Topical estrogen application to wounds promotes delayed cutaneous wound healing in 80-week-old female mice

Topical estrogen application to wounds is effective in promoting cutaneous wound healing. However, whether it promotes cutaneous wound healing in delayed cutaneous wound healing associated with advanced age remains to be elucidated. This study aimed to evaluate the effect of topical estrogen application to wounds in cutaneous wound healing in 80-week-old female mice. C57BL/6J female mice aged 82-85 and 12 weeks old were submitted to two full-thickness wounds. Mice were divided into four groups: aged group, topical estrogen wound treatment aged group (aged-E), vehicle wound treatment aged group (aged-vehicle), and young group. Wound healing was observed until day 14. In the aged group, wound area ratio (wound area / initial wound area) was significantly higher on days 3-14, ratio of re-epithelialization was significantly lower on day 3 and tended to be lower on day 14, and neutrophil number was significantly higher on day 7 compared with the young group. In contrast, in the aged-E group, wound area ratio was significantly smaller on days 1-14, re-epithelialization ratio was significantly higher on days 3-14, and neutrophil and macrophage number was significantly lower on days 3 and 7 compared with the aged group. These results demonstrate that topical estrogen application to wounds in 80-week-old female mice promoted cutaneous wound healing by reducing wound area and inflammatory response and promoting re-epithelialization.