Skip to main content
Log in

Physical properties of crosslinked hyaluronic acid hydrogels

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

Abstract

In order to improve the mechanical properties and control the degradation rate of hyaluronic acid (HA) an investigation of the structural and mechanical properties of the hydrogels crosslinked using divinyl sulfone (DVS), glutaraldehyde (GTA) and freeze-thawing, or autocrosslinking has been carried out. The thermal and mechanical properties of the gels were characterised by differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and compression tests. The solution degradation products of each system have been analysed using size exclusion chromatography (SEC) and the Zimm–Stockmayer theory applied. Autocrosslinked gels swell the most quickly, whereas the GTA crosslinked gels swell most slowly. The stability of the autocrosslinked gels improves with a reduction in solution pH, but is still poor. GTA and DVS crosslinked gels are robust and elastic when water swollen, with glass transition values around 20°C. SEC results show that the water soluble degradation products of the gels show a reduction in the radius of gyration at any particular molecular weight and this is interpreted as indicating increased hydrophobicity arising from chemical modification.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Similar content being viewed by others

References

  1. A. Lowman, N. Peppas, Hydrogels, in Encyclopedia of Controlled Drug Delivery, ed. by E. Mathiowitz (New York, Wiley, 1999), pp. 397–418

    Google Scholar 

  2. J.H. deGoot et al., Meniscal tissue regeneration in porous 50/50 copoly(l-lactide/caprolactone) implants. Biomaterials 18(8):613–622 (1997)

    Google Scholar 

  3. D. Ingber et al., Chapter 2. in Physical Forces and the Mammalian Cell. (Academic Press, New York, 1993)

  4. L. Lapcik, et al., Hyaluronan: preparation, styructure, properties and applications. Chem. Rev. 98(8), 2663–2684 (1998)

    Article  CAS  Google Scholar 

  5. W.Y. Chen, G. Abatangelo, Functions of hyaluronan in wound repair. Wound Repair Regen. 7, 79–89 (1999)

    Google Scholar 

  6. E.A. Turley, P.W. Nobel, Signalling properties of hyaluronan receptors. J. Biol. Chem. 277, 4589–4592 (2002)

    Article  CAS  Google Scholar 

  7. F.S. Palumbo, et al., New graft copolymers of hyaluronic acid and polylactic acid: synthesis and characterization. Carbohydr. Polym. 66(3), 379–385 (2006)

    Article  CAS  Google Scholar 

  8. S.-N. Park et al., Biological characterization of EDC-crosslinked collagen–hyaluronic acid matrix in dermal tissue restoration. Biomaterials 24(9), 1631–1641 (2003)

    Google Scholar 

  9. J. Leach, et al., Photocrosslinked hyaluronic acid hydrogels: natural, biodegradable tissue engineering scaffolds. Biotechnol. Bioeng. 82(5), 578–589 (2003)

    Article  CAS  Google Scholar 

  10. T.C. Laurent (ed.), The Chemistry, Biology and Medical Applcations of Hyaluronan and its Derivatives. Wenner-Gren International Series, vol. 72 (Portland Press Ltd, London, 1998)

  11. J.C. Fernandez Lopez, A. Ruano-Ravina, Efficacy and safety of intraarticular hyaluronic acid in the treatment of hip osteoarthritis: a systematic review. Osteoarth. Cart. 14(12), 1306–1311 (2006)

    Article  CAS  Google Scholar 

  12. R. Barbucci et al., Hyaluronic acid hydrogel in the treatment of osteoarthritis. Biomaterials 23(23), 4503–4513 (2002)

    Google Scholar 

  13. E. Balazs, in Sodium Hyaluronate and Viscosurgery. Meds. Healon (Sodium Hyaluronate). A Guide to Its Use in Ophthalmic Surgery, ed. by D. Miller, R. Stegmann (Wiley, New York, 1983), pp. 5–28

  14. E. Turley, RHAMM, a Member of the Hyaladherins. in The Science of Hyaluronan Today. 1999 http://www.glycoforum.gr.jp/index.htm

