Controlled dual release of dihydrotestosterone and flutamide from polycaprolactone electrospun scaffolds accelerate burn wound healing.
Shi, H
Tsai, KH-Y
Ma, D
Wang, X
Desai, R
Parungao, RJ
Hunt, NJ
Cheng, YY
Zhang, H
Xu, Y
Simanainen, U
Tan, Q
Cooper, MS
Handelsman, DJ
Maitz, PK
Wang, Y
- Publisher:
- Wiley
- Publication Type:
- Journal Article
- Citation:
- FASEB J, 2022, 36, (5), pp. e22310
- Issue Date:
- 2022-05
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Full metadata record
| Field | Value | Language |
|---|---|---|
| dc.contributor.author | Shi, H | |
| dc.contributor.author | Tsai, KH-Y | |
| dc.contributor.author | Ma, D | |
| dc.contributor.author | Wang, X | |
| dc.contributor.author | Desai, R | |
| dc.contributor.author | Parungao, RJ | |
| dc.contributor.author | Hunt, NJ | |
| dc.contributor.author | Cheng, YY | |
| dc.contributor.author | Zhang, H | |
| dc.contributor.author | Xu, Y | |
| dc.contributor.author | Simanainen, U | |
| dc.contributor.author | Tan, Q | |
| dc.contributor.author | Cooper, MS | |
| dc.contributor.author | Handelsman, DJ | |
| dc.contributor.author | Maitz, PK | |
| dc.contributor.author | Wang, Y | |
| dc.date.accessioned | 2023-04-13T02:33:55Z | |
| dc.date.available | 2022-03-29 | |
| dc.date.available | 2023-04-13T02:33:55Z | |
| dc.date.issued | 2022-05 | |
| dc.identifier.citation | FASEB J, 2022, 36, (5), pp. e22310 | |
| dc.identifier.issn | 0892-6638 | |
| dc.identifier.issn | 1530-6860 | |
| dc.identifier.uri | http://hdl.handle.net/10453/169727 | |
| dc.description.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. | |
| dc.format | ||
| dc.language | eng | |
| dc.publisher | Wiley | |
| dc.relation.ispartof | FASEB J | |
| dc.relation.isbasedon | 10.1096/fj.202101803R | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.subject | 0601 Biochemistry and Cell Biology, 0606 Physiology, 1116 Medical Physiology | |
| dc.subject.classification | Biochemistry & Molecular Biology | |
| dc.subject.mesh | Androgen Antagonists | |
| dc.subject.mesh | Androgens | |
| dc.subject.mesh | Animals | |
| dc.subject.mesh | Burns | |
| dc.subject.mesh | Dihydrotestosterone | |
| dc.subject.mesh | Flutamide | |
| dc.subject.mesh | Humans | |
| dc.subject.mesh | Mice | |
| dc.subject.mesh | Polyesters | |
| dc.subject.mesh | Tissue Scaffolds | |
| dc.subject.mesh | Wound Healing | |
| dc.subject.mesh | Animals | |
| dc.subject.mesh | Humans | |
| dc.subject.mesh | Mice | |
| dc.subject.mesh | Burns | |
| dc.subject.mesh | Flutamide | |
| dc.subject.mesh | Dihydrotestosterone | |
| dc.subject.mesh | Polyesters | |
| dc.subject.mesh | Androgen Antagonists | |
| dc.subject.mesh | Androgens | |
| dc.subject.mesh | Wound Healing | |
| dc.subject.mesh | Tissue Scaffolds | |
| dc.subject.mesh | Androgen Antagonists | |
| dc.subject.mesh | Androgens | |
| dc.subject.mesh | Animals | |
| dc.subject.mesh | Burns | |
| dc.subject.mesh | Dihydrotestosterone | |
| dc.subject.mesh | Flutamide | |
| dc.subject.mesh | Humans | |
| dc.subject.mesh | Mice | |
| dc.subject.mesh | Polyesters | |
| dc.subject.mesh | Tissue Scaffolds | |
| dc.subject.mesh | Wound Healing | |
| dc.title | Controlled dual release of dihydrotestosterone and flutamide from polycaprolactone electrospun scaffolds accelerate burn wound healing. | |
| dc.type | Journal Article | |
| utslib.citation.volume | 36 | |
| utslib.location.activity | United States | |
| utslib.for | 0601 Biochemistry and Cell Biology | |
| utslib.for | 0606 Physiology | |
| utslib.for | 1116 Medical Physiology | |
| pubs.organisational-group | /University of Technology Sydney | |
| pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
| pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences | |
| utslib.copyright.status | open_access | * |
| dc.date.updated | 2023-04-13T02:33:46Z | |
| pubs.issue | 5 | |
| pubs.publication-status | Published | |
| pubs.volume | 36 | |
| utslib.citation.issue | 5 |
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.
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