RESUMEN
The decline of urethral function with advancing age plays a major role in urinary incontinence in women, impairing quality of life and economically burdening the health care system. However, none of the current urinary incontinence treatments address the declining urethral function with aging, and the mechanisms by which aging impacts urethra physiology remain little known or explored. Here, we have compared functional, morphometric, and global gene expression of urethral tissues between young and old female mice. Bladder leak point pressure (LPP) measurement showed that the aged female mice had 26.55% lower LPP compared to younger mice. Vectorized Scale-Invariant Pattern Recognition (VIPR) analysis of the relative abundance of different tissue components revealed that the mid-urethra of old female mice contains less striated muscle, more extracellular matrix/fibrosis, and diminished elastin fibers ratio compared to young mice. Gene expression profiling analysis (bulk RNA-seq of the whole urethra) showed more down-regulated genes in aged than young mice. Immune response and muscle-related (striated and smooth) pathways were predominantly enriched. In contrast, keratinization, skin development, and cell differentiation pathways were significantly downregulated in aged urethral tissues compared to those from young female mice. These results suggest that molecular pathways (i.e., ACVR1/FST signaling and CTGF/TGF-ß signaling) leading to a decreased striated muscle mass and an increase in fibrous extracellular matrix in the process of aging deserve further investigation for their roles in the declined urethral function.
RESUMEN
Ureteral stent encrustation significantly limits indwelling time and can lead to downstream urological problems. However, no ideal polymeric biomaterials have been shown to completely resist encrustation in long-term urine exposure. Recently, 2-hydroxyethyl methacrylate (HEMA)-coated Pellethane was reported as a promising biomaterial resistant to encrustation. This study compared HEMA-coated Pellethane to commercially available stents under two different artificial urine environments. To evaluate the degree and composition of encrustation on HEMA-coated Pellethane, Boston Scientific Tria, Bard InLay Optima, Cook Universa Hydrogel, and Cook Black Silicone stents were used at various dwelling times in two different artificial urine environments. In a batch-flow model, samples of stents were suspended in an artificial urine solution (AUS) at 37 °C. Every 24 h for 11 weeks, 50% of the AUS would be replaced with fresh components using a programmable peristaltic pump system. The stent materials were removed at suitable time intervals and air-dried for 24 h under sterile conditions before follow-up analysis. SEM was used to assess the degree of encrustation, and inductively coupled plasma mass spectrometry (ICP-MS) was employed to quantify the encrusted compositions, specifically for calcium, magnesium, and phosphorus. We measured the weight gain over time due to encrusted deposits on the stents and quantified the amount of Ca, Mg, and P deposited on each encrusted stent. After the 11 week trial, HEMA-coated Pellethane showed the most average mass change. SEM showed that HEMA-coated Pellethane was fully encrusted in just 2 weeks in the AUS environments, and ICP-MS showed that Ca is the most abundant deposit. Among all the tested stents, Black Silicone performed the best. The two AUSs were formulated to encrust more rapidly than physiological conditions. HEMA-coated Pellethane is not an ideal stent material, while silicone is a promising material for advancing ureteral stents.