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

青春期后猪膀胱机械调节生长和重塑过程的实验分析和数学建模

• 批准号: 386349077
• 负责人: Professor Dr.-Ing. Markus Böl
• 金额: --
• 依托单位: Institut für Kontinuums- und Werkstoffmechanik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/386349077?language=en
• 关键词: Experimental; analysis; mathematical; modelling; mechano

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.

膀胱是脊椎动物的中心器官。它的主要功能是储存大量尿液，这意味着非常大的变形，这导致膀胱力学发挥重要作用。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发挥着重要作用。例如，50 岁以上男性人群中有 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，并产生缺血等后果。然而，迄今为止，人们对膀胱机械调节生长和重塑的生物力学基础仍然知之甚少。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的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开发世界上第一个膀胱机械调节生长和重塑的数学/计算模型的基础。为了排除激素的混杂影响，将测量激素的浓度并将其适当地纳入模型中。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根据实验数据确定。最后，该模型将首次用于研究非常简单的计算模型机械调节生长和重塑，以防膀胱部分出口梗阻。通过这种方式，将证明该项目的结果对临床相关问题的适用性。尽管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叠加控制膀胱的生长和重塑。该项目开发的模型的一个特殊优势是其强大的定量数据基础，注意到迄今为止软组织中机械调节生长和重塑的大多数数学/计算模型仍然存在实验基础不足的问题。