Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Thermoplastic moulding of regenerated silk


Early insights into the unique structure and properties of native silk suggested that β-sheet nanocrystallites in silk would degrade prior to melting when subjected to thermal processing. Since then, canonical approaches for fabricating silk-based materials typically involve solution-derived processing methods, which have inherent limitations with respect to silk protein solubility and stability in solution, and time and cost efficiency. Here we report a thermal processing method for the direct solid-state moulding of regenerated silk into bulk ‘parts’ or devices with tunable mechanical properties. At elevated temperature and pressure, regenerated amorphous silk nanomaterials with ultralow β-sheet content undergo thermal fusion via molecular rearrangement and self-assembly assisted by bound water to form a robust bulk material that retains biocompatibility, degradability and machinability. This technique reverses presumptions about the limitations of direct thermal processing of silk into a wide range of new material formats and composite materials with tailored properties and functionalities.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Process to generate silk-based bulk materials from native silk.
Fig. 2: Comparison of degummed natural silk fibre and ASN.
Fig. 3: Thermal processing of ASN.
Fig. 4: Physical properties of fabricated silk-based bulk materials.
Fig. 5: In vitro and in vivo testing of functional silk-based medical devices.

Data availability

The authors declare that all data supporting the findings of this study are available within the paper and its Supplementary Information files and from the corresponding author upon reasonable request.


  1. 1.

    Vepari, C. & Kaplan, D. L. Silk as a biomaterial. Prog. Polym. Sci. 32, 991–1007 (2007).

    CAS  Google Scholar 

  2. 2.

    Vollrath, F. & Porter, D. Spider silk as archetypal protein elastomer. Soft Matter 2, 377–385 (2006).

    CAS  Google Scholar 

  3. 3.

    Vollrath, F. & Knight, D. P. Liquid crystalline spinning of spider silk. Nature 410, 541–548 (2001).

    CAS  Google Scholar 

  4. 4.

    Shao, Z. Z. & Vollrath, F. Materials: surprising strength of silkworm silk. Nature 418, 741 (2002).

    CAS  Google Scholar 

  5. 5.

    Jin, H. J. & Kaplan, D. L. Mechanism of silk processing in insects and spiders. Nature 424, 1057–1061 (2003).

    CAS  Google Scholar 

  6. 6.

    Askarieh, G. et al. Self-assembly of spider silk proteins is controlled by a pH-sensitive relay. Nature 465, 236–238 (2010).

    CAS  Google Scholar 

  7. 7.

    Hagn, F. et al. A conserved spider silk domain acts as a molecular switch that controls fibre assembly. Nature 465, 239–242 (2010).

    CAS  Google Scholar 

  8. 8.

    Andersson, M., Johansson, J. & Rising, A. Silk spinning in silkworms and spiders. Int. J. Mol. Sci. 17, 1290–1303 (2016).

    Google Scholar 

  9. 9.

    Yarger, J. L., Cherry, B. R. & van der Vaart, A. Uncovering the structure-function relationship in spider silk. Nat. Rev. Mater. 3, 18008–18018 (2018).

    CAS  Google Scholar 

  10. 10.

    Guo, C. et al. Structural comparison of various silkworm silks: an insight into the structure-property relationship. Biomacromolecules 19, 906–917 (2018).

    CAS  Google Scholar 

  11. 11.

    Rockwood, D. N. et al. Materials fabrication from Bombyx mori silk fibroin. Nat. Protoc. 6, 1612–1631 (2011).

    CAS  Google Scholar 

  12. 12.

    Teule, F. et al. A protocol for the production of recombinant spider silk-like proteins for artificial fiber spinning. Nat. Protoc. 4, 341–355 (2009).

    CAS  Google Scholar 

  13. 13.

    Heim, M., Keerl, D. & Scheibel, T. Spider silk: from soluble protein to extraordinary fiber. Angew. Chem. Int. Edit. 48, 3584–3596 (2009).

    CAS  Google Scholar 

  14. 14.

    Andersson, M. et al. Biomimetic spinning of artificial spider silk from a chimeric minispidroin. Nat. Chem. Biol. 13, 262–264 (2017).

    CAS  Google Scholar 

  15. 15.

    Zhou, Z. et al. Engineering the future of silk materials through advanced manufacturing. Adv. Mater. 30, 1706983–1707008 (2018).

    Google Scholar 

  16. 16.

    Kundu, B., Rajkhowa, R., Kundu, S. C. & Wang, X. Silk fibroin biomaterials for tissue regenerations. Adv. Drug Deliv. Rev. 65, 457–470 (2013).

