American Journal of Clinical Dermatology

, Volume 6, Issue 6, pp 393–402 | Cite as

The Role of Hyaluronic Acid in Wound Healing

Assessment of Clinical Evidence
  • Richard D. Price
  • Simon Myers
  • Irene M. Leigh
  • Harshad A. NavsariaEmail author
Review Article


Hyaluronic acid (hyaluronan), a naturally occurring polymer within the skin, has been extensively studied since its discovery in 1934. It has been used in a wide range of medical fields as diverse as orthopedics and cosmetic surgery, but it is in tissue engineering that it has been primarily advanced for treatment. The breakdown products of this large macromolecule have a range of properties that lend it specifically to this setting and also to the field of wound healing. It is non-antigenic and may be manufactured in a number of forms, ranging from gels to sheets of solid material through to lightly woven meshes. Epidermal engraftment is superior to most of the available biotechnologies and, as such, the material shows great promise in both animal and clinical studies of tissue engineering. Ongoing work centers around the ability of the molecule to enhance angiogenesis and the conversion of chronic wounds into acute wounds.


Tissue Engineering Hyaluronic Acid Chronic Wound Pyoderma Gangrenosum Epidermolysis Bullosa 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Thank you to Fidia Advanced Biopolymers, Italy for figures 2, 3 and 4. Part of this work was supported by the BRITE-Euram grant BE3524. The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Rheinwald JG, Green H. Formation of a keratinizing epithelium in culture by a cloned cell line derived from a teratoma. Cell 1975; 6 (3): 317–30PubMedCrossRefGoogle Scholar
  2. 2.
    Bell E, Ivarsson B, Merrill C. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci U S A. 1979; 76 (3): 1274–8PubMedCrossRefGoogle Scholar
  3. 3.
    Martin P. Wound healing: aiming for perfect skin regeneration. Science. 1997; 276: 75–81PubMedCrossRefGoogle Scholar
  4. 4.
    Pavesio A, Abatangelo G, Borrione A, et al. Hyaluronan-based scaffolds (HyaLograft C) in the treatment of knee cartilage defects: preliminary clinical findings. Novartis Found Symp 2003; 249: 203–17PubMedCrossRefGoogle Scholar
  5. 5.
    Friedman JA, Windebank AJ, Moore MJ, et al. Biodegradable polymer grafts for surgical repair of the injured spinal cord. Neurosurgery 2002; 51 (3): 751–2Google Scholar
  6. 6.
    Doolin EJ, Strande LF, Sheng X, et al. Engineering a composite trachea with surgical adhesives. J Paediatr Surg 2002; 37 (7): 1034–7CrossRefGoogle Scholar
  7. 7.
    Shah M, Foreman DM, Ferguson MW. Neutralisation of TGF-ß 1 and TGF-ß 2 or exogenous addition of TGF-ß 3 to cutaneous rat wounds reduces scarring. J Cell Sci. 1995; 108 (Pt 3): 985–1002PubMedGoogle Scholar
  8. 8.
    O’Kane S, Ferguson MW. Transforming growth factor Bs and wound healing. Int J Biochem Cell Biol. 1997; 29 (1): 63–78PubMedCrossRefGoogle Scholar
  9. 9.
    Yannas IV, Lee E, Orgill DP, et al. Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin. Proc Nall Acad Sci U S A. 1989; 86 (3): 933–7CrossRefGoogle Scholar
  10. 10.
    Harris PA, di Francesco F, Barisoni D, et al. Use of hyaluronic acid and cultured autologous keratinocytes and fibroblasts in extensive burns [letter]. Lancet. 1999; 353 (9146): 35–6PubMedCrossRefGoogle Scholar
  11. 11.
    Aigner J, Tegeler J, Hutzler P, et al. Cartilage tissue engineering with novel nonwoven structured biomaterial based on hyaluronic acid benzyl ester. J Biomed Mater Res. 1998; 42 (2): 172–81PubMedCrossRefGoogle Scholar
  12. 12.
