A novel vascularized urethra-on-a-chip model.

Area of Science:

• Biomedical Engineering
• Urology
• Regenerative Medicine

Background:

• Urethral stricture disease significantly impacts quality of life, hindering normal voiding and ejaculation.
• Molecular research for urethral diseases is limited by the absence of reliable human urethra models.
• Organ-on-a-chip technology offers potential for creating physiologically relevant in vitro models.

Purpose of the Study:

• To develop an in vitro model system of the human urethra using organ-on-a-chip technology.
• To recapitulate the physiology, functionality, and biomechanical cues of the native urethra and its vascular bed.
• To establish a platform for studying urethral diseases and evaluating drug treatments.

Main Methods:

• Utilized the F300R microfluidic device with a rocking system to create a urethra-on-a-chip model.
• Employed urethral epithelial cells to mimic the native urethral epithelium.
• Tested gelatin-based hydrogels for vasculogenic properties and microvascular bed formation on the chick chorioallantoic membrane (CAM).

Main Results:

• Successfully formed microvessel-like structures in gelatin-based hydrogels.
• Demonstrated support for chicken endothelial cell penetration, survival, and proliferation on the CAM.
• Achieved a confluent epithelial monolayer under dynamic conditions with low fluidic shear stress (0.049 dyne/cm²), which was not possible under static conditions.

Conclusions:

• The developed urethra-on-a-chip model shows promise in mimicking native urethral layers (epithelium and vascular tissue) under dynamic conditions.
• This novel in vitro platform can advance the study of urethral disease pathogenesis.
• The model provides a valuable tool for verifying the efficacy of drug treatments for urethral conditions.