Developing physiologically relevant in vitro tissue engineered models of the vaginal mucosa for applications in vaginal tissue research

Pelvic floor disorders such as pelvic organ prolapse (POP) and stress urinary incontinence (SUI) affect 50% postmenopausal women worldwide with 11% are at a lifetime risk of surgery. There is currently a treatment gap for patients requiring surgical intervention following the ban on using polypropylene (PPL) mesh in the urogynecological reconstructive procedures in 2019 by the FDA. There is an urgent need to design better biomaterials to support the female pelvic floor and to develop suitable preclinical testing systems for these new biomaterials. This project aimed at developing physiologically relevant in vitro tissue engineered (TE) models of the vaginal mucosa to enable laboratory-based preclinical testing of existing and new biomaterials and to study the cellular response to these biomaterials in an in vitro modelling system. Tissue engineered (TE) vaginal models were developed by culturing primary sheep vaginal epithelial cells and fibroblasts on decellularised sheep vaginal tissues at an air-liquid interface (ALI) for three weeks and tested for their estradiol ‐17β [E2] responsiveness. Then wounded vaginal models were developed to study the process of vaginal wound healing and for implantation of biomaterials developed for the pelvic floor to investigate the cellular and tissue response towards these materials in the absence and presence of E2. TE vaginal models recapitulated the histological features of the native vaginal tissue and formed stratified squamous epithelia on decellularised vaginal matrices over three weeks at an ALI culture. Cellular metabolic activity and proliferation remained high and the models showed a dose‐dependent response to E2. I was able to study the time course of vaginal wound healing and the wounded models implanted with biomaterials were able to discriminate between biomaterials that were likely to cause a fibrotic tissue response (PPL) from those that caused tissue remodelling (PU Z3) in vitro. In summary, these models showed promising results as preclinical testing models and can contribute towards the development and testing of novel biomaterials designed for the female pelvic floor repair.