  15. L. Huang, et al., Engineered collagen-PEO nanofibrils and fabrics. J. Biomat. Sci.: Polym. Ed. 12, 979–993 (2001)

    Article  CAS  Google Scholar 

  16. O. Oksala, et al., Expression of proteoglycans and hyaluronan during wound healing. J. Histochem. Cytochem. 43(2), 125–135 (1995)

    CAS  Google Scholar 

  17. K. Fukuda, et al., Hyaluronic acid inhibits interleukin-1-induced superoxide anion in bovine chondrocytes. Inflamm. Res. 46(3), 114–117 (1997)

    Article  CAS  Google Scholar 

  18. K. Tomihata, Y. Ikada, Crosslinking of hyaluronic acid with glutaraldehyde. J. Polym. Sci. A: Polym. Chem. 35, 3553–3559 (1997)

    Article  CAS  Google Scholar 

  19. K. Tomihata, Y. Ikada, Preparation of crosslinked hyaluronic acid films of low water content. Biomaterials 18(3), 189–195 (1997)

    Article  CAS  Google Scholar 

  20. K. Tomihata, Y. Ikada, Crosslinking of hyaluronic acid with water soluble carbodiimide. J. Biomed. Mater. Res. 37, 243–251 (1997)

    Article  CAS  Google Scholar 

  21. M.N. Collins, C. Birkinshaw, Comparison of the effectiveness of four different crosslinking agents with hyaluronic acid hydrogel films for tissue-culture applications. J. Appl. Polym. Sci. 104, 3183–3191 (2007)

    Article  CAS  Google Scholar 

  22. M.N. Collins, C. Birkinshaw, Investigation of the swelling behaviour of crosslinked hyaluronic acid films and hydro-gels produced using homogeneous reactions. J. Appl. Polym. Sci. 109, 923–931 (2008)

    Article  CAS  Google Scholar 

  23. A. Okamoto, T. Miyoshi, A Biocompatible gel of Hyaluronan. in Hyaluronan, ed. by J. Kennedy, G. Phillips, P. Williams (Woodhead Publishing Limited, Cambridge, 2002)

  24. J. Bracke, K. Thacker, Hyaluronic Acid from Bacterial Culture (Diagnostic Inc, Minneapolis, MN, USA, 1985)

    Google Scholar 

  25. J.W. Burns, S. Cox, A. Walts, In United States Patent 5,017,229 (Genzyme Corporation, Cambridge, MA, USA, 1991)

  26. J. Roovers, Branched Polymers, in Encylopedia of Polymer Science & Eng., vol. 2 (John Wiley, 1985), pp. 478–499

  27. S. Grcev, P. Schoenmakers, P. Iedema, Determination of molecular weight and size distribution and branching characteristics of PVAc by means of size exclusion chromatography/multi-angle laser light scattering (SEC/MALLS). Polymer 45, 39–48 (2004)

    Article  CAS  Google Scholar 

  28. M.N. Collins, in Fabrication of Porous Scaffolds for Tissue Engineering. PhD thesis (University of Limerick, 2007)

  29. S.A. Bencherif, A. Srinivasan, F. Horkay, J.O. Hollinger, K. Matyjaszewski, N.R. Washburn, Influence of the degree of methacrylation on hyaluronic acid hydrogels properties. Biomaterials 29, 1739–1749 (2008)

    Article  CAS  Google Scholar 

  30. K.P.Menard, Dynamic Mechanical Analysis Basics: Part 2 Thermoplastic Transitions and Properties. Perkin Elmer: Application Note (1999)

  31. K. Kirker, G. Prestwich, Physical properties of glycosaminoglycan hydrogels. J. Polym. Sci. B: Polym. Phys. 42, 4344–4356 (2004)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maurice N. Collins.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Collins, M.N., Birkinshaw, C. Physical properties of crosslinked hyaluronic acid hydrogels. J Mater Sci: Mater Med 19, 3335–3343 (2008). https://doi.org/10.1007/s10856-008-3476-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-008-3476-4

Keywords

Navigation