Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications

Abstract

Hyaluronic acid (hyaluronan, HA) is a linear polysaccharide formed from disaccharide units containing N-acetyl-d-glucosamine and glucuronic acid. It has a high molecular mass, usually in the order of millions of Daltons, and interesting viscoelastic properties influenced by its polymeric and polyelectrolyte characteristics. HA is present in almost all biological fluids and tissues. In clinical medicine, it is used as a diagnostic marker for many diseases including cancer, rheumatoid arthritis and liver pathologies, as well as for supplementation of impaired synovial fluid in arthritic patients by means of intra-articular injections. It is also used in certain ophthalmological and otological surgeries and cosmetic regeneration and reconstruction of soft tissue. Herein we present an overview of the occurrence and physiological properties of HA, as well as of the recent advances in production biotechnology and preparation of the HA-based materials for medical application.

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

Fig. 1

References

  1. Amarnath LP, Srinivas A, Ramamurthi A (2006) In vitro hemocompatibility testing of UV-modified hyaluronan hydrogels. Biomaterials 27:1416–1424

    Article  CAS  PubMed  Google Scholar 

  2. Balazs EA (2004) Viscoelastic properties of hyaluronan and its therapeutic use. In: Garg HG, Hales CA (eds) Chemistry and biology of hyaluronan. Elsevier, Amsterdam, p 415

  3. Balazs EA, Denlinger JL (1989) Clinical uses of hyaluronan. Ciba Found Symp 143:265–275

    CAS  PubMed  Google Scholar 

  4. Barbucci R, Lamponi S, Borzacchiello A, Ambrosio L, Fini M, Torricelli P, Giardino R (2002) Hyaluronic acid hydrogel in the treatment of osteoarthritis. Biomaterials 23:4503–4513

    Article  CAS  PubMed  Google Scholar 

  5. Butler JE, Hammond TH, Gray SD (2001) Gender-related differences of hyaluronic acid distribution in the human vocal fold. Laryngoscope 111:907–911

    Article  CAS  PubMed  Google Scholar 

  6. Camenisch TD, McDonald JA (2000) Hyaluronan: is bigger better? Am J Respir Cell Mol Biol 23:431–433

    CAS  PubMed  Google Scholar 

  7. Chan RW, Gray SD, Titze IR (2001) The importance of hyaluronic acid in vocal fold biomechanics. Otolaryngol Head Neck Surg 124:607–614

    Article  CAS  PubMed  Google Scholar 

  8. Chong BF, Blank LM, McLaughlin R, Nielsen L (2005) Microbial hyaluronic acid production. Appl Microbiol Biotechnol 66:341–351

    Article  CAS  PubMed  Google Scholar 

  9. Edmonds ME, Foster AV (2006) Diabetic foot ulcers. Brit Med J 332:407–410

    Article  PubMed  Google Scholar 

  10. Esposito E, Menegatti E, Cortesi R (2005) Hyaluronan-based microspheres as tools for drug delivery: a comparative study. Int J Pharm 288:35–49

    Article  CAS  PubMed  Google Scholar 

  11. Evanko S, Wight T (2001) Intracellular hyaluronan. In: Hyaluronan: synthesis, function, catabolism. Available at http://www.glycoforum.gr.jp/science/hyaluronan/HA20/HA20E.html. Cited 30 Jul 2001

  12. Evanich JD, Evanich CJ, Wright MB, Rydlewicz JA (2001) Efficacy of intraarticular hyaluronic acid injections in knee osteoarthritis. Clin Orthop 390:173–181

    PubMed  Google Scholar 

  13. Garg HG, Hales CA (eds) (2004) Chemistry and biology of hyaluronan. Elsevier, Amsterdam

  14. Greenberg DD, Stoker A, Kane S, Cockrell M, Cook JL (2006) Biochemical effects of two different hyaluronic acid products in a co-culture model of osteoarthritis. Osteoarthr Cartil 14:814–822

    Article  CAS  PubMed  Google Scholar 

  15. Hertegard S, Hallen L, Laurent C, Lindstrom E, Olofsson K, Testad P, Dahlqvist A (2002) Cross-linked hyaluronan used as augmentation substance for treatment of glottal insufficiency: safety aspects and vocal fold function. Laryngoscope 112:2211–2219

    Article  PubMed  Google Scholar 

  16. Juhlin L (1997) Hyaluronan in skin. J Intern Med 242:61–66

    Article  CAS  PubMed  Google Scholar 

  17. Kanchwala SK, Holloway L, Bucky LP (2005) Reliable soft tissue augmentation: a clinical comparison of injectable soft-tissue fillers for facial-volume augmentation. Ann Plast Surg 55:30–35

    Article  PubMed  Google Scholar 

  18. Kogan G, Šoltés L, Stern R, Schiller J, Mendichi R (2006) Hyaluronic acid: its function and degradation in in vivo systems. In: Atta-ur-Rahman (ed) Studies in natural products chemistry (vol 35, Bioactive natural products, Part D). Elsevier, Amsterdam (in press)

  19. Laurent TC (1998) The chemistry, biology and medical applications of hyaluronan and its derivatives. Portland Press, London

    Google Scholar 

  20. Maltese A, Borzacchiello A, Mayol L, Bucolo C, Maugeri F, Nicolais L, Ambrosio L (2006) Novel polysaccharides-based viscoelastic formulations for ophthalmic surgery: rheological characterization. Biomaterials 27:5134–5142

    Article  CAS  PubMed  Google Scholar 

  21. Manna F, Dentini M, Desideri P, De Pitá O, Mortilla E, Maras B (1999) Comparative chemical evaluation of two commercially available derivatives of hyaluronic acid (Hylaform® from rooster combs and Restylane® from Streptococcus) used for soft tissue augmentation. J Eur Acad Dermatol Venereol 13:183–192

