Hydroxyapatite/hyaluronic acid composite hydrogel as an injectable bulking agent to treat stress urinary incontinence

Liu M1, Peng L1, Xiao Y2, Luo D1, Fan Y1

Research Type

Pure and Applied Science / Translational

Abstract Category

Female Stress Urinary Incontinence (SUI)

Abstract 51
Female Stress Urinary Incontinence
Scientific Podium Short Oral Session 8
Wednesday 27th September 2023
15:50 - 15:57
Theatre 102
Basic Science Stress Urinary Incontinence Grafts: Synthetic Pre-Clinical testing
1. Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan, 610041, P.R. China, 2. National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, 610064, China.
Presenter
Links

Abstract

Hypothesis / aims of study
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.
Study design, materials and methods
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.
Results
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.
Interpretation of results
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.
Concluding message
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.
Figure 1 Fig. 1 The morphology of the bulking agent.
Figure 2 Fig. 2 aLPP results. Each bar represents mean ± SD of data from 5 rats. *** indicates a significant difference compared with the sham injury P < 0.05.
Disclosures
Funding NONE Clinical Trial No Subjects Animal Species Rat Ethics Committee the Institutional Animal Care and Use Committee of West China Hospital of Sichuan University
Citation

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

13/11/2024 22:35:21