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 th...

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Main Authors: Aina Casademont-Roca, Zhentao Xing, Murillo Bernardi, Maarten Rookmaker, Laetitia de Kort, Petra de Graaf
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-92485-9
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author Aina Casademont-Roca
Zhentao Xing
Murillo Bernardi
Maarten Rookmaker
Laetitia de Kort
Petra de Graaf
author_facet Aina Casademont-Roca
Zhentao Xing
Murillo Bernardi
Maarten Rookmaker
Laetitia de Kort
Petra de Graaf
author_sort Aina Casademont-Roca
collection DOAJ
description 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.
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spelling doaj-art-46ec09bce82044a2adaae259df33a1562025-08-20T03:05:52ZengNature PortfolioScientific Reports2045-23222025-03-0115111410.1038/s41598-025-92485-9A novel vascularized urethra-on-a-chip modelAina Casademont-Roca0Zhentao Xing1Murillo Bernardi2Maarten Rookmaker3Laetitia de Kort4Petra de Graaf5Department of Urology, University Medical Center UtrechtDepartment of Urology, University Medical Center UtrechtDepartment of Nephrology, University Medical Center UtrechtDepartment of Nephrology, University Medical Center UtrechtDepartment of Urology, University Medical Center UtrechtDepartment of Urology, University Medical Center UtrechtAbstract 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.https://doi.org/10.1038/s41598-025-92485-9Urethra-on-a-chipOrgan-on-a-chipDisease modelingUrethral stricture disease
spellingShingle Aina Casademont-Roca
Zhentao Xing
Murillo Bernardi
Maarten Rookmaker
Laetitia de Kort
Petra de Graaf
A novel vascularized urethra-on-a-chip model
Scientific Reports
Urethra-on-a-chip
Organ-on-a-chip
Disease modeling
Urethral stricture disease
title A novel vascularized urethra-on-a-chip model
title_full A novel vascularized urethra-on-a-chip model
title_fullStr A novel vascularized urethra-on-a-chip model
title_full_unstemmed A novel vascularized urethra-on-a-chip model
title_short A novel vascularized urethra-on-a-chip model
title_sort novel vascularized urethra on a chip model
topic Urethra-on-a-chip
Organ-on-a-chip
Disease modeling
Urethral stricture disease
url https://doi.org/10.1038/s41598-025-92485-9
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