Skip to main content
Log in

Injectable silk fibroin/polyurethane composite hydrogel for nucleus pulposus replacement

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

In degenerative disc disease, an injectable hydrogel can fill a degenerate area completely, reduce the risk of implant migration and subsequent loss of height of the intervertebral disc, and minimise surgical defects. Here, we propose a method of preparing an injectable silk fibroin/polyurethane (SF/PU) composite hydrogel by chemical cross-linking under physiological conditions. Mechanical testing was used to determine the mechanical strength of the hydrogel. The impact of hydrogel height on the biomechanical properties was discussed to estimate the working capacity of the hydrogel for further clinical application. Rheological properties were also examined to assess the practical ability of the hydrogel for clinical application. Hydrogel injection and cell assessment is also of interest for clinical application. An SF/PU composite hydrogel can be injected through a small incision. A cell proliferation assay using bone marrow stromal cells showed positive cell viability and increased proliferation over a seven-day period in culture. Importantly, the hydrogel can be monitored in real-time using X-ray fluoroscopy during and after surgery according to the results of X-ray fluoroscopy examination, and shows good visibility based on X-ray assays. In particular, the hydrogel offers the clinically important advantage of visibility in CT and T2-weighted magnetic resonance imaging. Based on the results of the current study, the SF/AU composite hydrogel may offer several advantages for future application in nucleus pulposus replacement.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16

Similar content being viewed by others

References

  1. Andersson GB. Epidemiological features of chronic low-back pain. Lancet. 1999;354(9178):581–5.

    Article  CAS  Google Scholar 

  2. Leino PI, Berg MA, Puska P. Is back pain increasing? Results from national surveys in Finland during 1978/9–1992. Scand J Rheumatol. 1994;23(5):269–76.

    Article  CAS  Google Scholar 

  3. Bressler HB, Keyes WJ, Rochon PA, Badley E. The prevalence of low back pain in the elderly. A systematic review of the literature. Spine (Phila Pa 1976). 1999;24(17):1813–9.

    Article  CAS  Google Scholar 

  4. Ghiselli G, Wang JC, Bhatia NN, Hsu WK, Dawson EG. Adjacent segment degeneration in the lumbar spine. J Bone Joint Surg Am. 2004;86(A7):1497–503.

    Google Scholar 

  5. Phillips FM, Reuben J, Wetzel FT. Intervertebral disc degeneration adjacent to a lumbar fusion. An experimental rabbit model. J Bone Joint Surg Br. 2002;84(2):289–94.

    Article  CAS  Google Scholar 

  6. Hilibrand AS, Robbins M. Adjacent segment degeneration and adjacent segment disease: the consequences of spinal fusion? Spine J. 2004;4(6):190S–4S.

    Article  Google Scholar 

  7. Bao QB, McCullen GM, Higham PA, Dumbleton JH, Yuan HA. The artificial disc: theory, design and materials. Biomaterials. 1996;17(12):1157–67.

    Article  CAS  Google Scholar 

  8. Gillet P. The fate of the adjacent motion segments after lumbar fusion. J Spinal Disord Tech. 2003;16(4):338–45.

    Article  Google Scholar 

  9. Tibrewal SB, Pearcy MJ. Lumbar intervertebral disc heights in normal subjects and patients with disc herniation. Spine. 1985;10(5):452–4.

    Article  CAS  Google Scholar 

  10. Studer A. Nucleus prosthesis: a new concept. EUR Spine J. 2002;11(Suppl 2):S154–6.

    Google Scholar 

  11. Selviaridis P, Foroglou N, Tsitlakidis A, Hatzisotiriou A, Magras I, Patsalas I. Long-term outcome after implantation of prosthetic disc nucleus device (PDN) in lumbar disc disease. Hippokratia. 2010;14(3):176–84.

    CAS  Google Scholar 

  12. Joshi A, Massey CJ, Karduna A, Vresilovic E, Marcolongo M. The effect of nucleus implant parameters on the compressive mechanics of the lumbar intervertebral disc: a finite element study. J Biomed Mater Res B Appl Biomater. 2009;90(2):596–607.

