Effects of Poly-N-acetyl Glucosamine(pGlcNAc) Patch on Wound Healing in db/db Mouse

Poly-N-acetyl-glucosamine이 당뇨병 쥐에서 창상치료에 미치는 영향

  • Yang, Ho Jik (Department of Plastic and Reconstructive Surgery, College of Medicine, Eulji University) ;
  • Yoon, Chi Sun (Department of Plastic and Reconstructive Surgery, College of Medicine, Eulji University)
  • 양호직 (을지대학교 의과대학 성형외과학교실) ;
  • 윤치선 (을지대학교 의과대학 성형외과학교실)
  • Received : 2008.01.02
  • Published : 2008.03.10

Abstract

Purpose: Poly-N-acetyl glucosamine(PGlcNAc) nanofiber-based materials, produced by a marine microalga, have been characterized as effective hemostatic and angiogenic agents. The similarity between PGlcNAc patch and the natural extracellular matrix allows it to support new healthy tissue growth in an injured area and to encourage fluid absorption. In this study, we hypothesized that a poly-N-acetyl glucosamine fiber patch(PGlcNAc patch) may enhance wound healing in the db/db mouse. Methods: PGlcNAc patches were applied on one square centimeter, full-thickness, skin wounds in the db/db mouse model. Wounds(n=15 per group) were dressed with a PGlcNAc nanofiber patch for 1 hour(1 h), 24 hours(24 h) or left untreated(NT). After the application time, patches were removed and wounds were allowed to heal spontaneously. The rate of wound closure was evaluated by digital analysis of unclosed wound area in course of time. At day 10, wounds(n=7 per group) were harvested and quantified with immunohistochemical markers of proliferation(Ki-67) and vascularization (platelet endothelial cell adhesion molecule, PECAM-1). Results: Wounds dressed with PGlcNAc patches for 1 hour closed faster than control wounds, reaching 90% closure in 16.6 days, nine days faster than untreated wounds. Granulation tissue showed higher levels of proliferation and vascularization following 1 h treatment than the 24 h and NT groups. In addition to its hemostatic properties, the PGlcNAc material also appears to accelerate wound closure in healing-impaired genetically diabetic mice. Conclusion: This material, with its combination of hemostatic and wound healing properties, has the potential to be effective agent for the treatment of complicated wounds.

Keywords

References

  1. Jemal A, Ward E, Hao Y, Thun M: Trends in the leading causes of death in the United States, 1970- 2002. JAMA 294: 1255, 2005 https://doi.org/10.1001/jama.294.10.1255
  2. Cavanagh PR, Lipsky BA, Bradbury AW, Botek G: Treatment for diabetic foot ulcers. Lancet 366: 1725, 2005 https://doi.org/10.1016/S0140-6736(05)67699-4
  3. Falanga V: Wound healing and its impairment in the diabetic foot. Lancet 366: 1736, 2005 https://doi.org/10.1016/S0140-6736(05)67700-8
  4. Saxena V, Hwang CW, Huang S, Eichbaum Q, Ingber D, Orgill DP: Vacuum-assisted closure: microdeformations of wounds and cell proliferation. Plast Reconstr Surg 114: 1086, 2004
  5. Greene AK, Puder M, Roy R, Arsenault D, Kwei S, Moses MA, Orgill DP: Microdeformational wound therapy: effects on angiogenesis and matrix metalloproteinases in chronic wounds of 3 debilitated patients. Ann Plast Surg 56: 418, 2006 https://doi.org/10.1097/01.sap.0000202831.43294.02
  6. Fazio VW, Cohen Z, Fleshman JW, van Goor H, Bauer JJ, Wolff BG, Corman M, Beart RW Jr, Wexner SD, Becker JM, Monson JR, Kaufman HS, Beck DE, Bailey HR, Ludwig KA, Stamos MJ, Darzi A, Bleday R, Dorazio R, Madoff RD, Smith LE, Gearhart S, Lillemoe K, Gohl J: Reduction in adhesive small-bowel obstruction by Seprafilm adhesion barrier after intestinal resection. Dis Colon Rectum 49: 1, 2006 https://doi.org/10.1007/s10350-005-0268-5
  7. Pena Ede L, Sala S, Rovira JC, Schmidt RF, Belmonte C: Elastoviscous substances with analgesic effects on joint pain reduce stretch-activated ion channel activity in vitro. Pain 99: 501, 2002 https://doi.org/10.1016/S0304-3959(02)00260-9
  8. Orgill DP, Straus FH 2nd, Lee RC: The use of collagen- GAG membranes in reconstructive surgery. Ann N Y Acad Sci 888: 233, 1999 https://doi.org/10.1111/j.1749-6632.1999.tb07959.x
  9. Vournakis JN, Demcheva M, Whitson A, Guirca R, Pariser ER: Isolation, purification, and characterization of poly-N-acetyl glucosamine use as a hemostatic agent. J Trauma 57: S2, 2004 https://doi.org/10.1097/01.TA.0000136741.66698.9D
  10. Valeri CR, Srey R, Tilahun D, Ragno G: In vitro effects of poly-N-acetyl glucosamine on the activation of platelets in platelet-rich plasma with and without red blood cells. J Trauma 57: S22, 2004 https://doi.org/10.1097/01.TA.0000136744.12440.47
  11. Thatte HS, Zagarins S, Khuri SF, Fischer TH: Mechanisms of poly-N-acetyl glucosamine polymer- mediated hemostasis: platelet interactions. J Trauma 57: S13, 2004 https://doi.org/10.1097/01.TA.0000136743.12440.89
  12. Thatte HS, Zagarins SE, Amiji M, Khuri SF: Poly-N- acetyl glucosamine-mediated red blood cell interactions. J Trauma 57: S7, 2004 https://doi.org/10.1097/01.TA.0000136742.04816.38
  13. Pietramaggiori G, Kaipainen A, Czeczuga JM, Wagner CT, Orgill DP: Freeze-dried platelet-rich plasma shows beneficial healing properties in chronic wounds. Wound Repair Regen 14: 573, 2006 https://doi.org/10.1111/j.1743-6109.2006.00164.x
  14. Ikeda Y, Young LH, Vournakis JN, Lefer AM: Vascular effects of poly-N-acetylglucosamine in isolated rat aortic rings. J Surg Res 102: 215, 2002 https://doi.org/10.1006/jsre.2001.6323
  15. Pedram A, Razandi M, Hu RM, Levin ER: Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion. J Biol Chem 272: 17097, 1997 https://doi.org/10.1074/jbc.272.27.17097