    Maleski M, Hockfield S. Glial cells assemble hyaluronan-based pericellular matrices in vitro. Glia. 1997; 20 (3): 193–202PubMedCrossRefGoogle Scholar
  13. 13.
    Neuwinger J, Cooper TG, Knuth UA, et al. Hyaluronic acid as a medium for human sperm migration tests. Hum Reprod. 1991; 6 (3): 396–400PubMedGoogle Scholar
  14. 14.
    Wiegel PH, Frost SJ, LeBoeuf RD, McGary CT. The specific interaction between fibrin (ogen) and hyaluronan: possible consequences in haemostasis, inflammation and wound healing. In: Evered D, Whelan J, editors. The biology of hyaluronan (Ciba Foundation Symposium 143). Chichester: Wiley, 1989: 248–6Google Scholar
  15. 15.
    Schiller S. Synthesis of hyaluronic acid by a soluble enzyme system from mammalian tissue. Biochem Biophys Res Commun. 1964; 15 (3): 250–5PubMedCrossRefGoogle Scholar
  16. 16.
    Campoccia D, Doherty P, Radice M, et al. Review: semisynthetic resorbable materials from hyaluronan esterification. Biomaterials. 1998; 19: 2101–27PubMedCrossRefGoogle Scholar
  17. 17.
    Lesley J, Hyman R, Kincade PW. CD44 and its interaction with extracellular matrix. Adv Immunol. 1993; 54: 271–335PubMedCrossRefGoogle Scholar
  18. 18.
    Brown MR, Foster IH, Clamp JR. Composition of Pseudomonas aeruginosa slime. Biochem 1. 1969; 112 (4): 521–5Google Scholar
  19. 19.
    Rahemtulla F, Lovtrup S. The comparative biochemistry of invertebrate mucopolysaccharides II. Nematoda; Annelida. Comp Biochem Physiol. 1974; 49 (4): 639–46Google Scholar
  20. 20.
    Yamada K. Effects of novel (Streptomyces) hyaluronidase digestion upon some mucosaccharide stainings of the cartilages and aortas in the rabbit and rat. Histochemie. 1971; 27 (4): 277–89PubMedCrossRefGoogle Scholar
  21. 21.
    Fleischmajer R, Perlish IS, Gaisin A. Comparative study of dermal glycosaminoglycans. J Invest Dermatol. 1973; 61 (1): 1–6PubMedCrossRefGoogle Scholar
  22. 22.
    Singh M, Chandrasekaran EV, Cherian R, et al. Isolation and characterization of glycosaminoglycans in brain of different species. J Neurochem. 1969; 16 (7): 1157–62PubMedCrossRefGoogle Scholar
  23. 23.
    Kobayashi Y, Okamoto A, Nishinari K. Viscoelasticity of hyaluronic acid with different molecular weights. Biorheology. 1994; 31 (3): 235–44PubMedGoogle Scholar
  24. 24.
    Laurent TC, Fraser J. Hyaluronan. FASEB 1992; 6 (7): 2397–404Google Scholar
  25. 25.
    Barbucci R, Magnani A, Baszkin A, et al. Physico-chemical surface characterisation of hyalmonic acid derivatives as a new class of biomaterials. J Biomat Sci Poly Ed. 1993; 4 (3): 245–73CrossRefGoogle Scholar
  26. 26.
    Manna F, Dentini M, Desideri P, et al. Comparative chemical evaluation of two commercially available derivatives of hyaluronic acid (hyalaform (R) from rooster combs and restylane (R) from Streptococcus) used for soft tissue augmentation. J Fur Acad Dermatol Venereol. 1999; 13 (3): 183–92Google Scholar
  27. 27.
    Weigel PH, Hascall VC, Tammi M. Hyaluronan synthases. J Biol Chem. 1997; 272 (22): 13997–4000PubMedCrossRefGoogle Scholar
  28. 28.
    Stern R, McPherson M, Longaker MT. Histologic study of artificial skin used in the treatment of full-thickness thermal injury. J Burn Care Rehabil 1990; 11 (1): 7–13PubMedCrossRefGoogle Scholar
  29. 29.
