Estradiol-17β [E₂] stimulates wound healing in a 3D in vitro tissue-engineered vaginal wound model

Childbirth contributes to common pelvic floor problems requiring reconstructive surgery in postmenopausal women. Our aim was to develop a tissue-engineered vaginal wound model to investigate wound healing and the contribution of estradiol to pelvic tissue repair. Partial thickness scalpel wounds were made in tissue models based on decellularized sheep vaginal matrices cultured with primary sheep vaginal epithelial cells and fibroblasts. Models were cultured at an airliquid interface (ALI) for 3 weeks with and without estradiol-17β [E₂]. Results showed that E₂ significantly increased wound healing and epithelial maturation. Also, E₂ led to collagen reorganization after only 14 days with collagen fibers more regularly aligned and compactly arranged Additionally, E₂ significantly downregulated α-SMA expression which is involved in fibrotic tissue formation. This model allows one to investigate multiple steps in vaginal wound healing and could be a useful tool in developing therapies for improved tissue healing after reconstructive pelvic floor surgery.