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央器官。它的主要功能是大量尿液的储存，这意味着非常大的变形，这导致力学在膀胱中的重要作用。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，膀胱的部分出口障碍物（其中50％至75％的50岁以上男人受到损害）经常导致病理生长并重塑，并带有静脉尿液等后果。然而，迄今为止，机械调节生长和重塑的生物力学基础仍然很少理解。该项目旨在了解和量化膀胱中的机械调节的生长和重塑过程。为此，将进行一系列生物力学和免疫组织化学实验。这些实验的结果将是开发全球膀胱中机械调节生长和重塑的首次数学/计算模型的基础。为了排除激素的混杂作用，将适当地测量其浓度并在模型中融合。数学模型将基于约束混合物的理论。它的参数和功能关系将使用顺序蒙特卡洛方法从实验数据确定。最后，该模型将首次使用非常简单的计算模型机械调节的生长和重塑，以防泌尿膀胱的部分出口阻塞。这样，将证明该项目结果对临床相关问题的适用性。尽管该项目主要集中于机械刺激与生长和重塑之间的关系，但作为副产品，它也将首次揭示荷尔蒙和机械因素如何控制尿膀胱中的生长和重塑时​​如何叠加。该项目中开发的模型的特殊优势将是其强大而定量的数据基础，并指出到目前为止，机械调节的生长和重塑的大多数数学/计算模型迄今仍未遭受实验基础的不足。