Vaginal childbirth is the primary cause of pelvic floor disorders (PFDs), including pelvic organ prolapse (POP), which affects up to one in four women. Although obstetric trauma occurs during delivery, its sequelae manifest years later, resulting in impaired bladder, bowel, and sexual function. Current surgical and conservative interventions primarily alleviate symptoms rather than prevent disease onset. There is a critical unmet clinical need for postpartum regenerative interventions that restore pelvic tissue integrity following childbirth. Aloe Vera–Alginate hydrogel (AV-ALG-Hyd) offers a biocompatible, antioxidant, and immunomodulatory scaffold suitable for cell delivery. We hypothesised that early postpartum administration of AV-ALG-Hyd incorporating human endometrial mesenchymal stem cells (eMSC) would mitigate injury. 
The primary aim was to evaluate the regenerative efficacy of AV-ALG-Hyd ± eMSC in promoting tissue repair, improving biomechanical function, and reducing prolapse development in a preclinical ovine model of simulated vaginal birth injury.

Twenty-one primiparous ewes underwent simulated birth injury using a 300 mL Bakri balloon catheter inflated intravaginally for 15 minutes and were randomised into three groups (n=7/group): (1) injury only, (2) AV-ALG-Hyd alone, and (3) AV-ALG-Hyd + eMSC. Interventions were administered intravaginally immediately post-injury, and tissues were harvested at 30 and 90 days. Outcome measures included pelvic organ support using Pelvic Organ Prolapse Quantification (POP-Q) system, smooth muscle regeneration (α-SMA), collagen/elastin histology, angiogenic and inflammatory gene expression, and biomechanical tensile testing. All procedures were approved by an institutional Animal Ethics Committee and conducted in accordance with national guidelines.

The AV-ALG-Hyd + eMSC group demonstrated reduction in POP severity and restored smooth muscle area at 90 days. α-SMA expressions increased across groups, with mean (± SD) values rising from 16.72 ± 6.68% in injury only to 38.26 ± 3.08% in AV-ALG-Hyd + eMSC (p<0.0001). Gene expression analysis demonstrated a modest upregulation of regenerative and healing markers Acta2, Vegfa, Fgfr3, Mrc1 and downregulation of Col1a1, Col3a1 and pro-inflammatory Cd80 markers in the AV-ALG-Hyd + eMSC group compared with injury only. Biomechanical testing demonstrated enhanced functional recovery, with ultimate tensile strength increasing to 1.49 ± 0.39 MPa in the AV-ALG-Hyd + eMSC group compared with 0.93 ± 0.22 MPa in injury only controls (p<0.05).

The findings demonstrate that AV-ALG-Hyd with eMSC promotes tissue repair following simulated vaginal birth injury, with evidence of improved pelvic organ support, restoration of smooth muscle architecture, and enhanced tensile strength. These effects were accompanied by modest upregulation of regenerative and angiogenic markers and downregulation of pro-inflammatory and fibrotic markers, suggesting that the therapy may act through immunomodulation.

AV-ALG-Hyd scaffolds incorporating eMSC promote effective postpartum tissue repair, alleviate birth injury associated prolapse progression, and restore biomechanical function. This study provides the first large-animal preclinical evidence supporting a regenerative therapeutic strategy for preventing long-term pelvic floor dysfunction following childbirth injury.

Continence 19S (2026) 102587
DOI: 10.1016/j.cont.2026.102587