Mathematical Modeling of Bladder Mechanobiology

Lower urinary tract symptoms (LUTS), including an increase of urination urgency, frequency, incontinence, residual volume, are relevant to the deterioration of bladder mechanical function and can significantly lower the quality of life. Urodynamics, the gold standard of bladder diagnosis, has often been used to assess bladder functionality. Urodynamic data, which include pressure and volume change during filling, are affected by the mechanical properties of the bladder. However, the underlying mechanisms of bladder pathologies are not fully understood and therefore the interpretation of urodynamic data is highly subjective and may be inconclusive; often requiring further testing or leading to inappropriate treatment. Although morphological changes such as smooth muscle hypertrophy and collagen fibrosis have been commonly observed in the dysfunctional bladder, the effect of these changes on the bladder mechanical function has not been fully explained. In this work, we integrated in situ mechanical testing and multiphoton microscopy to assess bladder mechanical properties and reorganization, growth and remodeling. As a first step, a constitutive model, motivated by the collagen fiber structure, was developed and used to investigate the mechanical function under aging, disease, and pharmacological treatments. This model was then further sophisticated to model the bladder filling and voiding process by integrating the results from in-vivo and ex-vivo experiments. Lastly, a growth and remodeling framework, which has demonstrated its success in many other soft tissues (artery, heart, etc.), was modified and used to simulate the adaptive remodeling within the bladder wall driven by bladder outlet obstruction. Our long-range objective is to improve patient care and develop novel treatments. This present work provides insights on mechanisms of bladder function and remodeling that lay the necessary foundation for the next steps toward this goal