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

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. 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.

Assessing the Biocompatibility and Regeneration of Electrospun‐Nanofiber Composite Tracheal Grafts

“…PGA and PLCL have been used as a vehicle for cell therapy or bioactive factors to promote repair. [22][23][24][25] For example, to improve vascularization or treat stenosis that occurred in previous studies, VEGF and Mitomycin C can be added to the polymers. [26][27][28][29] We demonstrated that these materials can be easily implanted and demonstrate early revascularization, facets which are imperative in future use as therapeutic solutions being in close proximity to areas of wound repair and regeneration.…”

“…We found that the resorbable biomaterials in CTG did not attenuate tracheal neotissue formation. PGA and PLCL have been used as a vehicle for cell therapy or bioactive factors to promote repair 22–25 . For example, to improve vascularization or treat stenosis that occurred in previous studies, VEGF and Mitomycin C can be added to the polymers 26–29 .…”