    Aruffo A, Stamenkovic I, Melnick M, et al. CD44 is the principal cell surface receptor for hyalmonate. Cell. 1990; 61 (7): 1303–13PubMedCrossRefGoogle Scholar
  30. 30.
    Bajorath J, Greenfield B, Munro SB, et al. Identification of CD44 residues important for hyaluronan binding and delineation of the binding site. J Biol Chem. 1998; 273 (1): 338–43PubMedCrossRefGoogle Scholar
  31. 31.
    Bartolazzi A, Peach R, Aruffo A, et al. Interaction between CD44 and hyalmonate is directly implicated in the regulation of tumor development. J Exp Med. 1994; 180 (1): 53–66PubMedCrossRefGoogle Scholar
  32. 32.
    Teder P, Bergh J, Heldin P. Functional hyaluronan receptors are expressed on a squamous cell lung carcinoma cell line but not on other lung carcinoma cell lines. Cancer Res. 1995; 55 (17): 3908–14PubMedGoogle Scholar
  33. 33.
    Bartolami CN, Berg S, Messadi DV. Binding and internalisation ofhyaluronate by human cutaneous fibroblasts. Matrix. 1992; 11: 11–21CrossRefGoogle Scholar
  34. 34.
    West DC, Hampson IN, Arnold F, et al. Angiogenesis induced by degradation products of hyaluronic acid. Science. 1991; 228: 1324–6CrossRefGoogle Scholar
  35. 35.
    Sattar A, Rooney P, Kumar S, et al. Application of angiogenic oligosaccharides of hyaluronan increases blood vessel numbers in rat skin. J Invest Dermatol. 1994; 103: 576–9PubMedCrossRefGoogle Scholar
  36. 36.
    Trochon V, Mabilat-Pragnon C, Bertrand P, et al. Hyaluronectin blocks the stimulatory effect of hyaluronan-derived fragments on endothelial cells during angiogenesis in vitro. FEBS Lett. 1997; 418 (1-2): 6–10PubMedCrossRefGoogle Scholar
  37. 37.
    Deed R, Rooney P, Kumar P, et al. Early-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan. Int J Cancer. 1997; 71 (2): 251–6PubMedCrossRefGoogle Scholar
  38. 38.
    Slevin M, Krupinski J, Kumar S, et al. Angiogenic oligosaccharides of hyaluronan induce protein tyrosine kinase activity in endothelial cells and activate a cytoplasmic signal transduction pathway resulting in proliferation. Lab Invest. 1998; 78 (8): 987–1003PubMedGoogle Scholar
  39. 39.
    Slevin M, Kumar S, Gaffney J. Angiogenic oligosaccharides of hyaluronan induce multiple signaling pathways affecting vascular endothelial cell mitogenic and wound healing responses. J Biol Chem 2002; 277 (43): 41046–59PubMedCrossRefGoogle Scholar
  40. 40.
    Montesano R, Kumar S, Orci L, et al. Synergistic effect of hyaluronan oligosaccharides and vascular endothelial growth factor on angiogenesis in vitro. Lab Invest. 1996; 75 (2): 249–62PubMedGoogle Scholar
  41. 41.
    Franzmann EJ, Schroeder GL, Goodwin WJ, et al. Expression of tumor markers hyaluronic acid and hyaluronidase (HYALI) in head and neck tumors. Int J Cancer 2003; 106 (3): 438–45PubMedCrossRefGoogle Scholar
  42. 42.
    Zimmerman E, Geiger B, Addadi L. Initial stages of cell-matrix adhesion can be mediated and modulated by cell-surface hyaluronan. Biophys J 2002; 82 (4): 1848–57PubMedCrossRefGoogle Scholar
  43. 43.
    Turley EA, Austen L, Vandeligt K, et al. Hyaluronan and a cell-associated hyaluronan binding protein regulate the locomotion of ras-transformed cells. J Cell Biol. 1991; 112: 1041–7PubMedCrossRefGoogle Scholar
  44. 44.