    CAS  PubMed  Google Scholar 

  22. Mendichi R, Schieroni AG (2002) Fractionation and characterization of ultra-high molar mass hyaluronan: 2. On-line size exclusion chromatography methods. Polymer 43:6115–6121

    Article  CAS  Google Scholar 

  23. Mendichi R, Šoltés L (2002) Hyaluronan molecular weight and polydispersity in some commercial intra-articular injectable preparations and in synovial fluid. Inflamm Res 51:115–116

    Article  CAS  Google Scholar 

  24. Miyazaki T, Yomota C, Okada S (1998) Degradation of hyaluronic acid at the metal surface. Colloid Polym Sci 276:388–394

    Article  CAS  Google Scholar 

  25. Moseley R, Walker M, Waddington RJ, Chen WYJ (2003) Comparison of the antioxidant properties of wound dressing materials—carboxymethylcellulose, hyaluronan benzyl ester and hyaluronan, towards polymorphonuclear leukocyte-derived reactive oxygen species. Biomaterials 24:1549–1557

    Article  CAS  PubMed  Google Scholar 

  26. Narins RS, Brandt F, Leyden J, Lorenc ZP, Rubin M, Smith S (2003) A randomized, double-blind, multicenter comparison of the efficacy and tolerability of Restylane versus Zyplast for the correction of nasolabial folds. Dermatol Surg 29:588–595

    Article  PubMed  Google Scholar 

  27. Prehm P (2000) Hyaluronan. In: Vandamme EJ, De Baets S, Steinbüchel A (eds) Biopolymers: biology, chemistry, biotechnology, applications, vol 5, Polysaccharides I. Polysaccharides from prokaryotes. Wiley-VCH, Weinheim, pp 379–404

  28. Schiller J, Fuchs B, Arnhold J, Arnold K (2003) Contribution of reactive oxygen species to cartilage degradation in rheumatic diseases: molecular pathways, diagnosis and potential therapeutic strategies. Curr Med Chem 10:2123–2145

    Article  CAS  PubMed  Google Scholar 

  29. Shiedlin A, Bigelow R, Christopher W, Arbabi S, Yang L, Maier RV, Wainwright N, Childs A, Miller RJ (2004) Evaluation of hyaluronan from different sources: Streptococcus zooepidemicus, rooster comb, bovine vitreous, and human umbilical cord. Biomacromolecules 5:2122–2127

    Article  CAS  PubMed  Google Scholar 

  30. Shu XZ, Liu Y, Palumbo1 FS, Luo Y, Prestwich GD (2004) In situ crosslinkable hyaluronan hydrogels for tissue engineering. Biomaterials 25:1339–1348

    Article  CAS  Google Scholar 

  31. Šoltés L, Mendichi R (2003) Molecular characterization of two host–guest associating hyaluronan derivatives. Biomed Chromatogr 17:376–384

    Article  PubMed  Google Scholar 

  32. Šoltés L, Mendichi R, Kogan G, Schiller J, Stankovská M, Arnhold J (2006) Degradative action of reactive oxygen species on hyaluronan. Biomacromolecules 7:659–668

    Article  PubMed  Google Scholar 

  33. Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85:699–715

    Article  CAS  PubMed  Google Scholar 

  34. Tammi MI, Day AJ, Turley EA (2002) Hyaluronan and homeostasis: a balancing act. J Biol Chem 277:4581–4784

    Article  CAS  PubMed  Google Scholar 

  35. Turner NJ, Kielty CM, Walker MG, Canfield AE (2004) A novel hyaluronan-based biomaterial (Hyaff-11®) as a scaffold for endothelial cells in tissue engineered vascular grafts. Biomaterials 25:5955–5964

    Article  CAS  PubMed  Google Scholar 

  36. Vasiliu S, Popa M, Rinaudo M (2005) Polyelectrolyte capsules made of two biocompatible natural polymers. Eur Polym J 41:923–932

    Article  CAS  Google Scholar 

  37. Ward PD, Thibeault SL, Gray SD (2002) Hyaluronic acid: its role in voice. J Voice 16:303–309

    Article  PubMed  Google Scholar 

  38. Widner B, Behr R, von Dollen S, Tang M, Heu T, Sloma A, Sternberg D, De Angelis PL, Weigel PH, Brown S (2005) Hyaluronic acid production in Bacillus subtilis. Appl Env Microbiol 71:3747–3752

    Article  CAS  Google Scholar 

  39. Xu H, Ito T, Tawada A, Maeda H, Yamanokuchi H, Isahara K, Yoshida K, Uchiyama Y, Asari A (2002) Effect of hyaluronan oligosaccharides on the expression of heat shock protein 72. J Biol Chem 277:17308–17314

    Article  CAS  PubMed  Google Scholar 

  40. Yun YH, Goetz DJ, Yellen P, Chen W (2004) Hyaluronan microspheres for sustained gene delivery and site-specific targeting. Biomaterials 25:147–157

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Slovak Research and Development Agency under the contract APVV-51-033205 and Agency for Science VEGA of the Slovak Academy of Sciences and Ministry of Education of Slovak Republic, grants 1/4452/07, 2/4143/26, and 2/5002/5, and by Center of Excellence CEDEBIPO of the Slovak Academy of Sciences.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Grigorij Kogan.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kogan, G., Šoltés, L., Stern, R. et al. Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications. Biotechnol Lett 29, 17–25 (2007). https://doi.org/10.1007/s10529-006-9219-z

Download citation

Keywords

  • Arthritis
  • Degradation
  • Hyaluronan
  • Reactive oxygen species
  • Tissue regeneration
  • Viscosity