Active, three-dimensional stomach deformation - experiment and simulation

胃是脊椎动物的中枢器官，由于它的极端变形，对胃组织，特别是对活跃的平滑肌提出了特殊的要求。虽然各种功能障碍和相关的组织变化是已知的，但与其他器官相比，力学研究很少。因此，该提案的主要目标是开发和验证猪胃模型。在项目的第一阶段，可以收集到局部和层特异性胃结构和机械组织特性的高分辨率数据集，并在此基础上开发了电化学力学胃模型。为了完成模型开发，特别是模型验证，各种实验和基于模型的任务仍然是必要的，这些任务在第一个项目阶段出现，并将在当前后续应用的背景下进行。意想不到的问题出现了，例如，在刺激胃窦时，这是有趣的，一方面，因为这表明胃区域之间存在显着的电化学力学差异，另一方面，这导致了项目计划过程的延迟，并且有必要开发其他方法。测量将在剥皮的、分离的鼻窦平滑肌纤维束上进行，以确定鼻窦的机械性能。为了在组织条水平上验证胃模型，我们将首次进行主动双轴实验。此外，现实的模型预测需要通过免疫组织学调查来确定这些组织条的微观结构和组成。此外，还将进行验证全胃模型所需的全胃主动实验，测量全胃变形和产生的内压。在第一个项目阶段确定的肌肉力的明显的历史依赖性（力下降，力增强）需要一个模型扩展来预测实际的内部胃压力和变形。在项目的最后阶段，一步一步的模型验证将在测量的三维变形和力/压力上进行，首先在组织条水平上，最后在整个器官水平上。建立的胃模型是对动物实验的一种替代和补充方法，基于人胃和猪胃的相似性，可以用于人体研究。因此，它可以有助于减少动物实验，并在未来更好地了解胃的功能。

The stomach is a central organ of vertebrates and, due to its extreme deformations, places special demands on the stomach tissue and especially on the active smooth muscle. Although a variety of dysfunctions and associated tissue changes are known, mechanical studies are scarce compared to other organs. Thus, the main objective of the proposal is to develop and validate a porcine stomach model. In the first phase of the project, it was possible to collect a high-resolution data set on the local and layer-specific stomach structure and the mechanical tissue properties, on the basis of which an electro-chemomechanical stomach model was developed. For the completion of the model development and in particular the model validation, various experimental and model-based tasks are still necessary, which arose in the first project phase and are to be worked on in the context of the present follow-up application. Unexpected problems arose, e.g., in the stimulation of the antrum, which is interesting on the one hand, as this indicates significant electro-chemomechanical differences between the gastric regions, on the other hand, this led to delays in the planned course of the project and makes it necessary to develop other approaches. Measurements are to be carried out on skinned, isolated smooth muscle fibre bundles of the antrum in order to determine the mechanical properties of the antrum. For a validation of the stomach model on tissue strip level, active biaxial experiments are to be carried out for the first time. Furthermore, realistic model predictions require the determination of the microstructure and composition of these tissue strips by means of immunohistological investigations. In addition, the active experiments on the whole stomach necessary for validating the whole stomach model will be carried out by measuring the whole stomach deformation and the generated internal pressures. The pronounced history dependence (force depression, force enhancement) of muscle force determined in the first project phase requires a model extension to predict realistic internal stomach pressures and deformations. In the final project phase, a step-by-step model validation is to take place on the measured three-dimensional deformations and forces/pressures, first at tissue strip level and finally at whole organ level. The developed stomach model represents a substitute and complementary method to animal experiments and, based on the similarity of the human and pig stomach, to human studies. It can thus contribute to the reduction of animal experiments and to a better understanding of stomach function in the future.