A novel paradigm for the experimental characterisation and mechanical description of smooth muscle adaptivity

膀胱和胃是器官壁上含有平滑肌组织的例子。平滑肌与传统的工程材料有很大的不同，它使器官能够发挥功能，而不受其填充水平和当前形状的影响。从力学的角度来看，这种与几何无关的行为是由一种通常被称为肌肉适应性的特性所介导的。平滑肌的适应是指一个组织尺度的过程，通过这个过程，可以施加的主动力被最大化，同时最小化组织内存在的被动力。通常，平滑肌通过所谓的预处理方案进行实验研究，并以这种方式将组织减少为具有可复制力-应变行为的非弹性工程材料。与此同时，适应能力也被禁用，尽管它是控制组织在体内运作的核心特性。因此，从现有模型中获得的预测是基于涉及预处理组织样本的测量而校准的，与生理行为严重偏离，并且在增强我们对组织特异性负荷控制机制和器官自然运作的理解方面存在非常有限的范围。在这个项目中，我们提出了一种新的范例，用于实验表征平滑肌组织，同时绕过预处理。确定组织样品的生理力-应变响应的主要思路是诱导适应阶段并评估其对组织力学性能的影响。在这里，适应阶段包含特定的长时间激活协议的应用。根据我们的假设，这一过程不仅提供了对刺激诱导的适应过程和伴随的材料行为变化的见解，而且还允许对适应速率和伴随的应变松弛进行定量推断。提出的实验方法是由一个连续体力学模型的发展补充的，该模型重新审视了应变的概念，并通过延迟元件将当前的平衡构型与非应变参考构型联系起来。除了模型校准外，我们还揭示了器官壁结构特性的影响，特别是胶原与平滑肌细胞的体积比以及肌纤维取向分布。最后，该模型与描述相邻结缔组织的现有物质定律相结合，针对器官壁的综合表示，并基于完整膀胱的压力-体积测量进行验证。

The urinary bladder and the stomach are examples of organs whose walls contain smooth muscle tissue. Smooth muscles are very different from traditional engineering materials and enable the organs to function irrespective of their fill-level and current shape. From a mechanical perspective, this geometry-independent behaviour is mediated by a property which is often termed muscle adaptivity. The adaptation of smooth muscles refers to a tissue-scale process by which the active force that can be exerted is maximised, while minimising the passive force present within the tissue. Frequently, smooth muscles are experimentally investigated by applying a so-called preconditioning protocol and, in this way, reducing the tissue to an inelastic engineering material that features a reproducible force-strain behaviour. Concomitantly, the capacity for adaptation is deactivated, although it is a central property controlling the tissue's operation in vivo. As a consequence, predictions obtained from existing models which were calibrated based on measurements involving preconditioned tissue samples deviate strongly from the physiological behaviour and present very limited scope for enhancing our understanding of the tissue-specific load control mechanisms and the organ's natural operation. In this project, we propose a novel paradigm for experimentally characterising smooth muscle tissue, while circumventing preconditioning. The main idea for determining the physiological force-strain-response of tissue samples is to induce an adaptation phase and evaluating its influence on the mechanical properties of the tissue. Here, the adaptation phase encompasses the application of a specific long-time activation protocol. According to our hypothesis, this procedure not only provides insights into the stimulation-induced progress of adaptation and the concomitant changes in the material behaviour, but also allows for a quantitative inference of the adaptation rate and the accompanying strain relaxation. The proposed experimental approach is complemented by the development of a continuum mechanical model in which the notion of strain is revisited and the current equilibrium configuration is linked to the unstrained reference configuration via a delay element. Besides the model calibration, we expose the influence of structural properties of organ walls, particularly the volume ratio of collagen and smooth muscle cells as well as the muscle fibre orientation distribution. Finally, the model is combined with existing material laws describing the adjacent connective tissue, targeting an integrated representation of the organ wall, and validated based on pressure-volume measurements taken on intact urinary bladders.