Skip to main content
SpringerLink
Log in

Rheological study of hyaluronic acid derivatives

  • Original Article
  • Published:
Biomedical Engineering Letters Aims and scope Submit manuscript

Abstract

The viscoelastic properties of four novel, low molecular weight hyaluronic acid derivatives were investigated and compared to the parent hyaluronic acid compound. Briefly, all derivatives were synthesized by first deacetylating the parent hyaluronic acid. One sample was left as such, while two others were reacytelated. The final compound, of particular interest for its anti-inflammatory properties, was butyrylated. The compounds were dissolved in phosphate buffer solution (PBS) and studied at a concentration of 5 mg/mL. Shear thinning behaviour was observed for all compounds, however, derivative samples had a lower viscosity than the parent compound at high shear rates. Viscoelastic properties were also observed to decrease as a result of the derivative preparation method. It is believed that these changes are primarily caused by a decrease in hyaluronic acid molecular weight. By increasing the concentration of the anti-inflammatory compound, it may be possible to modulate the viscoelastic properties to more closely resemble those of commercial viscosupplements. As a result, an anti-inflammatory derivative of hyaluronic acid may potentially improve upon existing viscosupplements used to treat patients who are susceptible to flare up.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Johnson VL, Hunter DJ. The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol. 2014;28(1):5–15.

    Article  Google Scholar 

  2. Goudoulas TB, Kastrinakis EG, Nychas SG, Papazoglou LG, Kazakos GM, Kosmas PV. Rheological study of synovial fluid obtained from dogs: healthy, pathological, and post-surgery, after spontaneous rupture of cranial cruciate ligament. Ann Biomed Eng. 2010;38(1):57–65.

    Article  Google Scholar 

  3. Jay GD, Torres JR, Warman ML, Laderer MC, Breuer KS. The role of lubricin in the mechanical behavior of synovial fluid. Proc Natl Acad Sci. 2007;104(15):6194–9.

    Article  Google Scholar 

  4. Wobig M, Bach G, Beks P, Dickhut A, Runzheimer J, Schwieger G, Vetter G, Balazs E. The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan g-f 20 and a lower-molecular-weight hyaluronan. Clin Ther. 1999;21(9):1549–62.

    Article  Google Scholar 

  5. Fam H, Kontopoulou M, Bryant JT. Effect of concentration and molecular weight on the rheology of hyaluronic acid/bovine calf serum solutions. Biorheology. 2009;46(1):31–43.

    Google Scholar 

  6. Ludwig TE, McAllister JR, Lun V, Wiley JP, Schmidt TA. Diminished cartilage-lubricating ability of human osteoarthritic synovial fluid deficient in proteoglycan 4: restoration through proteoglycan 4 supplementation. Arthr Rheum. 2012;64(12):3963–71.

    Article  Google Scholar 

  7. Neogi T, Zhang Y. Epidemiology of osteoarthritis. Rheum Dis Clin N Am. 2013;39(1):1–19 (Update on Osteoarthritis).

    Article  Google Scholar 

  8. Schmidt TA, Gastelum NS, Nguyen QT, Schumacher BL, Sah RL. Boundary lubrication of articular cartilage: role of synovial fluid constituents. Arthritis Rheum. 2007;56(3):882–91.

    Article  Google Scholar 

  9. Mensitieri M, Ambrosio L, Iannace S, Nicolais L, Perbellini A. Viscoelastic evaluation of different knee osteoarthritis therapies. J Mater Sci Mater Med. 1995;6(3):130–7.

    Article  Google Scholar 

  10. Choi SC, Ae Yoo M, Lee SY, Lee HJ, Son DH, Jung J, Noh I, Kim CW. Modulation of biomechanical properties of hyaluronic acid hydrogels by crosslinking agents. J Biomed Mater Res A. 2015;103(9):3072–80.

    Article  Google Scholar 

  11. Finelli I, Chiessi E, Galesso D, Renier D, Paradossi G. A new viscosupplement based on partially hydrophobic hyaluronic acid: a comparative study. Biorheology. 2011;48(5–6):263–75.

    Google Scholar 

  12. Shimojo AAM, Pires AMB, Lichy R, Rodrigues AA, Santana MHA. The crosslinking degree controls the mechanical, rheological, and swelling properties of hyaluronic acid microparticles. J Biomed Mater Res A. 2015;103(2):730–7.

    Article  Google Scholar 

  13. Fakhari A, Phan Q, Thakkar SV, Middaugh CR, Berkland C. Hyaluronic acid nanoparticles titrate the viscoelastic properties of viscosupplements. Langmuir. 2013;29(17):5123–31.