    Google Scholar 

  13. Thomas J, Lowman A, Marcolongo M. Novel associated hydrogels for nucleus pulposus replacement. J Biomed Mater Res A. 2003;67(4):1329–37.

    Article  Google Scholar 

  14. Allen MJ, Schoonmaker JE, Bauer TW, Williams PF, Higham PA, Yuan HA. Preclinical evaluation of a poly (vinyl alcohol) hydrogel implant as a replacement for the nucleus pulposus. Spine (Phila Pa 1976). 2004;29(5):515–23.

    Article  Google Scholar 

  15. Joshi A, Fussell G, Thomas J, Hsuan A, Lowman A, Karduna A, Vresilovic E, Marcolongo M. Functional compressive mechanics of a PVA/PVP nucleus pulposus replacement. Biomaterials. 2006;27(2):176–84.

    Article  CAS  Google Scholar 

  16. Thomas JD, Fussell G, Sarkar S, Lowman AM, Marcolongo M. Synthesis and recovery characteristics of branched and grafted PNIPAAm-PEG hydrogels for the development of an injectable load-bearing nucleus pulposus replacement. Acta Biomater. 2010;6(4):1319–28.

    Article  CAS  Google Scholar 

  17. Bergknut N, Smolders LA, Koole LH, Voorhout G, Hagman RE, Lagerstedt AS, Saralidze K, Hazewinkel HA, van der Veen AJ, Meij BP. The performance of a hydrogel nucleus pulposus prosthesis in an ex vivo canine model. Biomaterials. 2010;31(26):6782–8.

    Article  CAS  Google Scholar 

  18. Boelen EJ, Koole LH, van Rhijn LW, van Hooy-Corstjens CS. Towards a functional radiopaque hydrogel for nucleus pulposus replacement. J Biomed Mater Res B Appl Biomater. 2007;83(2):440–50.

    Google Scholar 

  19. Boelen EJ, van Hooy-Corstjens CS, Bulstra SK, van Ooij A, van Rhijn LW, Koole LH. Intrinsically radiopaque hydrogels for nucleus pulposus replacement. Biomaterials. 2005;26(33):6674–83.

    Article  CAS  Google Scholar 

  20. Bertagnoli R, Schonmayr R. Surgical and clinical results with the PDN prosthetic disc-nucleus device. Eur Spine J. 2002;11(Suppl 2):S143–8.

    Google Scholar 

  21. Klara PM, Ray CD. Artificial nucleus replacement: clinical experience. Spine (Phila Pa 1976). 2002;27(12):1374–7.

    Article  Google Scholar 

  22. Jin D, Qu D, Zhao L, Chen J, Jiang J. Prosthetic disc nucleus (PDN) replacement for lumbar disc herniation: preliminary report with six months’ follow-up. J Spinal Disord Tech. 2003;16(4):331–7.

    Article  Google Scholar 

  23. Bertagnoli R, Vazquez RJ. The Anterolateral TransPsoatic Approach (ALPA): a new technique for implanting prosthetic disc-nucleus devices. J Spinal Disord Tech. 2003;16(4):398–404.

    Article  Google Scholar 

  24. Shim CS, Lee SH, Park CW, Choi WC, Choi G, Choi WG, et al. Partial disc replacement with the PDN prosthetic disc nucleus device: early clinical results. J Spinal Disord Tech. 2003;16(4):324–30.

    Article  Google Scholar 

  25. Carl A, Ledet E, Yuan H, Sharan A. New developments in nucleus pulposus replacement technology. Spine J. 2004;4(6):325S–9S.

    Article  Google Scholar 

  26. Korge A, Nydegger T, Polard JL, Mayer HM, Husson JL. A spiral implant as nucleus prosthesis in the lumbar spine. Eur Spine J. 2002;11(2):S149–53.

    Google Scholar 

  27. Meakin JR, Reid JE, Hukins DW. Replacing the nucleus pulposus of the intervertebral disc. Clin Biomech (Bristol, Avon). 2001;16(7):560–5.