    Mesa FL, Aneiros J, Cabrera A, et al. Antiproliferative effect of topic hyaluronic acid gel: study in gingival biopsies of patients with periodontal disease. Histol Histopathol 2002; 17: 747–53PubMedGoogle Scholar
  45. 45.
    Greco RM, Iocono JA, Ehrlich HP. Hyaluronic acid stimulates human fibroblast proliferation within a collagen matrix. J Cell Physiol. 1998; 177: 465–73PubMedCrossRefGoogle Scholar
  46. 46.
    Mast BA, Diegelmann RF, Krummel TM, et al. Hyaluronic acid modulates proliferation, collagen and protein synthesis of cultured fetal fibroblasts. Matrix. 1993; 13 (6): 441–6PubMedCrossRefGoogle Scholar
  47. 47.
    Ikeda K, Yamauchi D, Osamura N, et al. Hyalmonic acid prevents peripheral nerve adhesion. Br J Plast Surg. 2003; 56 (4): 342–7PubMedCrossRefGoogle Scholar
  48. 48.
    Songer MN, Ghosh L, Spencer DL. Effects of sodium hyaluronate on peridural fibrosis after lumbar laminotomy and discectomy. Spine. 1990; 15 (6): 550–4PubMedCrossRefGoogle Scholar
  49. 49.
    Croce MA, Dyne K, Boraldi F, et al. Hyaluronan affects protein and collagen synthesis by in vitro human skin fibroblasts. Tissue Cell. 2001; 33 (4): 326–31PubMedCrossRefGoogle Scholar
  50. 50.
    Iocono JA, Krummel TM, Keefer KA, et al. Repeated additions of hyaluronan alters granulation tissue deposition in sponge implants in mice. Wound Repair Regen. 1998; 6): 442–8PubMedCrossRefGoogle Scholar
  51. 51.
    Kielty CM, Whittaker SP, Grant ME, et al. Type IV collagen microfibrils: evidence for a structural association with hyaluronan. J Cell Biol. 1992; 118 (4): 979–90PubMedCrossRefGoogle Scholar
  52. 52.
    Rooney P, Kumar S. Inverse relationship between hyaluronan and collagens in development and angiogenesis. Differentiation. 1993; 54: 1–9PubMedGoogle Scholar
  53. 53.
    Scully MF, Kakkar VJ, Goodwin CA, et al. Inhibition of fibrinolytic activity by hyaluronan and its alcohol ester derivatives. Thromb Res. 1995; 78 (3): 255–8PubMedCrossRefGoogle Scholar
  54. 54.
    Alaish SM, Yager DR, Diegelmann RF, et al. Hyaluronic acid metabolism in keloid fibroblasts. J Pediatr Surg. 1995; 30 (7): 949–52PubMedCrossRefGoogle Scholar
  55. 55.
    Germain L, Jean A, Auger FA, et al. Human wound healing fibroblasts have greater contractile properties than dermal fibroblasts. J Surg Res. 1994; 57 (2): 268–73PubMedCrossRefGoogle Scholar
  56. 56.
    Travis JA, Hughes MG, Wong JM, et al. Hyaluronan enhances contraction of collagen by smooth muscle cells and adventitial fibroblasts: role of CD44 and implications for constrictive remodeling. Cite Res. 2001; 88 (1): 77–83CrossRefGoogle Scholar
  57. 57.
    Heldin P, Laurent TC, Heldin CH. Effect of growth factors on hyaluronan synthesis in cultured human fibroblasts. Biochem J. 1989; 258 (3): 919–22PubMedGoogle Scholar
  58. 58.
    Longaker MT, Chin ES, Adzick NS, et al. Studies in fetal wound healing: V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid. Ann Surg. 1991; 213 (4): 292–6PubMedCrossRefGoogle Scholar
  59. 59.
    Sawai T, Usui N, Sando K, et al. Hyaluronic acid of wound fluid in adult and fetal rabbits. J Pediatr Surg. 1997; 32 (1): 41–3PubMedCrossRefGoogle Scholar
  60. 60.
