Glycosaminoglycans – types, structure, functions, and the role in wound healing processes

• Authors: Kinga Orlińska , Katarzyna Komosińska-Vassev , Krystyna Olczyk , Aleksandra Kowalczyk , Paweł Olczyk

Title variants

PL

Glikozoaminoglikany – rodzaje, struktura, funkcje i rola w procesach gojenia ran

• Languages of publication: EN PL

Abstracts

EN

Glycosaminoglycans (GAGs) are a group of heteropolysaccharides, which include: chondroitin sulfates, dermatan sulfates, heparan sulfates, heparin, keratan sulfates, and hyaluronic acid. GAGs are composed of negatively charged polysaccharide chains composed of repeating disaccharide units, which include N-acetylated hexosamine residues – D-glucosamine or D-galactosamine – or N-sulfated D-glucosamine and hexuronic acid residues – D-glucuronic or L-iduronic acid – or galactose. All GAGs, except for hyaluronic acid, have a sulfate group and form proteoglycans (PGs) when attached to the core proteins. GAGs have many important biological functions influencing PGs functions. PGs are present in all types of tissues and participate in cell migration, proliferation, and differentiation. They occur mainly in the extracellular matrix (ECM), where they participate in ECM organization, structure formation and mechanical properties. They play an important role in maintaining homeostasis and also influence metabolic processes, such as bone mineralization and blood coagulation. PGs (due to the strongly negative charge of the glycan chains) are involved in the selective permeability of cell membranes. Components of the ECM, including GAGs, play a structural and functional role during the healing of tissue damage. They regulate the healing process by acting as a reservoir and modulator for cytokines and growth factors and perform structural functions by filling tissue defects during the repair process.

PL

Glikozoaminoglikany (glycosaminoglycans – GAGs) są grupą heteropolisacharydów, w której skład wchodzą: siarczany chondroityny, siarczany dermatanu, siarczany heparanu, heparyny, siarczany keratanu oraz kwas hialuronowy. GAGs zbudowane są z ujemnie naładowanych łańcuchów polisacharydowych, złożonych z powtarzających się jednostek disacharydowych, do których należą reszty N-acetylowanej heksozoaminy – D-glukozoaminy lub D-galaktozoaminy – albo N-siarczanowanej D-glukozoaminy oraz reszty kwasu heksuronowego – D-glukuronowego lub L-iduronowego – albo galaktozy. Wszystkie GAGs, z wyjątkiem kwasu hialuronowego, posiadają grupę siarczanową oraz tworzą, po przyłączeniu do białek rdzeniowych, proteoglikany (proteoglycans – PGs). GAGs pełnią wiele ważnych biologicznych funkcji, determinujących funkcje PGs. Te ostatnie są obecne we wszystkich rodzajach tkanek, uczestniczą w procesach migracji, proliferacji i różnicowania komórek. Występują głównie w macierzy pozakomórkowej (extracellular matrix – ECM), biorąc udział w organizacji ECM, kształtując jej strukturę i właściwości mechaniczne. Pełnią istotną rolę w utrzymaniu homeostazy, a także wywierają wpływ na szereg procesów metabolicznych, takich jak mineralizacja kości i krzepnięcie krwi. PGs (ze względu na silnie ujemny ładunek łańcuchów glikanowych) biorą udział w selektywnej przepuszczalności błon komórkowych. Składniki ECM, w tym GAGs, odgrywają rolę strukturalno-czynnościową podczas gojenia się uszkodzeń tkankowych. Regulują proces gojenia po-przez stanowienie rezerwuaru i modulatora dla cytokin i czynników wzrostu oraz pełnią funkcje strukturalne poprzez wypełnianie ubytków tkankowych podczas procesu naprawczego.

