Biomechanics of Damage, Growth and Remodelling

损伤、生长和重塑的生物力学

• 批准号: RGPIN-2015-06027
• 负责人: Federico, Salvatore
• 金额: $ 4.23万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=759758
• 关键词: Biomechanics; Damage; Growth; Remodelling

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.

生物组织构成生物的器官，由嵌入在称为细胞外基质的地面材料中的相同类型的细胞组成。细胞外基质可以描述为多孔材料，被胶原蛋白纤维增强，并被溶解几种化学物质的液体饱和。工程材料和生物组织之间的最大区别在于，后者是与周围环境相互作用并感知刺激的生物。由于这些相互作用，它们会经历增长，重塑过程，在不幸的情况下是伤害和损害。生长被定义为质量的增加（积聚）或减少（吸收），重塑为内部结构的重排，而损害是结构完整性的丧失。我们的研究旨在开发一种统一的生物组织的连续机械模型，以构成损害，生长和重塑以及三种现象之间的相互作用。我们寻求一个基于能量的模型，即，几乎所有有关组织行为的信息都可以包含在单个数学函数中，即（Helmholtz）自由能。自由能的数学表达的推导来自于组织的微观结构的考虑。具体而言，我们对基质中的大分子，外部刺激下的胶原蛋白纤维的重新定位感兴趣，这是重塑的很大一部分和胶原纤维衰竭，最终决定了组织损伤。将重点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成部分。类似于以前从未尝试过的一般方法，并将为我们提供有关这些现象中复杂相互作用的信息，否则这实际上是不可能量化实验的。具体的实验将在简单的几何形状上进行，以验证模型的损害和重塑方面。该研究的长期目标是：1）模拟软组织中损害的分子损伤的分子机制，以及损害触发和与生长的触发和相互作用如何与生长和重塑相互作用；促进特定的反应，以及能够替代不可避免地损坏组织的组织工程材料，就像关节软骨一样。该计划将在连续力学的基础上及其在软组织生物力学以及模型验证所需的实验技术中的基础上的研究生和博士后的培训。