Biotechnology Letters

, Volume 29, Issue 1, pp 17–25 | Cite as

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

  • Grigorij Kogan
  • Ladislav Šoltés
  • Robert Stern
  • Peter Gemeiner
Review

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.

Keywords

Arthritis Degradation Hyaluronan Reactive oxygen species Tissue regeneration Viscosity 

Notes

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.

References

  1. Amarnath LP, Srinivas A, Ramamurthi A (2006) In vitro hemocompatibility testing of UV-modified hyaluronan hydrogels. Biomaterials 27:1416–1424CrossRefPubMedGoogle 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 415Google Scholar
  3. Balazs EA, Denlinger JL (1989) Clinical uses of hyaluronan. Ciba Found Symp 143:265–275PubMedGoogle 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 23:4503–4513CrossRefPubMedGoogle Scholar
  5. Butler JE, Hammond TH, Gray SD (2001) Gender-related differences of hyaluronic acid distribution in the human vocal fold. Laryngoscope 111:907–911CrossRefPubMedGoogle Scholar
  6. Camenisch TD, McDonald JA (2000) Hyaluronan: is bigger better? Am J Respir Cell Mol Biol 23:431–433PubMedGoogle Scholar
  7. Chan RW, Gray SD, Titze IR (2001) The importance of hyaluronic acid in vocal fold biomechanics. Otolaryngol Head Neck Surg 124:607–614CrossRefPubMedGoogle Scholar
  8. Chong BF, Blank LM, McLaughlin R, Nielsen L (2005) Microbial hyaluronic acid production. Appl Microbiol Biotechnol 66:341–351CrossRefPubMedGoogle Scholar
  9. Edmonds ME, Foster AV (2006) Diabetic foot ulcers. Brit Med J 332:407–410CrossRefPubMedGoogle Scholar
  10. Esposito E, Menegatti E, Cortesi R (2005) Hyaluronan-based microspheres as tools for drug delivery: a comparative study. Int J Pharm 288:35–49CrossRefPubMedGoogle 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 390:173–181PubMedGoogle Scholar
  13. Garg HG, Hales CA (eds) (2004) Chemistry and biology of hyaluronan. Elsevier, AmsterdamGoogle Scholar
  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 14:814–822CrossRefPubMedGoogle 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 112:2211–2219CrossRefPubMedGoogle Scholar
  16. Juhlin L (1997) Hyaluronan in skin. J Intern Med 242:61–66CrossRefPubMedGoogle 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 55:30–35CrossRefPubMedGoogle 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)Google Scholar
  19. Laurent TC (1998) The chemistry, biology and medical applications of hyaluronan and its derivatives. Portland Press, LondonGoogle 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 27:5134–5142CrossRefPubMedGoogle 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 13:183–192PubMedGoogle Scholar
  22. Mendichi R, Schieroni AG (2002) Fractionation and characterization of ultra-high molar mass hyaluronan: 2. On-line size exclusion chromatography methods. Polymer 43:6115–6121CrossRefGoogle 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 51:115–116CrossRefGoogle Scholar
  24. Miyazaki T, Yomota C, Okada S (1998) Degradation of hyaluronic acid at the metal surface. Colloid Polym Sci 276:388–394CrossRefGoogle 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 24:1549–1557CrossRefPubMedGoogle 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 29:588–595CrossRefPubMedGoogle 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 379–404Google Scholar
  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 10:2123–2145CrossRefPubMedGoogle 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 5:2122–2127CrossRefPubMedGoogle Scholar
  30. Shu XZ, Liu Y, Palumbo1 FS, Luo Y, Prestwich GD (2004) In situ crosslinkable hyaluronan hydrogels for tissue engineering. Biomaterials 25:1339–1348CrossRefGoogle Scholar
  31. Šoltés L, Mendichi R (2003) Molecular characterization of two host–guest associating hyaluronan derivatives. Biomed Chromatogr 17:376–384CrossRefPubMedGoogle Scholar
  32. Šoltés L, Mendichi R, Kogan G, Schiller J, Stankovská M, Arnhold J (2006) Degradative action of reactive oxygen species on hyaluronan. Biomacromolecules 7:659–668CrossRefPubMedGoogle Scholar
  33. Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85:699–715CrossRefPubMedGoogle Scholar
  34. Tammi MI, Day AJ, Turley EA (2002) Hyaluronan and homeostasis: a balancing act. J Biol Chem 277:4581–4784CrossRefPubMedGoogle 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 25:5955–5964CrossRefPubMedGoogle Scholar
  36. Vasiliu S, Popa M, Rinaudo M (2005) Polyelectrolyte capsules made of two biocompatible natural polymers. Eur Polym J 41:923–932CrossRefGoogle Scholar
  37. Ward PD, Thibeault SL, Gray SD (2002) Hyaluronic acid: its role in voice. J Voice 16:303–309CrossRefPubMedGoogle 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 71:3747–3752CrossRefGoogle 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 277:17308–17314CrossRefPubMedGoogle Scholar
  40. Yun YH, Goetz DJ, Yellen P, Chen W (2004) Hyaluronan microspheres for sustained gene delivery and site-specific targeting. Biomaterials 25:147–157CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Grigorij Kogan
    • 1
  • Ladislav Šoltés
    • 2
  • Robert Stern
    • 3
  • Peter Gemeiner
    • 1
  1. 1.Institute of ChemistrySlovak Academy of SciencesBratislavaSlovakia
  2. 2.Institute of Experimental PharmacologySlovak Academy of SciencesBratislavaSlovakia
  3. 3.Department of Pathology, School of MedicineUniversity of CaliforniaSan FranciscoUSA

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