Lipid mediator profile of burn wound healing: Acellular cod fish skin grafts promote the formation of EPA and DHA derived lipid mediators during the first seven days

The use of acellular fish skin grafts (FSG) for the treatment of burn wounds is becoming more common due to its beneficial wound healing properties. In our previous study we demonstarted that FSG is a scaffold biomaterial that is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) conjugated to phosphatidylcholines. Here we investigated whether EPA and DHA derived lipid mediators are influenced during the healing of burn wounds treated with FSG. Deep partial and full thickness burn wounds (DPT and FT respectively) were created on Yorkshire pigs (n=4). DPT were treated with either FSG or fetal bovine dermis while FT were treated either with FSG or cadaver skin initially and followed by a split thickness skin graft. Punch biopsies were collected on days 7, 14, 21, 28 and 60 and analysed in respect of changes to approximately 45 derivatives of EPA, DHA, arachidonic acid (AA), and linoleic acid (LA) employing UPLC-MS/MS methodology. Several EPA and DHA derivatives, including 18-HEPE and 17-HDHA, were significantly higher on day 7 in the DPT when treated with FSG. A similar but non-significant trend was observed for the FT. In addition, prostaglandin F2α and its 15-keto derivative (AA pathway) as well as 13-HODE and 13-HOTrE (LA pathway) were significantly lower in the FSG treated FT. The results suggest that the use of FSG in burn wound treatment can alter the formation of EPA and DHA mono hydroxylated lipid mediators in comparison to other grafts of mammalian origin. The differences observed during the first seven days after treatment indicates that FSG affects the early stages of wound healing. Highlights ### Competing Interest Statement The authors have declared no competing interest. * AA : arachidonic acid wwDHA : docosahexaenoic acid DPT : deep partial thickness burn wounds EPA : eicosapentaenoic acid FSG : acellular cod fish skin grafts FT : full thickness burn wounds HETE : hydroxy- eicosatetraenoic acids KETE : keto- eicosatetraenoic acids LA : linoleic acid MeOH : methanol NSI : normalized standard intensity RvD1 : Resolvin D1 SPMs : specialized pro-resolving lipid mediators ω3-FA : omega-3 fatty acids