A novel vascularized urethra-on-a-chip model

Abstract

The male urethra transports urine and semen. Any disease of the male urethra, hindering normal voiding or ejaculation, has a major impact on quality of life. Urethral stricture disease is common and molecular research into urethral strictures is hampered by the lack of reliable models of the human urethra. The aim of this project is to develop an in vitro model system of the human urethra. We hypothesized that by using the organ-on-a-chip technology we would be able to recapitulate physiology, functionality and the biomechanical cues of the native urethra and its surrounding vascular bed. Our approach consisted in using the F300R microfluidic device in combination with a rocking system to develop a potential urethra-on-a-chip. Urethral epithelial cells were used to mimic the native urethral epithelium. Gelatin-based hydrogels were tested for vasculogenic properties by placing the gel on the chick chorioallantoic membrane (CAM). Furthermore, the same gels were used for the formation of a micro vascular bed. Microvessel-like structures were formed in the gelatin-based hydrogels. Furthermore, these gels supported penetration, survival and proliferation of chicken endothelial cells when placed on the CAM. While we could only recapitulate a low fluidic shear stress (FSS) of 0.049 dyne/cm2, this was enough to form a confluent monolayer during dynamic conditions. This was not accomplished during static conditions. This project holds promise in mimicking the native layers of the urethra: epithelium and surrounding vascular tissue, under dynamic conditions. This new approach could provide a valuable platform to study the pathogenesis of urethral diseases and verify the effectiveness of drug treatment.