Keywords

EN

extracellular matrix; glikozoaminoglikany; glycosaminoglycans; gojenie ran; macierz pozakomórkowa; proteoglikany; proteoglycans; wound healing

Discipline

• MEDICINE: MEDICINE

• Publisher: Śląski Uniwersytet Medyczny w Katowicach
• Journal: Annales Academiae Medicae Silesiensis
• Year: 2023
• Issue: 77
• Pages: 204–216

Contributors

author

Kinga Orlińska

• Department of Community Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland

author

Katarzyna Komosińska-Vassev

• Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland

author

Krystyna Olczyk

• Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland

author

Aleksandra Kowalczyk

• Students’ Research Club at the Department of Community Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland

author

Paweł Olczyk

• Department of Community Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland

References

• 1. Biochemia Harpera: ilustrowana. V.W. Rodwell, D.A. Bender, K.M. Botham, P.J. Kennelly, P.A. Weil [eds]. Wyd. Lekarskie PZWL. Warszawa 2018.
• 2. Sufleta A., Mazur-Zielińska H. Glycosaminoglycans – structure, biochemical properties and clinical significance. [Article in Polish]. Ann. Acad. Med. Siles. 2010; 64(5–6): 64–68.
• 3. Daroszewski J., Rybka J., Gamian A. Glycosaminoglycans in the pathogenesis and diagnostics of Graves’s ophthalmopathy. [Article in Polish]. Postepy Hig. Med. Dosw. 2006; 60: 370–378.
• 4. Kroma A., Feliczak-Guzik A., Nowak I. Zastosowanie glikozaminoglikanów w preparatach kosmetycznych. Chemik 2012; 66(2): 136–139.
• 5. Toole B.P., Slomiany M.G. Hyaluronan: a constitutive regulator of chemoresistance and malignancy in cancer cells. Semin. Cancer Biol. 2008; 18(4): 244–250, doi: 10.1016/j.semcancer.2008.03.009.
• 6. Głowacki A., Koźma E.M., Olczyk K., Kucharz E.J. Glikozoamino-glikany – struktura i funkcja. Postepy Biochem. 1995; 41(2): 139–148.
• 7. Sadowski M., Borzyn-Kłuczyk M., Stypułkowska A., Wiełgat P., Zwierz K. Macierz międzykomórkowa ściany żyły. Przegl. Flebol. 2006; 14: 141–149.
• 8. Abaterusso C., Gambaro G. The role of glycosaminoglycans and sulodexide in the treatment of diabetic nephropathy. Treat. Endocrinol. 2006; 5(4): 211–222, doi: 10.2165/00024677-200605040-00002.
• 9. Koźma E.M., Olczyk K., Głowacki A., Bobiński R. An accumulation of proteoglycans in scarred fascia. Mol. Cell. Biochem. 2000; 203(1–2): 103–112, doi: 10.1023/a:1007012321333.
• 10. Im A.R., Kim Y.S. Role of glycosaminoglycans in wound healing. Arch. Pharm. Sci. Res. 2009; 1(2): 106–114 .
• 11. Olczyk P., Mencner Ł., Komosinska-Vassev K. The role of the extracellular matrix components in cutaneous wound healing. Biomed Res. Int. 2014; 2014: 747584, doi: 10.1155/2014/747584.
• 12. Richter R.P., Baranova N.S., Day A.J., Kwok J.C. Glycosaminoglycans in extracellular matrix organisation: are concepts from soft matter physics key to understanding the formation of perineuronal nets? Curr. Opin. Struct. Biol. 2018; 50: 65–74, doi: 10.1016/j.sbi.2017.12.002.
• 13. Głowacki A., Koźma E.M., Olczyk K. Biosynthesis of keratan sulfate, chondroitin sulfate and dermatan sulfate proteoglycans. [Article in Polish]. Postepy Biochem. 2004; 50(2): 170–181.
