CAS  Google Scholar 

  34. Brown J, Lu CL, Coburn J, Kaplan DL. Impact of silk biomaterial structure on proteolysis. Acta Biomater. 2015;11:212–21.

    Article  CAS  Google Scholar 

  35. Teramoto H, Kojima K. Production of Bombyx mori silk fibroin incorporated with unnatural amino acids. Biomacromolecules. 2014;15:2682–90.

    Article  CAS  Google Scholar 

  36. Chantawong P, Tanaka T, Uemura A, Shimada K, Higuchi A, Tajiri H, et al. Silk fibroin-Pellethane® cardiovascular patches: effect of silk fibroin concentration on vascular remodeling in rat model. J Mater Sci: Mater Med. 2017;28:191.

    Google Scholar 

  37. Hong H, Seo YB, Kim DY, Lee JS, Lee YJ, Lee H, et al. Digital light processing 3D printed silk fibroin hydrogel for cartilage tissue engineering. Biomaterials. 2020;232:119679.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was financially supported by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (B) (grant no. 20H04509).

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Authors and Affiliations

  1. Silk Materials Research Group, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO), Tsukuba, Ibaraki, Japan

    Yusuke Kambe

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  1. Yusuke Kambe
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Yusuke Kambe: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Writing-original draft, Writing-review & editing.

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Correspondence to Yusuke Kambe.

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Kambe, Y. Functionalization of silk fibroin-based biomaterials for tissue engineering. Polym J 53, 1345–1351 (2021). https://doi.org/10.1038/s41428-021-00536-5

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