Biomarkers of Skin Graft Healing in Venous Leg Ulcers

Klaus Kirketerp-Møller, Petra Doerfler, Nicole Schoefmann, Barbara Wolff-Winiski, Omid Niazi, Vibeke Pless, Tonny Karlsmark, Magnus S. Ågren


There is a need for biomarkers that predict the success of transplantation of venous leg ulcers (with autologous split-thickness skin grafts). The primary objective of this exploratory study was to investigate the association between split-thickness skin graft healing in venous leg ulcers and candidate wound fluid biomarkers representing inflammatory cell and endogenous proteinase activities, and bioactivity. A secondary objective was to compare biomarker levels of the 17 venous leg ulcers with sterile split-thickness skin graft donor-site wounds in another 10 patients with venous leg ulcers. Wound fluids were collected for 24 h using a validated method. The concentration of preoperative matrix metalloproteinase-9 in wound fluid was higher in venous leg ulcers showing good healing (n = 10) than in venous leg ulcers showing poor healing (n = 7) 12 weeks after transplantation with meshed split-thickness skin grafts. The diagnostic value of matrix metalloproteinase-9 was good according to receiver-operating characteristic curve analysis. Matrix metalloproteinase activity in wound fluids from split-thickness skin graft donor-site wounds increased as a function of time and healing, but was still lower than matrix metalloproteinase activity in venous leg ulcer wound fluids, which showed increased levels of most biomarkers except for matrix metalloproteinase-9 and matrix metalloproteinase-2. In conclusion, wound fluid matrix metalloproteinase-9 concentration is a potential predictive biomarker of split-thickness skin graft healing in venous leg ulcers.

Original languageEnglish
Article numberadv00749
JournalActa Dermato-Venereologica
Pages (from-to)adv00749
Publication statusPublished - 7 Jul 2022


  • Biomarkers/analysis
  • Humans
  • Leg Ulcer/surgery
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinases
  • Skin Transplantation
  • Varicose Ulcer/diagnosis
  • Wound Healing


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