• 14. Prydz K., Dalen K.T. Synthesis and sorting of proteoglycans. J. Cell Sci. 2000; 113 Pt 2: 193–205, doi: 10.1242/jcs.113.2.193.
• 15. Mizumoto S., Hiroshi Kitagawa H., Sugahara K. Biosynthesis of heparin and heparan sulfate. In: H.G. Garg, R.J. Linhardt, C.A. Hales [eds]. Chemistry and biology of heparin and heparan sulfate. Elsevier. New York 2005, pp. 203––243.
• 16. Toole B.P. Hyaluronan: from extracellular glue to pericellular cue. Nat. Rev. Cancer 2004; 4(7): 528–539, doi: 10.1038/nrc1391.
• 17. Winsz-Szczotka K., Mencner Ł., Olczyk K. Metabolism of glycosemi-noglycans in the course of juvenile idiopathic arthritis. Postepy Hig. Med. Dosw. 2016; 70: 135–142, doi: 10.5604/17322693.1196355.
• 18. Pomin V.H., Vignovich W.P., Gonzales A.V., Vasconcelos A.A., Mulloy B. Galactosaminoglycans: medical applications and drawbacks. Molecules 2019; 24(15): 2803, doi: 10.3390/molecules24152803.
• 19. Zeyland J., Lipiński D., Juzwa W., Pławski A., Słomski R. Structure and application of select glycosaminoglycans. [Article in Polish]. Medycyna Wet. 2006; 62(2): 139–144.
• 20. Mikami T., Kitagawa H. Biosynthesis and function of chondroitin sulfate. Biochim. Biophys. Acta 2013; 1830(10): 4719–4733, doi: 10.1016/j.bbagen.2013.06.006.
• 21. Sasarman F., Maftei C., Campeau P.M., Brunel-Guitton C., Mitchell G.A., Allard P. Biosynthesis of glycosaminoglycans: associated disorders and biochemical tests. J. Inherit. Metab. Dis. 2016; 39(2): 173–188, doi: 10.1007/s10545-015-9903-z.
• 22. Volpi N. Chondroitin sulfate safety and quality. Molecules 2019; 24(8): 1447, doi: 10.3390/molecules24081447.
• 23. Gandhi N.S., Mancera R.L. The structure of glycosaminoglycans and their interactions with proteins. Chem. Biol. Drug Des. 2008; 72(6): 455–482, doi: 10.1111/j.1747-0285.2008.00741.x.
• 24. Carlsson P., Kjellén L. Heparin biosynthesis. In: R. Lever, B. Mulloy, C.P. Page [eds]. Heparin – A century of progress. Springer. Berlin, Heidelberg 2012, pp. 23–41, doi: 10.1007/978-3-642-23056-1_2.
• 25. Wang S., Sugahara K., Li F. Chondroitin sulfate/dermatan sulfate sulfatases from mammals and bacteria. Glycoconj. J. 2016; 33(6): 841–851, doi: 10.1007/s10719-016-9720-0.
• 26. Silbert J.E., Sugumaran G. Biosynthesis of chondroitin/dermatan sulfate. IUBMB Life 2002; 54(4): 177–186, doi: 10.1080/15216540214923.
• 27. Mende M., Bednarek C., Wawryszyn M., Sauter P., Biskup M.B., Schepers U. et al. Chemical synthesis of glycosaminoglycans. Chem. Rev. 2016; 116(14): 8193–8255, doi: 10.1021/acs.chemrev.6b00010.
• 28. Koźma E.M., Głowacki A., Olczyk K., Jaźwiec M. Proteoglycans – structure and functions. [Article in Polish]. Postepy Biochem. 1997; 43(3): 158–172.
• 29. Kaji T., Sakurai S., Yamamoto C., Fujiwara Y., Yamagishi S., Yamamoto H. et al. Characterization of chondroitin/dermatan sulfate proteoglycans synthesized by bovine retinal pericytes in culture. Biol. Pharm. Bull. 2004; 27(11): 1763–1768, doi: 10.1248/bpb.27.1763.
• 30. Han J., Zhang F., Xie J., Linhardt R.J., Hiebert L.M. Changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparin. Cardiovasc. Diabetol. 2009; 8: 46, doi: 10.1186/1475-2840-8-46.