    West DC, Shaw DM, Lorenz P, et al. Fibrotic healing of adult and late gestation fetal wounds correlates with increased hyaluronidase activity and removal of hyaluronan. Int J Biochem Cell Biol. 1997; 29 (1): 201–10PubMedCrossRefGoogle Scholar
  61. 61.
    Humng-Lee LL, Nimni ME. Fibroblast contraction of collagen matrices with and without covalently bound hyaluronan. J Biomater Sci Polym Ed. 1993; 5 (1-2): 99–109CrossRefGoogle Scholar
  62. 62.
    Ellis I, Banyard J, Schor SL. Differential response of fetal and adult fibroblasts to cytokines: cell migration and hyaluronan synthesis. Development. 1997; 124 (8): 1593–600PubMedGoogle Scholar
  63. 63.
    Iocono JA, Ehrlich HP, Keefer KA, et al. Hyaluronan induces scarless repair in mouse limb organ culture. J Pediatr Surg. 1998; 33 (4): 564–7PubMedCrossRefGoogle Scholar
  64. 64.
    Lovvorn HN, Cass DL, Sylvester KG, et al. Hyaluronan receptor expression increases in fetal excisional skin wounds and correlates with fibroplasia. J Pediatr Surg. 1998; 33 (7): 1062–9PubMedCrossRefGoogle Scholar
  65. 65.
    Meyer LJ, Stern R. Age-dependent changes of hyaluronan in human skin. J Invest Dermatol. 1994; 102 (3): 385–9PubMedCrossRefGoogle Scholar
  66. 66.
    Hellkvist J, Tufveson G, Gerdin B, et al. Characterization of fibroblasts from rejecting tissue: the hyaluronan production is increased. Transplantation. 2002; 74 (12): 1672–7PubMedCrossRefGoogle Scholar
  67. 67.
    Cabrera RC, Siebert JW, Eidelman Y, et al. The in vivo effect of hyaluronan associated protein-collagen complex in wound repair. Biochem Mot Biol Int. 1995; 37: 151–8Google Scholar
  68. 68.
    Tammi R, MacCallum D, Hascall VC, et al. Hyalmonan bound to CD44 on keratinocytes is displaced by hyaluronan decasaccharides and not hexasaccharides. J Biel Chem. 1998; 273 (44): 28878–88CrossRefGoogle Scholar
  69. 69.
    Pienimaki JP, Rilla K, Fulop C, et al. Epidermal growth factor activates hyaluronan synthase 2 in epidermal keratinocytes and increases pericellular and intracellular hyaluronan. J Biol Chem. 2001; 276: 20428–35PubMedCrossRefGoogle Scholar
  70. 70.
    Zhou J, Haggerty JG, Milstone LM. Growth and differentiation regulate CD44 expression on human keratinocytes. In Vitro Cell Dev Biol Anim. 1999; 35: 228–35PubMedCrossRefGoogle Scholar
  71. 71.
    Tammi R, Tammi M. Correlations between hyaluronan and epidermal proliferation as studied by3H-glucosamine and 3H-thymidine incorporations and staining of hyaluronan on mitotic keratinocytes. Exp Cell Res. 1991; 195: 524–7PubMedCrossRefGoogle Scholar
  72. 72.
    Tammi R, Rilla K, Pienimaki JP, et al. Hyalmonan enters keratinocytes by a novel endocytic route for catabolism. J Biel Chem. 2001; 276 (37): 35111–22CrossRefGoogle Scholar
  73. 73.
    Inoue M, Katakami C. The effect of hyalmonic acid on corneal epithelial cell proliferation. Invest Ophthalmol Vis Sci. 1993; 34: 2313–5PubMedGoogle Scholar
  74. 74.
    Nishida T, Nakamura M, Mishima H, et al. Hyaluronan stimulates corneal epithelial migration. Exp Eye Res. 1991; 53 (6): 753–8PubMedCrossRefGoogle Scholar
  75. 75.
