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Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model

Authors

  • Stefan Bohr MD, PhD,

    1. Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, the Shriners Bruns Hospital, Boston, Massachusetts
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  • Suraj J Patel PhD,

    1. Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, the Shriners Bruns Hospital, Boston, Massachusetts
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  • Dhruv Sarin BS,

    1. Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, the Shriners Bruns Hospital, Boston, Massachusetts
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  • Daniel Irimia MD, PhD,

    1. Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, the Shriners Bruns Hospital, Boston, Massachusetts
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  • Martin L. Yarmush MD, PhD,

    1. Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, the Shriners Bruns Hospital, Boston, Massachusetts
    2. Department of Biomedical Engineering, Rutgers University, New Brunswick, New Jersey
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  • Francois Berthiaume PhD

    Corresponding author
    1. Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, the Shriners Bruns Hospital, Boston, Massachusetts
    2. Department of Biomedical Engineering, Rutgers University, New Brunswick, New Jersey
    • Reprint requests:

      Mr. Francois Berthiaume, Department of Biomedical Engineering, 599 Taylor Road, Piscataway, NJ 08854, USA.

      Tel: +848-445-6566;

      Fax: +732-445-3753;

      Email: fberthia@rci.rutgers.edu

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Abstract

Deep partial thickness burns are subject to delayed necrosis of initially viable tissues surrounding the primary zone of thermally induced coagulation, which results in an expansion of the burn wound, both in area and depth, within 48 hours postburn. Neutrophil sequestration and activation leading to microvascular damage is thought to mediate this secondary tissue damage. Resolvins, a class of endogenous mediators derived from omega-3 polyunsaturated fatty acids, have been shown to regulate the resolution of inflammation. We hypothesized that exogenous resolvins could mitigate the deleterious impact of the inflammatory response in burn wounds. Using two different mouse burn injury models involving significant partial thickness injuries, we found that a systemically administered single dose of resolvin D2 (RvD2) as low as 25 pg/g bw given within an interval of up to 4 hours postburn effectively prevented thrombosis of the deep dermal vascular network and subsequent dermal necrosis. By preserving the microvascular network, RvD2 enhanced neutrophil access to the dermis, but prevented neutrophil-mediated damage through other anti-inflammatory actions, including inhibition of tumor necrosis factor-α, interleukin-1β, and neutrophil platelet–endothelial cell adhesion molecule-1. In a clinical context, RvD2 may be therapeutically useful by reducing the need for surgical debridement and the area requiring skin grafting.

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