• 31. Malavaki C., Mizumoto S., Karamanos N., Sugahara K. Recent advances in the structural study of functional chondroitin sulfate and dermatan sulfate in health and disease. Connect. Tissue Res. 2008; 49(3): 133–139, doi: 10.1080/03008200802148546.
• 32. Kinsella M.G., Bressler S.L., Wight T.N. The regulated synthesis of versican, decorin, and biglycan: extracellular matrix proteoglycans that influence cellular phenotype. Crit. Rev. Eukaryot. Gene Expr. 2004; 14(3): 203–234, doi: 10.1615/critreveukaryotgeneexpr.v14.i3.40.
• 33. Penc S.F., Pomahac B., Winkler T., Dorschner R.A., Eriksson E., Herndon M. et al. Dermatan sulfate released after injury is a potent promoter of fibroblast growth factor-2 function. J. Biol. Chem. 1998; 273(43): 28116–28121, doi: 10.1074/jbc.273.43.28116.
• 34. Echtermeyer F., Streit M., Wilcox-Adelman S., Saoncella S., Denhez F., Detmar M. et al. Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4. J. Clin. Invest. 2001; 107(2): R9–R14, doi: 10.1172/JCI10559.
• 35. Iozzo R.V., Schaefer L. Proteoglycan form and function: A compre-hensive nomenclature of proteoglycans. Matrix Biol. 2015; 42: 11–55, doi: 10.1016/j.matbio.2015.02.003.
• 36. Farrugia B.L., Lord M.S., Melrose J., Whitelock J.M. The role of heparan sulfate in inflammation, and the development of biomimetics as anti-inflammatory strategies. J. Histochem. Cytochem. 2018; 66(4): 321–336, doi: 10.1369/0022155417740881.
• 37. Sobczak A.I.S., Pitt S.J., Stewart A.J. Glycosaminoglycan neutralization in coagulation control. Arterioscler. Thromb. Vasc. Biol. 2018; 38(6): 1258–1270, doi: 10.1161/ATVBAHA.118.311102.
• 38. Prydz K. Determinants of glycosaminoglycan (GAG) structure. Biomolecules 2015; 5(3): 2003–2022, doi: 10.3390/biom5032003.
• 39. Li L., Ly M., Linhardt R.J. Proteoglycan sequence. Mol. Biosyst. 2012; 8(6): 1613–1625, doi: 10.1039/c2mb25021g.
• 40. Wang W., Wang J., Li F. Hyaluronidase and chondroitinase. In: M.Z. Atassi [ed.]. Protein Reviews. Advances in Experimental Medicine and Biology, vol. 925. Springer. Singapore 2016, pp. 75–87, doi: 10.1007/5584_2016_54.
• 41. Li J.P., Kusche-Gullberg M. Heparan sulfate: biosynthesis, structure, and function. Int. Rev. Cell Mol. Biol. 2016; 325: 215–273, doi: 10.1016/bs.ircmb.2016.02.009.
• 42. Collins L.E., Troeberg L. Heparan sulfate as a regulator of inflammation and immunity. J. Leukoc. Biol. 2019; 105(1): 81–92, doi: 10.1002/JLB.3RU0618-246R.
• 43. Lambers Heerspink H.J., Fowler M.J., Volgi J., Reutens A.T., Klein I., Herskovits T.A. et al. Rationale for and study design of the sulodexide trials in Type 2 diabetic, hypertensive patients with microalbuminuria or overt nephropathy: Short report. Diabet. Med. 2007; 24(11): 1290–1295, doi: 10.1111/j.1464-5491.2007.02249.x.
• 44. Lauver D.A., Lucchesi B.R. Sulodexide: a renewed interest in this glycosaminoglycan. Cardiovasc. Drug Rev. 2006; 24(3–4): 214–226, doi: 10.1111/j.1527-3466.2006.00214.x.
• 45. Rabenstein D.L. Heparin and heparan sulfate: structure and function. Nat. Prod. Rep. 2002; 19(3): 312–331, doi: 10.1039/b100916h.
• 46. Cecora A., Chwała M. Czy glikozaminoglikany zmieniają właściwości ściany żylnej w warunkach zastoju krwi u chorych z przewlekłą niewydolnością żylną? Przeg. Flebolog. 2003; 11: 85–89.