    Pasonen-Seppanen S, Karvinen S, Torronen K, et al. EGF upregulates, whereas TGF-ß downregulates, the hyaluronan synthases Has2 and Has3 in organotypic keratinocyte cultures: correlations with epidermal proliferation and differentiation. J Invest Dermatol. 2003; 120 (6): 1038–44PubMedCrossRefGoogle Scholar
  76. 76.
    Pienimaki JP, Rilla K, Fulop C, et al. Epidermal growth factor activates hyaluronan synthase 2 in epidermal keratinocytes and increases pericellular and intracellular hyaluronan. J Biol Chem. 2001; 276 (23): 20428–35PubMedCrossRefGoogle Scholar
  77. 77.
    Castor CW, Greene JA. Regional distribution of acid mucopolysaccharides in the kidney. J Clin Invest. 1968; 47 (9): 2125–32PubMedCrossRefGoogle Scholar
  78. 78.
    Sisson JC. Hyaluronic acid in localized myxedema. J Clin Endocrinol Metab. 1968; 28 (4): 433–6PubMedCrossRefGoogle Scholar
  79. 79.
    Hodson JJ, Prout RE. Chemical and histechemical characterization of mucopolysaccharides in a jaw myxoma. J Clin Pathol. 1968; 21 (5): 582–9PubMedCrossRefGoogle Scholar
  80. 80.
    Fatini G, Gallenga G, Veltroni A. Treatment of burns with hyaluronic acid: clinical study [in Italian]. Osp Ital Chir. 1968; 19 (3): 283–7PubMedGoogle Scholar
  81. 81.
    Bertelli G, Dim D, Forno GB, et al. Hyaluronidase as an antidote to extravasation of Vinca alkaloids: clinical results. J Cancer Res Clin Oncol. 1994; 120: 505–6PubMedCrossRefGoogle Scholar
  82. 82.
    Edelstam GA, Lundkvist O, Venge P, et al. Hyaluronan and myeloperoxidase in human peritoneal fluid during genital inflammation. Inflammation. 1994; 18: 13–21PubMedCrossRefGoogle Scholar
  83. 83.
    Rheinwald JG, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975; 6 (3): 331–43PubMedCrossRefGoogle Scholar
  84. 84.
    Cuono CB, Langdon R, Birchall S, et al. Composite autologous-allogenic skin replacement: development and clinical application. Plast Reconstr Surg. 1987; 80: 626–35PubMedCrossRefGoogle Scholar
  85. 85.
    Kangesu T, Navsaria HA, Manek S, et al. Kerato-dermal grafts: the importance of dermis for the in vivo growth of cultured keratinocytes. Br J Plast Surg. 1993; 46 (5): 401–9PubMedCrossRefGoogle Scholar
  86. 86.
    Wallace AF. The progress of plastic surgery. 1st ed. Oxford: Willem A. Meeuws, 1982: 184Google Scholar
  87. 87.
    Yannas IV. Studies on the biological activity of the dermal regeneration template. Wound Repair Regen. 1998; 6 (6): 518–23PubMedCrossRefGoogle Scholar
  88. 88.
    Myers SR, Grady J, Soranzo C, et al. A hyaluronic acid membrane delivery system for cultured keratinocytes: clinical take rates in the porcine kerate-dermal model. J Burn Care Rehabil. 1997; 18 (3): 214–22PubMedCrossRefGoogle Scholar
  89. 89.
    Lam PK, Chan ES, To EW, et al. Development and evaluation of a new composite Laserskin graft. J Trauma. 1999; 47 (5): 918–22PubMedCrossRefGoogle Scholar
  90. 90.
    Harris PA, Leigh IM, Navsaria HA. Pre-confluent keratinocyte grafting: the future for cultured skin replacements?. Burns. 1998; 24 (7): 591–3PubMedCrossRefGoogle Scholar
  91. 91.
    Hollander D, Stein M, Bernd A, et al. Autologous keratinocytes cultured on benzylester hyaluronic acid membranes in the treatment of chronic full-thickness ulcers. J Wound Care. 1999; 8 (7): 351–5PubMedGoogle Scholar
  92. 92.
