Wang Yiwei, Simanainen Ulla, Cheer Kenny, Suarez Francia G, Gao Yan Ru, Li Zhe, Handelsman David, Maitz Peter
Burns and Reconstructive Surgery Unit, Burns Research Group and Andrology Group, ANZAC Research Institute, University of Sydney, Concord, Australia.
Burns and Reconstructive Surgery Unit, Burns Research Group and Andrology Group, Concord Repatriation General Hospital, Concord, Australia.
Wound Repair Regen. 2016 May;24(3):478-88. doi: 10.1111/wrr.12420. Epub 2016 May 6.
The aims of this work were to define the role of androgens in female wound healing and to develop and characterize a novel wound dressing with antiandrogens. Androgens retard wound healing in males, but their role in female wound healing has not been established. To understand androgen receptor (AR)-mediated androgen actions in male and female wound healing, we utilized the global AR knockout (ARKO) mouse model, with a mutated AR deleting the second zinc finger to disrupt DNA binding and transcriptional activation. AR inactivation enhanced wound healing rate in males by increasing re-epithelialization and collagen deposition even when wound contraction was eliminated. Cell proliferation and migration in ARKO male fibroblasts was significantly increased compared with wild-type (WT) fibroblasts. However, ARKO females showed a similar healing rate compared to WT females. To exploit local antiandrogen effects in wound healing, while minimizing off-target systemic effects, we developed a novel electrospun polycaprolactone (PCL) scaffold wound dressing material for sustained local antiandrogen delivery. Using the antiandrogen hydroxyl flutamide (HF) at 1, 5, and 10 mg/mL in PCL scaffolds, controlled HF delivery over 21 days significantly enhanced in vitro cell proliferation of human dermal fibroblasts and human keratinocytes. HF-PCL scaffolds also promoted in vivo wound healing in mice compared with open wounds but not to PCL scaffolds.
这项工作的目的是确定雄激素在女性伤口愈合中的作用，并开发和表征一种含抗雄激素的新型伤口敷料。雄激素会延缓男性伤口愈合，但其在女性伤口愈合中的作用尚未明确。为了解雄激素受体（AR）介导的雄激素在男性和女性伤口愈合中的作用，我们利用了全球AR基因敲除（ARKO）小鼠模型，其AR发生突变，缺失第二个锌指以破坏DNA结合和转录激活。即使消除伤口收缩，AR失活也通过增加再上皮化和胶原蛋白沉积提高了男性的伤口愈合速度。与野生型（WT）成纤维细胞相比，ARKO雄性成纤维细胞的细胞增殖和迁移显著增加。然而，ARKO雌性与WT雌性的愈合速度相似。为了在伤口愈合中利用局部抗雄激素作用，同时尽量减少非靶向全身作用，我们开发了一种新型的电纺聚己内酯（PCL）支架伤口敷料材料，用于持续局部抗雄激素递送。在PCL支架中使用1、5和10mg/mL的抗雄激素氟他胺（HF），在21天内控制HF递送显著增强了人皮肤成纤维细胞和人角质形成细胞的体外细胞增殖。与开放性伤口相比，HF-PCL支架也促进了小鼠的体内伤口愈合，但与PCL支架相比则不然。