    Article  CAS  Google Scholar 

  28. Arthur A, Cannella M, Keane M, Singhatat W, Vresilovic E, Marcolongo M. Fill of the nucleus cavity affects mechanical stability in compression, bending, and torsion of a spine segment, which has undergone nucleus replacement. Spine (Phila Pa 1976). 2010;35(11):1128–35.

    Article  Google Scholar 

  29. Iatridis JC, Weidenbaum M, Setton LA, Mow VC. Is the nucleus pulposus a solid or a fluid? Mechanical behaviours of the nucleus pulposus of the human intervertebral disc. Spine (Phila Pa 1976). 1996;21(10):1174–84.

    Article  CAS  Google Scholar 

  30. Stammen JA, Williams S, Ku DN, Guldberg RE. Mechanical properties of a novel PVA hydrogel in shear and unconfined compression. Biomaterials. 2001;22(8):799–806.

    Article  CAS  Google Scholar 

  31. Bryant SJ, Anseth KS. Controlling the spatial distribution of ECM components in degradable PEG hydrogels for tissue engineering cartilage. J Biomed Mater Res. 2003;64A:70–9.

    Article  CAS  Google Scholar 

  32. Hutmacher DW, Ng KW, Kaps C, Sittinger M, Klaring S. Elastic cartilage engineering using novel scaffold architectures in combination with a biomimetic cell carrier. Biomaterials. 2003;24:4445–58.

    Article  CAS  Google Scholar 

  33. Fagan MJ, Julian S, Siddall DJ, Mohsen AM. Patient-specific spine models. Part 1: Finite element analysis of the lumbar intervertebral disc—a material sensitivity study. Proc Inst Mech Eng H. 2002;216(5):299–314.

    Article  CAS  Google Scholar 

  34. Meakin JR. Replacing the nucleus pulposus of the intervertebral disk: prediction of suitable properties of a replacement material using finite element analysis. J Mater Sci Mater Med. 2001;12(3):207–13.

    Article  CAS  Google Scholar 

  35. Setton LA, Mow VC, Howell DS. Mechanical behaviour of articular cartilage in shear is altered by transection of the anterior cruciate ligament. J Orthop Res. 1995;13(4):473–82.

    Article  CAS  Google Scholar 

  36. Nettles DL, Vail TP, Morgan MT, Grinstaff MW, Setton LA. Photocrosslinkable hyaluronan as a scaffold for articular cartilage repair. Annu Rev Biomed Eng. 2004;32(3):391–7.

    Article  Google Scholar 

  37. LeRoux MA, Guilak F, Setton LA. Compressive and shear properties of alginate gel: effects of sodium ions and alginate concentration. J Biomed Mater Res. 1999;47(1):46–53.

    Article  CAS  Google Scholar 

  38. Trabbic-Carlson K, Setton LA, Chilkoti A. Swelling and mechanical behaviours of chemically cross-linked hydrogels of elastin-like polypeptides. Biomacromolecules. 2003;4(3):572–80.

    Article  CAS  Google Scholar 

  39. Leone G, Torricelli P, Chiumiento A, Facchini A, Barbucci R. Amidic alginate hydrogel for nucleus pulposus replacement. J Biomed Mater Res A. 2007;84(2):391–401.

    Google Scholar 

  40. Su WY, Chen YC, Lin FH. Injectable oxidized hyaluronic acid/adipic acid dihydrazide hydrogel for nucleus pulposus regeneration. Acta Biomater. 2010;6(8):3044–55.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Mr. Chen Han-Ming for SEM imaging, Mr. Chenlongkun for assistance with the MTT test. This work was supported by the science and technology department of Zhejiang province (491010-j30987).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiangjin Lin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hu, J., Chen, B., Guo, F. et al. Injectable silk fibroin/polyurethane composite hydrogel for nucleus pulposus replacement. J Mater Sci: Mater Med 23, 711–722 (2012). https://doi.org/10.1007/s10856-011-4533-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-011-4533-y

Keywords

Navigation