Development and validation of a three-dimensional electro-chemo-mechanical model for the discription of the urinary bladder

膀胱是脊椎动物的中心器官，并且基于其极端变形（体积变化高达几个100%），对整个膀胱组织，特别是对活性平滑肌组织提出了特殊要求。虽然有许多功能障碍与组织变化相结合，机械分析是罕见的。因此，本课题的主要目的是在猪膀胱实验研究的基础上建立一个电化学力学模型，并对其进行验证。因此，将对家猪进行实验，因为结构和收缩行为与人类相似。模型生成的基本要求是所用技术的发展（I）。这些是三维变形以及膀胱表面处的激活电位传播的配准。基于申请人开发的用于记录骨骼肌变形的光学测量技术，在本项目中，将建立一种程序来测量生理盐水溶液中的膀胱几何形状。此外，将开发用于测量膀胱表面处的动作电位的传播的表面电极。第一个实验步骤包括分析组织条（II）。为了捕获膀胱结构的局部差异，将在膀胱壁的限定位置处解剖制备物。因此，可以确定特定于层的架构及其有源和无源特性。这些数据用于临时验证和电化学机械模型的参数识别。基于对整个膀胱（III）的主动和被动分析，将确定其容量、压力-体积依赖性、三维变形和膀胱表面的动作电位的传播。在最后一步中，使用整个膀胱的这些附加数据来验证整个模型（IV）。在该项目中开发的模型可以被看作是用于动物模型的补偿方法，并且基于人类和猪膀胱之间的相似性，用于人类研究。因此，它可以有助于在未来减少动物实验，并可以帮助有一个更全面的了解膀胱功能。该模型的前瞻性发展可以处理组织变化的不同功能影响的预测（即，由于间质性膀胱炎引起的肌肉层瘢痕化）。因此，患病组织的形态和机械变化将通过实验确定，并实施和转换成模型。

The urinary bladder is a central organ of vertebrates and imposes, based on its extreme deformation (volume changes up to several 100%), special requirements on the entire bladder tissue and especially on the active smooth muscle tissue. Although there are many dysfunctions combined with tissue changes, mechanical analyses are rare. Consequently, the main aim of this project is the development and validation of an electro-chemo-mechanical model based on experimental investigations on the swine urinary bladder.For the development and validation of the model, four steps are scheduled. Thereby, experiments on domestic pigs will be performed, as structure and contraction behaviour are similar to those of humans. Basic requirement for the model generation is the development of the used techniques (I). These are the registration of the three-dimensional deformation as well as of the activation potential propagation at the bladder's surface. Based on an optical measurement technique, developed by the applicants for the recording of skeletal muscles deformation, in this project a procedure will be established to measure the bladder geometry in physiological saline solution. Further, surface electrodes for the measurement of the propagation of the action potential at the bladder's surface will be developed. The first experimental step includes analyses of tissue strips (II). In order to capture local differences of the bladder's structure, preparations will be dissected at defined positions of the bladder wall. Thus, the layer specific architecture as well as its active and passive characteristics can be determined. These data are used for an interim validation and the parameter identification of the electro-chemo-mechanical model. Based on active and passive analyses on the whole bladder (III) its capacity, the pressure-volume dependence, the three-dimensional deformation and the propagation of the action potential at the bladder's surface will be determined. In a final step these additional data of the whole bladder are used to validate the whole model (IV).The model developed in this project can be seen to be a compensational method for animal models and, based on the similarity between human and porcine bladders, for human studies. Thus, it can contribute in future to a reduction of animal experiments and can help to have a more comprehensive understanding of bladder functions. Prospective developments of the model could deal with the prediction of different functional impacts of tissue changes (i.e. cicatrisation of the muscle layer due to interstitial cystitis). Therefore, morphological and mechanical changes of the sickened tissue will be determined experimentally and implemented and converted into the model.