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• ß-glucan in wound healing
• Ri ???

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Wound healing
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ß-glucan

• a fiber-type complex sugar (polysaccharide)
  derived from the cell wall of plants, fungi, and
  certain bacteria

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Physiology of ß-glucan

• Immunomodulator
• - activation of macrophage
• - phygocytosis of neutrophil
• - NK cell, complement system
• - activation of lymphocyte
• Lowering cholesterol level
• Modifying neoplastic disease

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Effect of ß-glucan on wound healing

• Activation of fibroblast
• - transcription factor (AP-1, Sp1, NF-?B,
  NF-1)
• ? production of PDGF-AB, FGF-ab, TGF-aß,
• VEGF, NT-3, etc.
• ? macrophage infiltration,
  reepithelialization, collagen
• deposition, increase tensile strength
• Stimulation of macrophage

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Applications of ß-glucan

• I. Effectiveness of beta-glucan collagen for
  treatment of partial-thickness burns in children
• II. Bio-artificial skin composed of gelatin and
  (1?3), (1?6)-ß-glucan

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I. ß-glucan collagen for treatment of
partial-thickness burns of children

• BGC beta-glucan collagen matrix
• BGC as a temporary wound dressing, intended for
  management of partial-thickness burns, donor
  sites, and shallow wounds

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Discussion

• Outcome of burn injuries was not affected
  adversely by the choice of BGC or standard
  treatment with silver sulfadiazine
• Advantage of BGC
• - lack of daily wound care (painful dressing)
• - provide a semiocclusive wound covering,
  decrease evaporative water and heat loss
• - effective barrier to bacterial contamination
• - allow improved physical and occupational
  therapy
• - lower financial expense

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II. Bio-artificial skin composed of gelatin and
(1?3), (1?6)-ß-glucan

• Dermal substitute
• function as a guide for cells moving into the
  repair area, serve as a scaffold, and help
  synthesize extracellular matrix (ECM)
• Porous gelatin/ß-glucan sponge containing
  fibroblast
• (gelatin denatured type of collagen,
  activating macrophages, and having hemostatic
  effect)

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Material and methods

• Sponge cultured with fibroblast artificial
  dermis
• Dermal equivalent cultured with keratinocyte
  artificial epidermis
• Animal test
• - full-thickness wound, 1cm in diameter, on
  the back of mice
• - HE stain of the wound tissue after 1 week

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Result (1)

• Cellular attachment and proliferation

Gel 100 Gg91
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Result (2)

• Morphology of scaffolds

Gel 100
Gg 91
Gg 73
Gg 55
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Result (3)

• Distribution of fibroblast for 2 weeks

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Result (4)

• Massons trichrome staining for extracellular
  matrix (ECM) of Gg91 with fibroblasts

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Result (5)

• Keratinocytes and fibroblasts cultured in Gg91
  sponge

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Result (6)

• HE stain of mouse skin wound

Gel 100
Gg 55
Gel 100 without fibroblasts
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Discussion (1)

• Cell attachment and proliferation depend on the
  contact angle, the charge on the material
  surface, functional groups, and the surface
  texture
• - Moderate contact angle
• controlled by mixing the appropriate ratios
  of gelatin andß-glucan
• - Positive charge of acidic residues of gelatin
• - Arginine-glycine-aspartic acid (RGD) group of
  gelatin
• binding with integrin receptor, promoting
  adhesion, regulating cell growth, differentiation
• ? Gel 100 Gg91 are good for cell attachment and
  proliferation

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Discussion (2)

• ß-glucan
• - modification of hydrophilic state
• - modification of pore morphology
• - bioacitve wound healing
• Gelatin
• - promote wound healing
• - form a dense surface (protection from
  evaporation from the wound, while having a
  detrimental effect on cell migration) ? low
  concentration (0.7 wt)

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Discussion (3)

• Fibroblasts in dermal equivalent
• - stimulate epidermal differentiation
• - release cytokines, accelerating the healing
  process
• - enhance the attachment of keratinocyte
• ? improve the re-epithelialization on the
  full-thickness defect

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Conclusion

• ß-glucan promotes wound healing by activation of
  macrophages and fibroblasts
• Bio-artificial skin containg ß-glucan

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Reference

• Kougias P, Wei D, Rice PJ, Ensley HE, Kalbfleisch
  J, Willams DL, Browder IW. Normal human
  fibroblasts express pattern recognition receptors
  for fungal (1?3)-ß-D-glucans. Infect Immunity
  693933-3938, 2001
• Delatte SJ, Evans J, Hebra A, Adamson W, Othersen
  HB, Tagge EP. Effectiveness of beta-glucan
  collagen for treatment of partial-thickness burns
  in children. J Pediatr Surg 36113-118, 2001.
• Wei D, Williams D, Browder W. Activation of AP-1
  and SP1 correlates with eound growth factor gene
  expression in glucan-treated human fibroblasts.
  Int Immunopharmacology 21163-1172, 2002a
• Wei D, Zhang L, Williams D, Browder W. Glucan
  stimulates human dermal fibroblast collagen
  biosythesis through a nuclear factor-1 depenent
  mechanism . Int Immunopharmacology 10161-168,
  2002b
• Lee SB, Jeon HW, Lee YW, Lee YM, Song KW, Park
  MH, Nam YS, Ahn HC Bio-artifical skin composed of
  gelatin and (1? 3),(1?6)-ß-glucan . Biomaterials
  242503-2511, 2003.
• Pillai, R. Redmond, M. Röding, J. Anti-Wrinkle
  Therapy Significant New Findings in the
  Non-Invasive Cosmetic Treatment of Skin Wrinkles
  with Beta-Glucan. Int. journal of cosmetic
  science, Volume 27, Number 5, October 2005, pp.
  292-292(1)