Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

The role of androgens in cutaneous wound healing: impact of local drug delivery (#44)

Kenny Cheer 1 , Francia Garces Suarez 1 , Brian Lesmana 1 , Ulla Simanainen 1 , David Handelsman 1 , Peter Maitz 1 , Yiwei Wang 1
  1. Anzac Research Institute, Concord , NSW, Australia

Androgens retard wound healing in males, but their role in female wound healing has not been established. To explore the AR-mediated androgen actions in male and female wound healing, we utilized the global, androgen insensitive AR knockout (ARKO) mouse model, with a mutated AR deleting the second zinc finger to disrupt DNA binding and transcriptional activation. Cutaneous (excision) wounds of 4cm2 in size were surgically created on the dorsal area of male and female wild type (WT) and ARKO mice. Wound healing rate was measured using Visitrak Wound Measurement Grid (Smith and Nephew, Australia) over 21 days and skin biopsies of the wound area were harvested by skin excision under anaesthesia on days 3, 5, 7, 14 and 21 for histological, immunohistochemical and molecular analysis. The results showed that AR inactivation significantly enhanced wound healing rate in male mice by increasing re-epithelialization and collagen deposition. The enhanced wound healing was not due to faster contraction (wound healing in mice) in ARKO males as demonstrated using a silicone splint to stop contraction. Increased wound healing in ARKO males was supported by significantly increased proliferation of ARKO compared to WT fibroblasts. In contrast, AR in activation had no effect on wound healing rate in female mice that could be due to lower AR expression and/or endogenous androgen levels or greater role for estrogens. To exploit local anti-androgen effects in wound healing while minimizing off-target systemic effects, we developed a novel electrospun polycaprolactone (PCL) scaffold wound dressing materials for sustained local anti-androgen delivery. Using the anti-androgen hydroxyflutamide (HF) at 1, 5 and 10 mg/ml in PCL scaffolds with controlled HF delivery over 21 days significantly enhanced in vitro cell proliferation of human dermal fibroblasts (HDFs) and human keratinocytes (HKCs), and promoted in vivo wound healing in mice.