The role of androgens in burn injury wound healing

Yiwei Wang1, Brenton R Condor2, Brian Lesmana3, Roxanne Parungao4, Franica Garces Suarez5, Zhe Li6, Ulla Simanainen7, David Handelsman8 , Mark Cooper9 and Peter Maitz10

 Burns Research, ANZAC Research Institute, The University of Sydney, NSW, 2137; yiweiwang@anzac.edu.au
1. Burns Research, ANZAC Research Institute, The University of Sydney, NSW, 2137; bcon5353@uni.sydney.edu.au
2. Burns Research, ANZAC Research Institute, The University of Sydney, NSW, 2137; bles5603@uni.sydnedy.edu.au
3. Burns Research, ANZAC Research Institute, The University of Sydney, NSW, 2137; rpar4161@uni.sydney.edu.au
4. Burns Research, ANZAC Research Institute, The University of Sydney, NSW, 2137; francia.suarez@sydney.edu.au
5. Burns Unit, Concord Repatriation General Hospital, Concord, NSW, 2137; zhe.li@sswahs.nsw.gov.au
6. Andrology, ANZAC Research Institute, The University of Sydney, NSW, 2137; usimanainen@anzac.edu.au
7. Andrology, ANZAC Research Institute, The University of Sydney, NSW, 2137; djh@anzac.edu.au
8. Adrenal Steroid, ANZAC Research Institute, The University of Sydney, NSW, 2137; mark.cooper@sydney.edu.au
9. Burns Unit, Concord Repatriation General Hospital, Concord, NSW, 2137; Burns Research, ANZAC Research Institute, The University of Sydney, NSW, 2137; peter.maitz@sydney.edu.au
Rational: Androgens, acting via androgen receptor (AR), inhibit cutaneous wound repair in men and male mice. In contrast, recent clinical studies have reported that testosterone and an androgen analog (Oxandrolone) promotes healing of burn injuries. This finding points to a contradictory and context-dependent role of androgens in wound healing that differ between burn injury and simple incisional skin wound healing.

Objective: The aim of this study was to investigate how AR-mediated androgen actions modify the complex burn injury wound healing.

Methods:
A mouse burn injury model was established to create the accompanying hypermetabolic-catabolic state. Mice were subjected to a thermal injury from a hot brass rod (4cm2) constituting a severe large burn. After 48 hrs following thermal injury, the wound site was debrided to remove damaged skin and to avoid infection prior to wound dressing. Following the injuries, mice were weighed daily, and metabolic changes, lean mass and muscle wasting were assessed to determine if androgens via AR modify the catabolic state that develops after burns injury. Wound healing rate, epidermal migration and healing processes were also analysed.

Results:
Our preliminary study showed that burn wounds in all mice caused systemic hypermetabolism syndrome and continued weight lost and muscle wasting over 7 days. We found that androgens acting via AR significantly promote wound healing post thermal injury. In AR knockout mice, burn wound repair was markedly delayed with ~70% wound area remaining unhealed after 7 days compared to wild type mice. Moreover, AR knock out significantly reduced re-epithelialisation with very limited keratinocytes proliferation.

Key Words
Androgens, burn injury, wound healing, mouse model

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