• 47. Ravera M., Re M., Weiss U., Deferrari L., Deferrari G. Emerging therapeutic strategies in diabetic nephropathy. J. Nephrol. 2007; 20 Suppl 12: S23–32.
• 48. Olczyk P., Mencner Ł., Komosinska-Vassev K. Diverse roles of heparan sulfate and heparin in wound repair. Biomed Res. Int. 2015; 2015: 549417, doi: 10.1155/2015/549417.
• 49. Funderburgh J.L. Keratan sulfate biosynthesis. IUBMB Life 2002; 54(4): 187–194, doi: 10.1080/15216540214932.
• 50. Caterson B., Melrose J. Keratan sulfate, a complex glycosaminoglycan with unique functional capability. Glycobiology 2018; 28(4): 182–206, doi: 10.1093/glycob/cwy003.
• 51. Czajkowska D., Milner-Krawczyk M., Kazanecka M. Kwas hialuronowy – charakterystyka, otrzymywanie i zastosowanie. Biotechnol. Food Sci. 2011; 76(2): 55–70, doi: 10.34658/bfs.2011.75.2.55-70.
• 52. Heinegård D. Proteoglycans and more – from molecules to biology. Int. J. Exp. Pathol. 2009; 90(6): 575–586, doi: 10.1111/j.1365-2613.2009.00695.x.
• 53. Rügheimer L. Hyaluronan: a matrix component. AIP Conf. Proc. 2008; 1049: 126–132, doi: 10.1063/1.2998008.
• 54. Kablik J., Monheit G.D., Yu L., Chang G., Gershkovich J. Comparative physical properties of hyaluronic acid dermal fillers. Dermatol. Surg. 2009; 35 Suppl 1: 302–312, doi: 10.1111/j.1524-4725.2008.01046.x.
• 55. Olczyk P., Komosińska-Vassev K., Winsz-Szczotka K., Kuźnik-Trocha K., Olczyk K. Hyaluronan: structure, metabolism, functions, and role in wound healing. [Article in Polish]. Postepy Hig. Med. Dosw. 2008; 62: 651–659.
• 56. Winsz-Szczotka K., Komosińska-Vassev K., Olczyk K. The metabolism of glycosaminoglycans in the course of Graves' disease. Postepy Hig. Med. Dosw. 2006; 60: 184–191.
• 57. Kucia M. Właściwości i zastosowanie kwasu hialuronowego w kosmetologii i medycynie estetycznej. Kosmetol. Estet. 2017; 4(6): 329–335.
• 58. Karamanos N.K., Piperigkou Z., Theocharis A.D., Watanabe H., Franchi M., Baud S. et al. Proteoglycan chemical diversity drives multifunctional cell regulation and therapeutics. Chem. Rev. 2018; 118(18): 9152–9232, doi: 10.1021/acs.chemrev.8b00354.
• 59. Zhu Y., Kruglikov I.L., Akgul Y., Scherer P.E. Hyaluronan in adipo-genesis, adipose tissue physiology and systemic metabolism. Matrix Biol. 2019; 78–79: 284–291, doi: 10.1016/j.matbio.2018.02.012.
• 60. Tammi M.I., Day A.J., Turley E.A. Hyaluronan and homeostasis: a ba-lancing act. J. Biol. Chem. 2002; 277(7): 4581–4584, doi: 10.1074/jbc.R100037200.
• 61. Taylor K.R., Gallo R.L. Glycosaminoglycans and their proteoglycans: host‐associated molecular patterns for initiation and modulation of inflammation. FASEB J. 2006; 20(1): 9–22, doi: 10.1096/fj.05-4682rev.
• 62. Musiał C. Role and application of glycosaminoglycans in trichology and cosmetology. [Article in Polish]. Aesth. Cosmetol. Med. 2021; 10(1): 33–37, doi: 10.52336/acm.2021.10.1.05.
• 63. Kogan G., Soltés L., Stern R., Gemeiner P. Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications. Biotechnol. Lett. 2007; 29(1): 17–25, doi: 10.1007/s10529-006-9219-z.
• 64. Sobczak-Żmuda K., Pasker B., Sosada M. Hyaluronic acid and its derivatives as a component of contemporary pharmaceuticals, cosmetic pro-ducts and dietary supplements. [Article in Polish]. Farm. Pol. 2014; 70(1): 48–54.