    CAS  Google Scholar 

  17. 17.

    Abbott, R. D., Kimmerling, E. P., Cairns, D. M. & Kaplan, D. L. Silk as a biomaterial to support long-term three-dimensional tissue cultures. ACS Appl. Mater. Interfaces 8, 21861–21868 (2016).

    CAS  Google Scholar 

  18. 18.

    Bhattacharjee, P. et al. Silk scaffolds in bone tissue engineering: an overview. Acta Biomater. 63, 1–17 (2017).

    CAS  Google Scholar 

  19. 19.

    Crivelli, B. et al. Silk nanoparticles: from inert supports to bioactive natural carriers for drug delivery. Soft Matter 14, 546–557 (2018).

    CAS  Google Scholar 

  20. 20.

    Holland, C., Numata, K., Rnjak-Kovacina, J. & Seib, F. P. The biomedical use of silk: past, present, future. Adv. Healthc. Mater. 8, 1800465–1800490 (2019).

    Google Scholar 

  21. 21.

    Koh, L.-D. et al. Structures, mechanical properties and applications of silk fibroin materials. Prog. Polym. Sci. 46, 86–110 (2015).

    CAS  Google Scholar 

  22. 22.

    Pauling, L. & Corey, R. B. The pleated sheet, a new layer configuration of polypeptide chains. Proc. Natl Acad. Sci. USA 37, 251–256 (1951).

    CAS  Google Scholar 

  23. 23.

    Marsh, R. E., Corey, R. B. & Pauling, L. An investigation of the structure of silk fibroin. Biochim. Biophys. Acta 16, 1–34 (1955).

    CAS  Google Scholar 

  24. 24.

    Keten, S., Xu, Z., Ihle, B. & Buehler, M. J. Nanoconfinement controls stiffness, strength and mechanical toughness of beta-sheet crystals in silk. Nat. Mater. 9, 359–367 (2010).

    CAS  Google Scholar 

  25. 25.

    Liang, C. X. & Hirabayashi, K. Influence of solvation temperature on the molecular-features and physical-properties of fibroin membrane. Polymer 33, 4388–4393 (1992).

    CAS  Google Scholar 

  26. 26.

    Trabbic, K. A. & Yager, P. Comparative structural characterization of naturally- and synthetically-spun fibers of Bombyx mori fibroin. Macromolecules 31, 462–471 (1998).

    CAS  Google Scholar 

  27. 27.

    Ha, S. W., Tonelli, A. E. & Hudson, S. M. Structural studies of Bombyx mori silk fibroin during regeneration from solutions and wet fiber spinning. Biomacromolecules 6, 1722–1731 (2005).

    CAS  Google Scholar 

  28. 28.

    Cheng, G., Wang, X., Tao, S., Xia, J. & Xu, S. Differences in regenerated silk fibroin prepared with different solvent systems: from structures to conformational changes. J. Appl. Polym. Sci. 132, 41959–41966 (2015).

    Google Scholar 

  29. 29.

    Marelli, B. et al. Programming function into mechanical forms by directed assembly of silk bulk materials. Proc. Natl Acad. Sci. USA 114, 451–456 (2017).

    CAS  Google Scholar 

  30. 30.

    Yamaguchi, K. et al. Primary structure of the silk fibroin light chain determined by cDNA sequencing and peptide analysis. J. Mol. Biol. 210, 127–139 (1989).

    CAS  Google Scholar 

  31. 31.

    Zhou, C. Z. et al. Silk fibroin: structural implications of a remarkable amino acid sequence. Proteins 44, 119–122 (2001).

    CAS  Google Scholar 

  32. 32.

    Suzuki, Y., Yamazaki, T., Aoki, A., Shindo, H. & Asakura, T. NMR study of the structures of repeated sequences, GAGXGA (X = S, Y, V), in Bombyx mori liquid silk. Biomacromolecules 15, 104–112 (2014).

    CAS  Google Scholar 

  33. 33.

    Hu, X., Kaplan, D. & Cebe, P. Effect of water on the thermal properties of silk fibroin. Thermochim. Acta 461, 137–144 (2007).

    CAS  Google Scholar 

  34. 34.

    Agarwal, N., Hoagland, D. A. & Farris, R. J. Effect of moisture absorption on the thermal properties of Bombyx mori silk fibroin films. J. Appl. Polym. Sci. 63, 401–410 (1997).

    CAS  Google Scholar 

  35. 35.

