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.
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References
Amarnath LP, Srinivas A, Ramamurthi A (2006) In vitro hemocompatibility testing of UV-modified hyaluronan hydrogels. Biomaterials 27:1416–1424
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
Balazs EA, Denlinger JL (1989) Clinical uses of hyaluronan. Ciba Found Symp 143:265–275
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
Butler JE, Hammond TH, Gray SD (2001) Gender-related differences of hyaluronic acid distribution in the human vocal fold. Laryngoscope 111:907–911
Camenisch TD, McDonald JA (2000) Hyaluronan: is bigger better? Am J Respir Cell Mol Biol 23:431–433
Chan RW, Gray SD, Titze IR (2001) The importance of hyaluronic acid in vocal fold biomechanics. Otolaryngol Head Neck Surg 124:607–614
Chong BF, Blank LM, McLaughlin R, Nielsen L (2005) Microbial hyaluronic acid production. Appl Microbiol Biotechnol 66:341–351
Edmonds ME, Foster AV (2006) Diabetic foot ulcers. Brit Med J 332:407–410
Esposito E, Menegatti E, Cortesi R (2005) Hyaluronan-based microspheres as tools for drug delivery: a comparative study. Int J Pharm 288:35–49
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
Evanich JD, Evanich CJ, Wright MB, Rydlewicz JA (2001) Efficacy of intraarticular hyaluronic acid injections in knee osteoarthritis. Clin Orthop 390:173–181
Garg HG, Hales CA (eds) (2004) Chemistry and biology of hyaluronan. Elsevier, Amsterdam
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
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
Juhlin L (1997) Hyaluronan in skin. J Intern Med 242:61–66
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
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)
Laurent TC (1998) The chemistry, biology and medical applications of hyaluronan and its derivatives. Portland Press, London
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
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
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
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
Miyazaki T, Yomota C, Okada S (1998) Degradation of hyaluronic acid at the metal surface. Colloid Polym Sci 276:388–394
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
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
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
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
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
Shu XZ, Liu Y, Palumbo1 FS, Luo Y, Prestwich GD (2004) In situ crosslinkable hyaluronan hydrogels for tissue engineering. Biomaterials 25:1339–1348
Šoltés L, Mendichi R (2003) Molecular characterization of two host–guest associating hyaluronan derivatives. Biomed Chromatogr 17:376–384
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
Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85:699–715
Tammi MI, Day AJ, Turley EA (2002) Hyaluronan and homeostasis: a balancing act. J Biol Chem 277:4581–4784
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
Vasiliu S, Popa M, Rinaudo M (2005) Polyelectrolyte capsules made of two biocompatible natural polymers. Eur Polym J 41:923–932
Ward PD, Thibeault SL, Gray SD (2002) Hyaluronic acid: its role in voice. J Voice 16:303–309
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
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
Yun YH, Goetz DJ, Yellen P, Chen W (2004) Hyaluronan microspheres for sustained gene delivery and site-specific targeting. Biomaterials 25:147–157
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.
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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
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DOI: https://doi.org/10.1007/s10529-006-9219-z