• 65. Salwowska N.M., Bebenek K.A., Żądło D.A., Wcisło-Dziadecka D.L. Physiochemical properties and application of hyaluronic acid: a systematic review. J. Cosmet. Dermatol. 2016; 15(4): 520–526, doi: 10.1111/jocd.12237.
• 66. Korzeniowska K., Pawlaczyk M. The hyaluronic acid is not only a cos-metic. Farm. Współcz. 2014; 7: 72–76.
• 67. Morla S. Glycosaminoglycans and glycosaminoglycan mimetics in cancer and inflammation. Int. J. Mol. Sci. 2019; 20(8): 1963, doi: 10.3390/ijms20081963.
• 68. Volpi N., Schiller J., Stern R., Soltés L. Role, metabolism, chemical modifications and applications of hyaluronan. Curr. Med. Chem. 2009; 16(14): 1718–1745, doi: 10.2174/092986709788186138.
• 69. Wan X., Chen Y., Geng F., Sheng Y., Wang F., Guo J. Narrative review of the mechanism of natural products and scar formation in wound repair. Ann. Transl. Med. 2022; 10(4): 236, doi: 10.21037/atm-21-7046.
• 70. desJardins-Park H.E., Foster D.S., Longaker M.T. Fibroblasts and wound healing: an update. Regen. Med. 2018; 13(5): 491–495, doi: 10.2217/rme-2018-0073.
• 71. Zomer H.D., Trentin A.G. Skin wound healing in humans and mice: Challenges in translational research. J. Dermatol. Sci. 2018; 90(1): 3–12, doi: 10.1016/j.jdermsci.2017.12.009.
• 72. de Mendonça R.J., Coutinho-Netto J. Cellular aspects of wound healing. An. Bras. Dermatol. 2009; 84(3): 257–262, doi: 10.1590/s0365-05962009000300007.
• 73. Werner S., Grose R. Regulation of wound healing by growth factors and cytokines. Physiol. Rev. 2003; 83(3): 835–870, doi: 10.1152/physrev.2003.83.3.835.
• 74. Belvedere R., Bizzarro V., Parente L., Petrella F., Petrella A. Effects of Prisma® Skin dermal regeneration device containing glycosaminoglycans on human keratinocytes and fibroblasts. Cell Adh. Migr. 2018; 12(2): 168–183, doi: 10.1080/19336918.2017.1340137.
• 75. Plichta J.K., Radek K.A. Sugar-coating wound repair: a review of FGF-10 and dermatan sulfate in wound healing and their potential application in burn wounds. J. Burn Care Res. 2012; 33(3): 299–310, doi: 10.1097/BCR.0b013e318240540a.
• 76. Olczyk P., Komosinska-Vassev K., Winsz-Szczotka K., Stojko J., Klimek K., Kozma E.M. Propolis induces chondroitin/dermatan sulphate and hyaluronic acid accumulation in the skin of burned wound. Evid. Based Complement. Alternat. Med. 2013; 2013: 290675, doi: 10.1155/2013/290675.
• 77. Deakin J.A., Blaum B.S., Gallagher J.T., Uhrín D., Lyon M. The binding properties of minimal oligosaccharides reveal a common heparan sulfate/dermatan sulfate-binding site in hepatocyte growth factor/scatter factor that can accommodate a wide variety of sulfation patterns. J. Biol. Chem. 2009; 284(10): 6311–6321, doi: 10.1074/jbc.M807671200.
• 78. Bentley J.P. Rate of chondroitin sulfate formation in wound healing. Ann. Surg. 1967; 165(2): 186–191, doi: 10.1097/00000658-196702000-00004.
• 79. Siméon A., Wegrowski Y., Bontemps Y., Maquart F.X. Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide–copper complex glycyl-L-histidyl-L-lysine-Cu2+. J. Invest. Dermatol. 2000; 115(6): 962–968, doi: 10.1046/j.1523-1747.2000.00166.x.
