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

膀胱是脊椎动物的中枢器官。其主要功能是储存大量的尿液，这意味着非常大的变形，这导致了膀胱力学的重要作用。特别是由机械刺激控制的生长和重塑过程在健康和疾病中起着重要作用。例如，膀胱的部分出口梗阻-50岁以上的男性人群中有50%至75%患有膀胱部分出口梗阻-经常导致病理性生长和重塑，其后果例如是尿缺血。然而，机械调节的膀胱生长和重塑的生物力学基础至今仍知之甚少。该项目旨在了解和量化膀胱中机械调节的生长和重塑过程。为此，将对不同年龄的青春期后猪膀胱进行一系列生物力学和免疫组织化学实验。这些实验的结果将作为膀胱中机械调节的生长和重塑的世界范围内第一个数学/计算模型的发展的基础。为了排除激素的混杂效应，将测量其浓度并适当纳入模型中。数学模型将基于约束混合物理论。其参数和函数关系将使用顺序蒙特-卡罗方法从实验数据确定。最后，该模型将用于研究第一次与一个非常简单的计算模型机械调节的生长和重建的情况下，部分出口梗阻的膀胱。通过这种方式，将证明本项目结果对临床相关问题的适用性。虽然该项目主要关注机械刺激与生长和重塑之间的关系，但作为副产品，它也将首次揭示激素和机械因素如何共同控制膀胱的生长和重塑。在这个项目中开发的模型的一个特别的优势将是其强大的和定量的数据基础，注意到，大多数机械调节的软组织生长和重塑的数学/计算模型，到目前为止，仍然受到实验基础不足。

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.