    Article  Google Scholar 

  14. Casuso P, Perez-San Vicente A, Iribar H, Gutierrez-Rivera A, Izeta A, Loinaz I, Cabanero G, Grande H-J, Odriozola I, Dupin D. Aurophilically cross-linked “dynamic” hydrogels mimicking healthy synovial fluid properties. Chem Commun. 2014;50:15199–201.

    Article  Google Scholar 

  15. Conrozier T, Mathieu P, Rinaudo M. Mannitol preserves the viscoelastic properties of hyaluronic acid in an in vitro model of oxidative stress. Rheumatol Ther. 2014;1(1):45–54.

    Article  Google Scholar 

  16. Babasola O, Rees-Milton KJ, Bebe S, Wang J, Anastassiades TP. Chemically modified n-acylated hyaluronan fragments modulate proinflammatory cytokine production by stimulated human macrophages. J Biol Chem. 2014;289(36):24779–91.

    Article  Google Scholar 

  17. Campo GM, Avenoso A, Campo S, D’Ascola A, Nastasi G, Calatroni A. Molecular size hyaluronan differently modulates toll-like receptor-4 in LPS-induced inammation in mouse chondrocytes. Biochimie. 2010;92(2):204–15.

    Article  Google Scholar 

  18. Campo GM, Avenoso A, Campo S, D’Ascola A, Nastasi G, Calatroni A. Small hyaluronan oligosaccharides induce inammation by engaging both toll-like-4 and CD44 receptors in human chondrocytes. Biochem Pharmacol. 2010;80(4):480–90.

    Article  Google Scholar 

  19. Mezger TG (2006) “The Rheology handbook”. Vincentz Network, Hannover

  20. Bhuanantanondh P, Grecov D, Kwok E. Rheological study of viscosupplements and synovial fluid in patients with osteoarthritis. J Med Biol Eng. 2012;32(1):12–6.

    Article  Google Scholar 

  21. Mazzucco D, McKinley G, Scott RD, Spector M. Rheology of joint fluid in total knee arthroplasty patients. J Orthop Res. 2002;20(6):1157–63.

    Article  Google Scholar 

  22. Conrozier T, Balblanc J-C, Piperno M, Rinaudo M. Differences in the osteoarthritic synovial fluid composition and rheology between patients with or without are-up. A pilot study. Osteoarthr Cartil. 2012;20:S244.

    Article  Google Scholar 

  23. Maleki A, Kjoniksen AL, Nystrom B. Anomalous viscosity behavior in aqueous solutions of hyaluronic acid. Polym Bull. 2007;59(2):217–26.

    Article  Google Scholar 

  24. Aggarwal A, Sempowski IP. Hyaluronic acid injections for knee osteoarthritis. Systematic review of the literature. Can Fam Phys. 2004;50(2):249–56.

    Google Scholar 

  25. Bhuanantanondh P. Rheology of synovial fluid with and without viscosupplements in patients with osteoarthritis: a pilot study. Master’s thesis, University of British Columbia; 2009.

  26. Neustadt D, Caldwell J, Bell M, Wade J, Gimbel J. Clinical effects of intraarticular injection of high molecular weight hyaluronan (orthovisc) in osteoarthritis of the knee: a randomized, controlled, multicenter trial. J Rheumatol. 2005;32(10):1928–36.

    Google Scholar 

Download references

Acknowledgements

Support from the Canada Foundation for Innovation grant for rheometer purchase is acknowledged. Financial support from the Natural Sciences and Engineering Research Council of Canada, Discovery Grant, is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, BC, Canada

    Michael Chernos & Ezra Kwok

  2. Department of Mechanical Engineering, University of British Columbia, Vancouver, BC, Canada

    Dana Grecov

  3. Department of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada

    Michael Chernos, Dana Grecov & Ezra Kwok

  4. Division of Rheumatology, and of Biomedical and Molecular Sciences, Department of Medicine, Queen’s University, Kingston, ON, Canada

    Siziwe Bebe, Oladunni Babsola & Tassos Anastassiades

Authors
  1. Michael Chernos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dana Grecov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ezra Kwok
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Siziwe Bebe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Oladunni Babsola
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tassos Anastassiades
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dana Grecov.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflict of interest in relation to the work in this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chernos, M., Grecov, D., Kwok, E. et al. Rheological study of hyaluronic acid derivatives. Biomed. Eng. Lett. 7, 17–24 (2017). https://doi.org/10.1007/s13534-017-0010-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13534-017-0010-y

Keywords

Search

Navigation