    Lohmann R, Pittasch D, Muhlen I, et al. Autologous human keratinocytes cultured on membranes composed of benzyl ester of hyaluronic acid for grafting in nonhealing diabetic foot lesions: a pilot study. J Diabetes Complications. 2003; 17 (4): 199–204CrossRefGoogle Scholar
  93. 93.
    Bruce SA, Deamond SF. Longitudinal study of in vivo wound repair and in vitro cellular senescence of dermal fibroblasts. Exp Gerontol. 1991; 26 (1): 17–27PubMedCrossRefGoogle Scholar
  94. 94.
    Regan MC, Kirk SJ, Wasserkrug HL, et al. The wound environment as a regulator of fibroblast phenotype. J Surg Res. 1991; 50 (5): 442–8PubMedCrossRefGoogle Scholar
  95. 95.
    van de Berg IS, Rudolph R, Hollan C, et al. Fibroblast senescence in pressure ulcers. Wound Repair Regen. 1998; 6 (1): 38–49CrossRefGoogle Scholar
  96. 96.
    Hehenberger K, Heilborn JD, Brismar K, et al. Inhibited proliferation of fibroblasts derived from chronic diabetic wounds and normal dermal fibroblasts treated with high glucose is associated with increased formation of 1-lactate. Wound Repair Regen. 1998; 6 (2): 135–41PubMedCrossRefGoogle Scholar
  97. 97.
    He C, Hughes MA, Cherry GW, et al. Effects of chronic wound fluid on the bioactivity of platelet-derived growth factor in serum-free medium and its direct effect on fibroblast growth. Wound Repair Regen. 1999; 7 (2): 97–105PubMedCrossRefGoogle Scholar
  98. 98.
    Hasan A, Murata H, Falabella A, et al. Dermal fibroblasts from venous ulcers are unresponsive to the action of transforming growth factor-ß 1. J Dermatol Sci. 1997; 16 (1): 59–66PubMedCrossRefGoogle Scholar
  99. 99.
    Stanley AC, Park HY, Phillips TJ, et al. Reduced growth of dermal fibroblasts from chronic venous ulcers can be stimulated with growth factors. J Vase Surg. 1997; 26 (6): 994–9CrossRefGoogle Scholar
  100. 100.
    Eaglstein WH, Falanga V. Tissue engineering and the development of Apligraf, a human skin equivalent. Clin Ther. 1997; 19 (5): 894–905PubMedCrossRefGoogle Scholar
  101. 101.
    Falanga V. Occlusive wound dressings. Arch Dermatol. 1988; 124: 872–7PubMedCrossRefGoogle Scholar
  102. 102.
    Trent IF, Kirsner RS. Tissue engineered skin: Apligraf, a bilayered living skin equivalent. Int J Clin Pract. 1998; 52 (6): 408–13PubMedGoogle Scholar
  103. 103.
    Brain A, Purkis P, Coates P, et al. Survival of cultured allogeneic keratinocytes transplanted to deep dermal bed assessed with probe specific for Y chromosome. BMJ. 1989; 298 (6678): 917–9PubMedCrossRefGoogle Scholar
  104. 104.
    McGrath JA, Leigh IM, Eady RA. Intracellular expression of type VII collagen during wound healing in severe recessive dystrophic epidermolysis bullosa and normal human skin. Br J Dermatol. 1992; 127 (4): 312–7PubMedCrossRefGoogle Scholar
  105. 105.
    Morley SM, Dundas SR, James JL, et al. Temperature sensitivity of the keratin cyteskeleten and delayed spreading of keratinocyte lines derived from EBS patients. J Cell Sci. 1995; 108 (Pt 11): 3463–71PubMedGoogle Scholar
  106. 106.
    D’Alessandro M, Russell D, Morley SM, et al. Keratin mutations of epidermolysis bullosa simplex alter the kinetics of stress response to osmotic shock. J Cell Sci. 2002; 115 (Pt 22): 4341–51PubMedCrossRefGoogle Scholar
  107. 107.
