KL2 Scholar Scope: Development of a Bladder-on-a-Chip Device for Drug Delivery Applications

Abstract: Lower urinary tract symptoms are an understudied aspect of health and manifest during a variety of times in person’s life, such as childbearing, aging, and menopause. Lower urinary tract symptoms include conditions such as overactive bladder, recurrent urinary tract infections, interstitial cystitis, bladder pain syndrome, and others. They are common (65- 76% of non-males), costly, and bothersome, leading to embarrassment, social isolation, reduction of physical activity, a negative impact on sexual activity, mental health problems (anxiety and depression), and decreased work productivity. Many pharmacologic treatments for urinary symptoms work well in some patients but lead to serious systemic side effects (e.g., cognitive decline, brain atrophy, and retinopathy), and low patient adherence; therefore, ?nding a way to deliver them locally without systemic effects would greatly improve care. Vaginal pharmacologic delivery is a promising option. We know that locally applied vaginal estrogen improves bladder symptoms of the genitourinary syndrome of menopause, recurrent UTIs, and overactive bladder through indirect cellular, vascular, and microbiome changes; however, we have not identi?ed its direct mechanism of action on the bladder. If we could understand vagina-bladder cell-cell communication better, then we might be able to administer other bladder drugs vaginally. In this proposed project, we will use vaginal estrogen as a model to understand vagina-bladder cell-cell communication. This is the focus of early studies, with future studies extending this model beyond estrogen to develop targeted therapies for urinary symptoms. We hypothesize that vagina-bladder cell-cell communication plays a critical role in lower urinary tract function and because of this, the application of local estradiol in the vagina mitigates symptoms of urinary symptoms through changes in cell-cell communication mechanisms between the vagina and bladder. To target and test our hypothesis, we will focus on technology development of an integrated vagina and lower urinary tract on-a-chip device and benchmarking the role of estradiol in vagina-bladder cellular signaling for the duration of this KL2 award (75% effort). The research achieved in this two-year period will focus on generation of preliminary data to be used in subsequent research grant mechanisms to further fund the project.