• 80. Ghatak S., Maytin E.V., Mack J.A., Hascall V.C., Atanelishvili I., Moreno Rodriguez R. et al. Roles of proteoglycans and glycosaminoglycans in wound healing and fibrosis. Int. J. Cell Biol. 2015; 2015: 834893, doi: 10.1155/2015/834893.
• 81. Olczyk P., Komosińska-Vassev K., Winsz-Szczotka K., Koźma E.M., Wisowski G., Stojko J. et al. Propolis modulates vitronectin, laminin, and heparan sulfate/heparin expression during experimental burn healing. J. Zhejiang Univ. Sci. B 2012; 13(11): 932–941, doi: 10.1631/jzus.B1100310.
• 82. Tong M., Zbinden M.M., Hekking I.J.M., Vermeij M., Barritault D., van Neck J.W. RGTA OTR 4120, a heparan sulfate proteoglycan mimetic, increases wound breaking strength and vasodilatory capability in healing rat full-thickness excisional wounds. Wound Repair Regen. 2008; 16(2): 294–299, doi: 10.1111/j.1524-475X.2008.00368.x.
• 83. Xu D., Esko J.D. Demystifying heparan sulfate-protein interactions. Annu. Rev. Biochem. 2014; 83: 129–157, doi: 10.1146/annurev-biochem-060713-035314.
• 84. Oksala O., Salo T., Tammi R., Häkkinen L., Jalkanen M., Inki P. et al. Expression of proteoglycans and hyaluronan during wound healing. J. Histochem. Cytochem. 1995; 43(2): 125–135, doi: 10.1177/43.2.7529785.
• 85. Frenkel J.S. The role of hyaluronan in wound healing. Int. Wound J. 2014; 11(2): 159–163, doi: 10.1111/j.1742-481X.2012.01057.x.
• 86. Weigel P.H., Frost S.J., LeBoeuf R.D., McGary C.T. The specific interaction between fibrin(ogen) and hyaluronan: possible consequences in haemostasis, inflammation and wound healing. Ciba Found. Symp. 1989; 143: 248–261, doi: 10.1002/9780470513774.ch15.
• 87. Averbeck M., Gebhardt C.A., Voigt S., Beilharz S., Anderegg U., Termeer C.C. et al. Differential regulation of hyaluronan metabolism in the epidermal and dermal compartments of human skin by UVB irradiation. J. Invest. Dermatol. 2007; 127(3): 687–697, doi: 10.1038/sj.jid.5700614.
• 88. Hamed S., Bennett C.L., Demiot C., Ullmann Y., Teot L., Desmoulière A. Erythropoietin, a novel repurposed drug: an innovative treatment for wound healing in patients with diabetes mellitus. Wound Repair Regen. 2014; 22(1): 23–33, doi: 10.1111/wrr.12135.
• 89. Hamed S., Ullmann Y., Egozi D., Keren A., Daod E., Anis O. et al. Topical erythropoietin treatment accelerates the healing of cutaneous burn wounds in diabetic pigs through an aquaporin-3-dependent mechanism. Diabetes 2017; 66(8): 2254–2265, doi: 10.2337/db16-1205.
• 90. Olczyk P., Wisowski G., Komosinska-Vassev K., Stojko J., Klimek K., Olczyk M. et al. Propolis modifies collagen types I and III accumulation in the matrix of burnt tissue. Evid. Based Complement. Alternat. Med. 2013; 2013: 423809, doi: 10.1155/2013/423809.
• 91. Olczyk P., Komosinska-Vassev K., Wisowski G., Mencner L., Stojko J., Kozma E.M. Propolis modulates fibronectin expression in the matrix of thermal injury. Biomed Res. Int. 2014; 2014: 748101, doi: 10.1155/2014/748101.
• 92. Hoekstra M.J., Hupkens P., Dutrieux R.P., Bosch M.M., Brans T.A., Kreis R.W. A comparative burn wound model in the New Yorkshire pig for the histopathological evaluation of local therapeutic regimens: silver sulfadiazine cream as a standard. Br. J. Plast. Surg. 1993; 46(7): 585–589, doi: 10.1016/0007-1226(93)90111-N.

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