Biomechanics of Damage, Growth and Remodelling

生物组织构成生物的器官，由嵌入在称为细胞外基质的基质中的相同类型的细胞组成。细胞外基质可以被描述为一种多孔材料，由胶原纤维增强，并被一种溶解了几种化学物质的液体饱和。工程材料和生物组织最大的区别是后者是与周围环境相互作用并感受到来自周围环境的刺激的活材料。由于这些相互作用，它们经历了生长、改造的过程，在不幸的情况下，还会造成伤害和破坏。生长被定义为质量的增加(增加)或减少(再吸收)，重塑被定义为内部结构的重新排列，而损伤被定义为结构完整性的丧失。我们的研究旨在建立一个统一的生物组织损伤、生长和重塑的连续统力学模型，以及这三种现象之间的相互作用。我们寻求一种基于能量的模型，即一种模型，在该模型中，关于组织行为的几乎所有信息都可以包含在单个数学函数中，即(亥姆霍兹)自由能。自由能数学表达式的推导源于对组织微观结构的考虑。具体地说，我们感兴趣的是基质中大分子之间的机电相互作用，在外部刺激下胶原纤维重新定向，这是重塑的很大部分，以及胶原纤维失效，最终决定组织损伤。重点将放在血管和关节软骨的研究上，并将进行实验以验证统一模型的各个组件。这种一般方法以前从未尝试过，它将使我们有可能获得关于这些现象之间复杂相互作用的信息，否则几乎不可能在实验中量化。这项研究的长期目标是：1)模拟软组织损伤的分子机制，以及损伤如何触发生长和重建并与其相互作用；2)设计旨在通过机械、化学、电刺激组织中细胞的生物合成反应以促进特定反应的技术，以及能够取代不可修复的受损组织的组织工程材料，就像关节软骨的情况一样。该方案将大力促进研究生和博士后在连续统力学基础及其在软组织生物力学中的应用，以及模型验证所需的实验技术方面的培训。

Biological tissues constitute the organs of living beings, and are comprised of cells of the same type embedded in a ground material called extracellular matrix. The extracellular matrix can be described as a porous material, reinforced by collagen fibres and saturated by a fluid in which several chemical substances are dissolved. The greatest difference between engineering materials and biological tissues is that the latter are living materials that interact with and sense stimuli from the surrounding environment. Because of these interactions, they undergo processes of growth, remodelling and, in unfortunate cases, injury and damage. Growth is defined as the increase (accretion) or decrease (resorption) of mass, remodelling as the rearrangement of the internal structure, and damage as the loss of structural integrity. Our research is aimed at developing a unified continuum mechanical model of biological tissues accounting for damage, growth and remodelling, as well as for the interaction among the three phenomena. We seek for an energy-based model, i.e., a model in which virtually all information about the behaviour of the tissue can be included in a single mathematical function, the (Helmholtz) free energy. The derivation of the mathematical expression of the free energy comes from considerations made on the microstructure of the tissue. Specifically, we are interested in the electromechanical interactions among the macromolecules in the matrix, collagen fibre reorientation under external stimuli, which accounts for a good part of the remodelling, and collagen fibre failure, which ultimately determines tissue damage. Emphasis will be placed on the study of blood vessels and articular cartilage, and experiments will be performed to validate the individual components of the unified model.Such a general approach has never been attempted before and will give us the possibility to obtain information on the complex interaction among these phenomena, which is otherwise virtually impossible to quantify experimentally. Specific experiments will be performed on simple geometries to validate the damage and remodelling aspects of the model, individually.The long-term objectives of this research are: 1) To model the molecular mechanisms of damage in soft tissues, and how damage triggers and interacts with growth and remodelling;2) To design techniques aimed at mechanically, chemically, electrically stimulating the biosynthetic response of the cells in the tissue in order to promote a specific response, as well as tissue-engineered materials capable of replacing irremediably damaged tissue, as is the case for articular cartilage. This programme will strongly contribute to the training of graduate students and postdocs in the foundations of Continuum Mechanics and its applications to Soft Tissue Biomechanics, as well as in the experimental techniques necessary for model validation.