Vaginal childbirth causes significant pelvic floor trauma in women. Maternal childbirth injury is the leading risk factor for pelvic floor muscle disorders (PFDs) including urinary incontinence (UI) and Pelvic Organ Prolapse (POP). Although the damage occurs during childbirth, its impact is often seen much later in life when women start developing symptoms of POP such as a vaginal bulge or a dragging sensation, and bladder, bowel, and sexual dysfunction that impacts 1 in 4 women across all ages. At present, there is no optimal therapy or surgical intervention for POP treatment given the high failure rates of native tissue repair. Even after 12 years, PFDs such as UI persists in 75% of women as a result of vaginal delivery, highlighting the need for newer strategies for combating PFDs. The development of new therapies for maternal birth injuries are largely limited due to the lack of a suitable large animal model that mimics human birth. Rather than wait for the majority of women to develop POP at menopause, we propose to develop a prophylactic therapy for POP to be injected soon after childbirth by delivering mesenchymal stem cells from their endometrium in a novel nanogel.

Herein, we selected virgin sheep and simulated birth injury using a water balloon catheter that is clinically used to mitigate post-partum uterine bleeding. Autologous endometrial Mesenchymal stem cells (eMSCs) were obtained from uterine biopsies from sheep following a hysterectomy.  The cells were purified to CD271+ and CD49f-  and cultured on short degradable polymeric nanofibers suspended in gelatin gel (NanoGel) and transplanted after 30 days of simulated vaginal birth injury. Sheep transplanted with nanogel without eMSCs and sham injury served as control. After another 30days of observation, vaginal laxity was measured and whole vaginas were explanted and histologically assessed using electron microscopy, histology stains and immunohistochemistry.

We observed that birth injury in virgin sheep is characterised by disruption of collagen, smooth muscle cells and elastin content within the vaginal tissue. However, an injection of eMSC nanogel treatment after simulated injury could reverse these alternations. Furthermore, eMSC based therapy promoted angiogenesis as some cells were retained up to 30 days without triggering unwanted foreign body response.

With the rising ageing population, POP represents a significant concern and healthcare burden due to the lack of an optimal long-term solution. In this study, we report the first ovine model of birth injury and explore the possibility of repairing vaginal damage soon after birth injury, as a strategy to promote early healing to prevent progression to POP.

This study further assessed a simple autologous tissue engineered biosystem to repair and reverse childbirth induced vaginal injuries, thus providing a major women’s health problem of society.