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枢器官，由于其剧烈的变形（体积变化可达100%），对整个膀胱组织，尤其是活跃的平滑肌组织提出了特殊的要求。虽然有许多功能障碍合并组织改变，力学分析是罕见的。因此，本项目的主要目的是基于猪膀胱的实验研究，开发和验证电化学-力学模型。对于模型的开发和验证，计划了四个步骤。因此，将在家猪身上进行实验，因为它们的结构和收缩行为与人类相似。模型生成的基本要求是所使用的技术(1)的发展。这些是三维变形的记录以及膀胱表面的激活电位传播。基于一种光学测量技术，由申请人开发用于记录骨骼肌变形，在本项目中，将建立一个程序来测量生理盐水溶液中的膀胱几何形状。此外，用于测量动作电位在膀胱表面传播的表面电极将被开发。第一个实验步骤包括组织条的分析（II）。为了捕捉膀胱结构的局部差异，将在膀胱壁的指定位置解剖准备物。从而确定层的具体结构及其主动式和被动式特征。这些数据用于电化学-力学模型的临时验证和参数识别。通过对整个膀胱的主动和被动分析（III）其容量，确定膀胱表面的压力-体积依赖性、三维变形和动作电位的传播。在最后一步，这些额外的全膀胱数据被用来验证整个模型（IV）。在这个项目中开发的模型可以被看作是动物模型的一种补偿方法，并且基于人类和猪膀胱之间的相似性，用于人类研究。因此，它可以在未来减少动物实验，并有助于对膀胱功能有更全面的了解。该模型的未来发展可用于预测组织变化（如间质性膀胱炎引起的肌肉层瘢痕）对不同功能的影响。因此，患病组织的形态学和力学变化将通过实验确定并实现并转化为模型。

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.