Stress urinary incontinence (SUI), defined by the International Continence Society (ICS) as "the complaint of involuntary loss of urine during exertion or physical activity (e.g. exercise), sneezing or coughing", is a very common complaint. The main pathogenic processes in SUI are urethral hypermobility and intrinsic sphincter deficiency (ISD). In patients with ISD, urethral injection therapies are used, which have a bulking effect on the urethral mucosa. Due to their low risk and minimal invasiveness, urethral bulking agents (UBAs) are receiving increasing attention. In this study, we develop a novel injectable bulking agent consisting of uniformly dispersed hydroxyapatite microspheres and hyaluronic acid hydrogel (HAP/HA) and evaluate its efficacy in SUI.

The morphology of the injectable filler was observed using a light microscope and a scanning electron microscope (SEM). The viability of human bladder smooth muscle cells (hSMCs) was used to assess the cytotoxicity of the agent using the CCK8 assay. A rat model of vaginal distension (VD) induced SUI was established. 20 female Sprague-Dawley rats were randomized into four groups: sham injury; VD alone; VD + saline; VD followed by periurethral injection of the bulking agent (VD + HAP/HA). At 1 week after VD or sham injury, all rats underwent abdominal leak point pressure (aLPP) assessment.

The size of composite particles was 335.43 - 79.61 µm in the injectable bulking agent. And the hydroxyapatite microspheres were uniformly dispersed in the light cross-linked hyaluronic acid hydrogel, avoiding the dispersion and agglomeration problems during injection (Fig. 1). In vitro, the filler showed excellent biocompatibility with hSMCs. In vivo, aLPP was significantly decreased 1 week after VD compared to sham injury [mean (SD) 14.92 (1.78) cmH2O vs 28.65 (2.403) cmH2O; P < 0.05]. The aLPP was significantly higher 1 week after VD + HAP/HA compared to VD + saline [23.20 (3.76) cmH2O vs 13.93 (1.199) cmH2O; P < 0.05], demonstrating an excellent bulking effect even 1 week after VD (Fig. 2). This agent also promoted cell infiltration at the injection site.

In this novel bulking agent, HA, which was an important component of extracellular matrix (ECM), was chosen as the carrier of HAP particles compared to Coaptite. It was biocompatibility, bioactive and effective in the treatment of SUI.

In summary, we present a novel injectable cross-linked compound bulking agent with biocompatibility, bioactive and stable properties for the treatment of SUI. It has a promising clinical application, but detailed and long-term studies in animal models are needed.

Continence 7S1 (2023) 100769
DOI: 10.1016/j.cont.2023.100769