Experimental analysis and mathematical modelling of mechano-regulated growth and remodelling processes in urinary bladders of post-pubescent pigs

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The urinary bladder is a central organ of vertebrates. Its primary function, the storage of significant volumes of urine, implies very large deformations, which leads to an important role of mechanics in the urinary bladder. In particular growth and remodeling processes controlled by mechanical stimuli play an important role both in health and disease. For example, partial outlet obstruction of the bladder - from which 50% to 75% of the male population older than 50 years suffer - frequently results in pathological growth and remodeling with consequences such as ischuria. However, the biomechanical foundations of mechano-regulated growth and remodeling in the bladder remain poorly understood to date. This project aims to understand and quantify mechano-regulated growth and remodelling processes in the urinary bladder. To this end, a series of biomechanical and immunohistochemical experiments with urinary bladders of post-pubescent pigs of different ages will be conducted. The results of these experiments will serve as a basis for the development of the world-wide first mathematical/computational model of mechano-regulated growth and remodeling in the urinary bladder. To exclude confounding effects of hormones, their concentrations will be measured and incorporated appropriately in the model. The mathematical model will be based on the theory of constrained mixtures. Its parameters and functional relations will be determined from the experimental data using a sequential Monte-Carlo method. Finally, the model will be used to study for the first time with a very simple computational model mechano-regulated growth and remodeling in case of a partial outlet obstruction of the urinary bladder. This way, the applicability of the results of this project to clinically relevant questions will be demonstrated. Although this project mainly focuses on the relation between mechanical stimuli and growth and remodeling, it will, as a byproduct, also reveal for the first time how hormonal and mechanical factors superimpose in controlling growth and remodeling in the urinary bladder. A particular strength of the model developed in this project will be its strong and quantitative data basis, noting that most mathematical/computational models of mechano-regulated growth and remodeling in soft tissue so far still suffer from an insufficient experimental basis.