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Controlled dual release of dihydrotestosterone and flutamide from polycaprolactone electrospun scaffolds accelerate burn wound healing.

Huaikai ShiKevin H-Y TsaiDuncan MaXiaosuo WangReena DesaiRoxanne J ParungaoNicholas J HuntYuen Yee ChengHao ZhangYe XuUlla SimanainenQian TanMark S CooperDavid J HandelsmanPeter K MaitzYiwei Wang
Published in: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2022)
Wound healing is a complex process involving multiple independent and overlapping sequential physiological mechanisms. In addition to cutaneous injury, a severe burn stimulates physiological derangements that induce a systemic hypermetabolic response resulting in impaired wound healing. Topical application of the anti-androgen drug, flutamide accelerates cutaneous wound healing, whereas paradoxically systemic dihydrotestosterone (DHT) improves burn wound healing. We developed and characterized a PCL scaffold that is capable of controlled release of androgen (DHT) and anti-androgen (F) individually or together. This study aims to investigate whether local modification of androgen actions has an impact on burn injury wound healing. In a full-thickness burn wound healing, mouse model, DHT/F-scaffold showed a significantly faster wound healing compared with F-scaffold or DHT-scaffold. Histology analysis confirmed that DHT/F-scaffold exhibited higher re-epithelization, cell proliferation, angiogenesis, and collagen deposition. Dual release of DHT and F from PCL scaffolds promoted cell proliferation of human keratinocytes and alters the keratinocyte cell cycle. Lastly, no adverse effects on androgen-dependent organs, spleen and liver were observed. In conclusion, we demonstrated DHT plus F load PCL scaffolds accelerated burn wound healing when loading alone did not. These findings point to a complex role of androgens in burn wound healing and open novel therapeutic avenues for treating severe burn patients.
Keyphrases
  • wound healing
  • tissue engineering
  • cell proliferation
  • cell cycle
  • mouse model
  • end stage renal disease
  • chronic kidney disease
  • emergency department
  • early onset
  • signaling pathway
  • peritoneal dialysis
  • bone regeneration