    Yazawa, K., Ishida, K., Masunaga, H., Hikima, T. & Numata, K. Influence of water content on the beta-sheet formation, thermal stability, water removal, and mechanical properties of silk materials. Biomacromolecules 17, 1057–1066 (2016).

    CAS  Google Scholar 

  36. 36.

    Brenckle, M. A. et al. Protein-protein nanoimprinting of silk fibroin films. Adv. Mater. 25, 2409–2414 (2013).

    CAS  Google Scholar 

  37. 37.

    Brenckle, M. A. et al. Methods and applications of multilayer silk fibroin laminates based on spatially controlled welding in protein films. Adv. Funct. Mater. 26, 44–50 (2016).

    CAS  Google Scholar 

  38. 38.

    Cebe, P. et al. Beating the heat—fast scanning melts silk beta sheet crystals. Sci. Rep. 3, 1130–1136 (2013).

    Google Scholar 

  39. 39.

    Lu, Q. et al. Silk self-assembly mechanisms and control from thermodynamics to kinetics. Biomacromolecules 13, 826–832 (2012).

    CAS  Google Scholar 

  40. 40.

    Koebley, S. R. et al. Silk reconstitution disrupts fibroin self-assembly. Biomacromolecules 16, 2796–2804 (2015).

    CAS  Google Scholar 

  41. 41.

    Perrone, G. S. et al. The use of silk-based devices for fracture fixation. Nat. Commun. 5, 3385–3393 (2014).

    Google Scholar 

  42. 42.

    Li, C. et al. Regenerated silk materials for functionalized silk orthopedic devices by mimicking natural processing. Biomaterials 110, 24–33 (2016).

    CAS  Google Scholar 

  43. 43.

    Liu, K. et al. A silk cranial fixation system for neurosurgery. Adv. Healthc. Mater. 7, 1701359–1701371 (2018).

    Google Scholar 

  44. 44.

    Guziewicz, N. A., Massetti, A. J., Perez-Ramirez, B. J. & Kaplan, D. L. Mechanisms of monoclonal antibody stabilization and release from silk biomaterials. Biomaterials 34, 7766–7775 (2013).

    CAS  Google Scholar 

  45. 45.

    Li, A. B., Kluge, J. A., Guziewicz, N. A., Omenetto, F. G. & Kaplan, D. L. Silk-based stabilization of biomacromolecules. J. Control. Release 219, 416–430 (2015).

    CAS  Google Scholar 

  46. 46.

    Lee, J. H. et al. Preparation of new natural silk non-woven fabrics by using adhesion characteristics of sericin and their characterization. Int. J. Biol. Macromol. 106, 39–47 (2018).

    CAS  Google Scholar 

  47. 47.

    Kluge, J. A., Kahn, B. T., Brown, J. E., Omenetto, F. G. & Kaplan, D. L. Optimizing molecular weight of lyophilized silk as a shelf-stable source material. ACS Biomater. Sci. Eng. 2, 595–605 (2016).

    CAS  Google Scholar 

  48. 48.

    Wegst, U. G., Bai, H., Saiz, E., Tomsia, A. P. & Ritchie, R. O. Bioinspired structural materials. Nat. Mater. 14, 23–36 (2015).

    CAS  Google Scholar 

  49. 49.

    Mao, L. B. et al. Synthetic nacre by predesigned matrix-directed mineralization. Science 354, 107–110 (2016).

    CAS  Google Scholar 

Download references


This work was supported by grants from the National Institutes of Health (R01AR068048, R01DE016525), the Air Force Office of Scientific Research (FA9550-17-1-0333) and the Stepping Strong Foundation, Brigham and Women’s Hospital (A. Nazarian and G. Dyer). We thank J. Yarger, B. Cherry and N. Sisco at Arizona State University for help with NMR instrumentation and data collection. We thank G. Dyer for clinical relevance discussions. We also thank S. Maccorkle and D. Dupuis at the Tufts University Machine Shop for materials machining.

Author information




C.G., C.L and D.L.K. conceived and designed the project and experiments; C.G., C.L., H.V.V. and Y.Q. performed the materials fabrication and characterizations; P.H., A.L. and A.N. performed animal studies; C.G., C.L., X.M., S.L. and S.J.L. performed the data analysis and results discussion; D.L.K. supervised the entire project; and C.G. and C.L. wrote the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Chunmei Li or David L. Kaplan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary information

Supplementary Figures 1–27, Tables 1–8, a note and refs. 1–7.

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Guo, C., Li, C., Vu, H.V. et al. Thermoplastic moulding of regenerated silk. Nat. Mater. 19, 102–108 (2020).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing