Microarchitectural changes in the urethral wall after injecting hyaluronic acid based bulking agent (Zhoabex G): an experimental study in New Zealand white female rabbits

Abstract

Stress urinary incontinence (SUI) is one of the most prevalent conditions in women that has a significant adverse effect on the quality of life. There is a wide variety of surgical treatment approaches for female SUI. Although many surgical procedures are available, all are associated with procedure-related complications. Urethral bulking agents (UBA's) have been perceived as the safest alternatives in this regard due to their tissue compatibility. This prompted us to explore a potential bulking agent composed of hyaluronic acid named “Zhoabex G”. 5-months-old New Zealand white female rabbits (n = 27) weighing 2 kg ± 2.2 kg were used and divided into three equal groups: Group A (control group, n = 9) received no agent, Group B (sham group, n = 9) were injected with 0.5 ml of 10 % NaCl, and Group C (study group, n = 9) were injected with 0.5 ml of Zhoabex G (cross-linked hyaluronic acid). At the end of experiment, after 5 months, all rabbits were sacrificed under anesthesia. The urethrae were dissected from all the groups for histochemical and immunohistochemical studies to evaluate the effect of Zhoabex G (cross-linked hyaluronic acid) on the collagen content, urethral lumen diameter, epithelial thickness, extent of inflammation and vascularity in the urethral wall. Masson's trichrome stained sections revealed a mild increase in the collagen content of the submucosal layer of the urethra of Zhoabex G (cross-linked hyaluronic acid) treated group with a significant reduction in diameter of the urethral lumen and the epithelial thickness. Furthermore, immunostaining studies revealed a significant increase in the expression of CD31 antibodies (vascular endothelial cell markers) in Zhoabex G (cross-linked hyaluronic acid) treated group when compared to the control and sham groups, respectively. However, there was no statistically significant difference in the extent of inflammation in studied groups. Results of this study suggest that the Zhoabex G (cross-linked hyaluronic acid) causes a significant cooptation of the urethral lumen in female rabbits. • Stress urinary incontinence (SUI) is one of the most prevalent conditions in women. • Urethral bulking agents (UBA's) are the substances which are injected into the wall of the proximal urethra to provide bulk thus minimizing incontinence in women with SUI. • Our findings suggest that Zhoabex G (cross-linked hyaluronic acid) could be used as a biocompatible bulking agent with minimal inflammatory response and mild fibrosis.