title: Poly-N-acetyl glucosamine fibers induce angiogenesis in ADP inhibitor-treated diabetic mice.
abstract: BACKGROUND
  It has been previously demonstrated that short-fiber poly-N-acetyl-glucosamine (sNAG) nanofibers specifically interact with platelets, are hemostatic, and stimulate diabetic wound healing by activating angiogenesis, cell proliferation, and reepithelialization. Platelets play a significant physiologic role in wound healing. The influence of altered platelet function by treatment with the ADP inhibitor Clopidogrel (CL) on wound healing and the ability of sNAG to repair wounds in diabetic mice treated with CL were studied.
  
  
  METHODS
  Dorsal 1 cm2 skin wounds were excised on genetically diabetic 8-week to 12-week-old, Lep/r-db/db male mice, and wound healing kinetics were determined. Microscopic analysis was performed for angiogenesis (PECAM-1) and cell proliferation (Ki67). Mice were either treated with CL (P2Y12 ADP receptor antagonist, CL) or saline solution (NT). CL wounds were also treated with either a single application of topical sNAG (CL-sNAG) or were left untreated (CL-NT).
  
  
  RESULTS
  CL treatment did not alter wound healing kinetics, while sNAG induced faster wound closure in CL-treated mice compared with controls. CL treatment of diabetic mice caused an augmentation of cell proliferation and reduced angiogenesis compared with nontreated wounds. However, sNAG reversed the effects of CL on angiogenesis and partially reversed the effect on cell proliferation in the wound beds. The sNAG-treated wounds in CL-treated mice showed higher levels of cell proliferation and not did inhibit angiogenesis.
  
  
  CONCLUSIONS
  CL treatment of diabetic mice decreased angiogenesis and increased cell proliferation in wounds but did not influence macroscopic wound healing kinetics. sNAG treatment did not inhibit angiogenesis in CL-treated mice and induced faster wound closure; sNAG technology is a promising strategy to facilitate the healing of complex bleeding wounds in CL-treated diabetic patients.
authors.affiliation: Department of Plastic Surgery, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
authors.forename: Saja S
authors.initials: SS
authors.lastname: Scherer
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pietramaggiori
authors.forename: Jasmine C
authors.initials: JC
authors.lastname: Matthews
authors.forename: Anthony
authors.initials: A
authors.lastname: Gennaoui
authors.forename: Marina
authors.initials: M
authors.lastname: Demcheva
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Fischer
authors.forename: C Robert
authors.initials: CR
authors.lastname: Valeri
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Orgill
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000077144:Clopidogrel; D048909:Diabetes Complications / Q000150:complications / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057139:Nanofibers; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; C113831:poly-N-acetyl glucosamine; D000077144:Clopidogrel; D013988:Ticlopidine; D000117:Acetylglucosamine