Estrogen replacement promotes cutaneous wound healing in 8–10-week young ovariectomized female mice. However, research using aged ovariectomized female mice has not been reported, to the best of our knowledge. Therefore, we investigated the effect of 17β-estradiol on cutaneous wound healing using 24-week middle-aged ovariectomized female mice. Twenty-week-old female mice were divided into three groups: medication with 17β-estradiol after ovariectomy (OVX + 17β-estradiol), ovariectomy (OVX), and sham (SHAM). After 4 weeks, the mice received two full-thickness wounds. Then, the OVX + 17β-estradiol group was administered 17β-estradiol at 0.01？g/day until healing. The ratio of wound area in the OVX + 17β-estradiol group was significantly decreased compared with that in the OVX group. The numbers of neutrophils and macrophages in the OVX + 17β-estradiol group were significantly smaller than those in the OVX group. In addition, the ratio of myofibroblasts in the OVX + 17β-estradiol group was significantly higher than that in the OVX group. These data suggested that exogenous continuous 17β-estradiol administration promotes cutaneous wound healing in 24-week OVX female mice by reducing wound area, shortening inflammatory response, and promoting wound contraction. However, it is unclear whether the effect of exogenous estrogen on wound healing outweighs the delay of wound healing due to advanced age. 1. Introduction Cutaneous wound healing is a complex, tightly orchestrated response to injury, carefully regulated at temporal and spatial levels [1]. Generally, there are various overlapping phases of the repair process (the immediate response; the inflammatory response; the proliferation, migration, and contraction phase; and the remodeling phase) [1]. With advanced age, this series of events becomes disrupted and healing is delayed. In elderly humans, delayed healing of acute wounds is characterized by the extension of inflammation [2], increased protease activity [3, 4], and delayed re-epithelialization [5]. However, postmenopausal women with systemically reduced estrogen heal poorly [5], whereas exogenous estrogen treatment reverses this delayed cutaneous wound healing by dampening excessive neutrophil recruitment [6], promoting re-epithelialization [5] and increasing collagen deposition [5–7]. Rodent models subjected to ovariectomy (OVX) constitute a cornerstone in elucidation of the effects and detailed biological mechanisms of estrogen. OVX exhibited delayed cutaneous wound healing compared with SHAM [5, 6, 8–14], whereas exogenous estrogen treatment
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