    McGrath JA, Schofield OM, Ishida-Yamamoto A, et al. Cultured keratinocyte allografts and wound healing in severe recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 1993; 29 (3): 407–19PubMedCrossRefGoogle Scholar
  108. 108.
    Wollina U, Konrad H, Fischer T. Recessive epidermolysis bullosa dystrophicans (Hallopeau-Siemens): improvement of wound healing by autologous epidermal grafts on an esterified hyaluronic acid membrane. J Dermatol 2001; 28: 217–20PubMedGoogle Scholar
  109. 109.
    Bell E, Ehrlich HP, Sher S, et al. Development and use of a living skin equivalent. Plast Reconstr Surg. 1981; 67 (3): 386–92PubMedCrossRefGoogle Scholar
  110. 110.
    Price RD, Hodgkins V, Harris PA, et al. Do allogenic fibroblasts survive transplantation? [abstract]. Wound Repair Regen and Aug. 1999; 7 (4): A314.Google Scholar
  111. 111.
    Chan ES, Lam PK, Liew CT, et al. A new technique to resurface wounds with composite biocompatible epidermal graft and artificial skin. J Trauma. 2001; 50 (2): 358–62PubMedCrossRefGoogle Scholar
  112. 112.
    Campoccia D, Hunt JA, Doherty PJ, et al. Quantitative assessment of the tissue response to films of hyaluronan esters. Biomaterials. 1996; 17: 963–75PubMedCrossRefGoogle Scholar
  113. 113.
    Price RD, Das-Gupta V, Frame JD, et al. A study to evaluate primary dressings for the application of cultured keratinocytes. Br J Plast Surg. 2001; 54 (8): 687–96PubMedCrossRefGoogle Scholar
  114. 114.
    Kirker KR, Luo Y, Nielson JH, et al. Glycosaminoglycan hydrogel films as biointeractive dressings for wound healing. Biomaterials. 2002; 23: 3661–71PubMedCrossRefGoogle Scholar
  115. 115.
    Hollander DA, Soranzo C, Falk S, et al. Extensive traumatic soft tissue loss: reconstruction in severely injured patients using cultured hyaluronan-based three-dimensional dermal and epidermal autografts. J Trauma. 2001; 50 (6): 1125–36PubMedCrossRefGoogle Scholar
  116. 116.
    Vazquez JR, Short B, Findlow AH et al. Outcomes of hyaluronan therapy in diabetic foot wounds. Diabetes Res Clin Pract. 2003; 59 (2): 123–7PubMedCrossRefGoogle Scholar
  117. 117.
    Martini A, Morm B, Aimoni C, et al. Use of a hyaluronan-based biomembrane in the treatment of chronic cholesteatomatous otitis media. Am J Otol. 2000; 21 (4): 468–73PubMedGoogle Scholar
  118. 118.
    Landeen LK, Zeigler FC, Halberstadt C, et al. Characterisation of a human dermal replacement. Wounds. 1992; 5: 167–75Google Scholar
  119. 119.
    Galassi G, Brun P, Radice M, et al. In vitro reconstructed dermis implanted in human wounds: degradation studies of the HA-based supporting scaffold. Biomaterials. 2000; 21 (21): 2183–91PubMedCrossRefGoogle Scholar
  120. 120.
    Tonello C, Zavan B, Cortivo R, et al. In vitro reconstruction of human dermal equivalent enriched with endothelial cells. Biomaterials. 2003; 24 (7): 1205–11PubMedCrossRefGoogle Scholar
  121. 121.
    Lees VC, Fan TP, West DC. Angiogenesis in a delayed revascularization model is accelerated by angiogenic oligosaccharides of hyalmonan. Lab Invest. 1995; 73 (2): 259–66PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Richard D. Price
    • 1
    • 2
  • Simon Myers
    • 2
  • Irene M. Leigh
    • 2
  • Harshad A. Navsaria
    • 2
    Email author
  1. 1.South Manchester University Hospitals NHS TrustManchesterUK
  2. 2.Centre for Cutaneous Research, Queen Mary CollegeUniversity of LondonLondonUK

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