Dr Huaikai Shi1, Dr Kevin H.-Y. Tsai1, Mr Duncan Ma1, Dr Xiaosuo Wang1, Dr Reena Desai1, Miss Roxanne Parungao1, Dr Nicholas Hunt1, A Prof Yuen Yee Cheng4, Dr Ulla Simanainen1, Prof Mark Cooper1,2, Prof David Handlesman1,2, Dr Peter Maitz2, Prof Yiwei Wang3
1USYD, Sydney, Australia, 2Concord Hospital , Concord, Australia, 3Jiangsu Provincial Engineering Research Centre of TCM External Medication Development and Application, Nanjing, China, 4UTS, Sydney, Australia
Abstract:
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. The 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 the complex role of androgens in burn wound healing and open novel therapeutic avenues for treating severe burn patients.
Biography:
Dr Huaikai Shi’s PhD work is predominately in the area of animal models, endocrinology, immunology, and bioengineering. The finding of pure androgen, dihydrotestosterone has the potential to translate into a new therapy replacing oxandrolone (which can cause liver toxicity) in treating severe burn injury patients.