title: Androgen actions in mouse wound healing: Minimal in vivo effects of local antiandrogen delivery.
abstract: 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.
authors.affiliation: Burns and Reconstructive Surgery Unit, Burns Research Group and Andrology Group, ANZAC Research Institute, University of Sydney, Concord, Australia.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Burns and Reconstructive Surgery Unit, Burns Research Group and Andrology Group, ANZAC Research Institute, University of Sydney, Concord, Australia.
authors.forename: Ulla
authors.initials: U
authors.lastname: Simanainen
authors.affiliation: Burns and Reconstructive Surgery Unit, Burns Research Group and Andrology Group, ANZAC Research Institute, University of Sydney, Concord, Australia.
authors.forename: Kenny
authors.initials: K
authors.lastname: Cheer
authors.affiliation: Burns and Reconstructive Surgery Unit, Burns Research Group and Andrology Group, ANZAC Research Institute, University of Sydney, Concord, Australia.
authors.forename: Francia G
authors.initials: FG
authors.lastname: Suarez
authors.affiliation: Burns and Reconstructive Surgery Unit, Burns Research Group and Andrology Group, ANZAC Research Institute, University of Sydney, Concord, Australia.
authors.forename: Yan Ru
authors.initials: YR
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: Burns and Reconstructive Surgery Unit, Burns Research Group and Andrology Group, ANZAC Research Institute, University of Sydney, Concord, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Handelsman
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Maitz
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D062326:Re-Epithelialization / Q000187:drug effects; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000473:pathology*
chemical_list: D000726:Androgen Antagonists; D003094:Collagen