Development of biomechanical models incorporating microstructures for vascular tissue rupture and implant design optimization

血管组织破裂是许多灾难性心血管疾病的常见现象，包括冠状动脉斑块破裂、主动脉夹层破裂和主动脉瘤破裂。已经提出了基于峰值应力的生物力学标准来评估疾病的严重性和破裂的可能性。然而，这些指数不能解释所有观察到的破裂。例如，对于冠状动脉斑块破裂，预测斑块肩部应力集中的传统负荷分析不能解释发生在斑块中部的大约30%的破裂。事实上，峰值应力在文献中占据主导地位，以至于某些结果基本上已经成为范例(斑块肩部破裂)。事实上，人们对血管组织破裂的生物力学还不完全了解。需要一种更好的模型来解释各种临床观察到的破裂。一个核心假设是，韧性(抗撕裂)是管理血管组织破裂的主要物理标准，病变的血管呈现微结构变化(斑块包裹物、中层变性、胶原降解)，这些缺陷构成可导致裂缝扩展的缺陷，从而导致破裂。建议使用NSERC RTI获得的新型微压头直接测量斑块微观结构(纤维帽、夹杂物)和主动脉组织壁改变(内侧退变)的固有力学性质。类似于持久S-N曲线，提出了韧性耗竭J-N曲线。实验J-N曲线的形状可以用指数型函数来拟合，并允许外推达到组织将断裂的某一韧性阈值所需的循环次数。据申请人所知，韧性耗竭的概念尚未应用于血管组织。最后，韧性的概念将被用来确定与有时由植入物引起的伤害相关的情况。事实上，血管植入物与血管组织相互作用，原因不明可能会导致损伤。这将构成第一个结合微结构和组织中尺度(细胞聚集)的设计方法。

Vascular tissue rupture is a common phenomenon associated with many catastrophic cardiovascular diseases including coronary plaque rupture, aortic dissection and aortic aneurysm rupture. Biomechanical criteria based on peak stress have been proposed to assess the severity of the diseases and the potential of rupture. However, these indexes cannot account for all observed ruptures. For example, for coronary plaque rupture, the conventional load analysis which predicts stress concentration at the plaque shoulders cannot account for about 30 % of the ruptures occurring in the mid portion of the plaque. In fact, peak stress predominates so much the literature that certain results have essentially become paradigms (rupture at plaque shoulders). The fact is that the biomechanics of vascular tissue rupture is incompletely understood. There is a need for a better model capable of explaining the various clinically observed ruptures. A core hypothesis is that toughness (resistance to tear) is the principal physical criterion governing vascular tissue rupture and that diseased vessels present microstructure alterations (plaque inclusions, medial degeneration, collagen degradation) that constitute flaws that can induce a crack propagation causing rupture. It is proposed to use the new micro-indenter just obtained with a NSERC RTI to directly measure the inherent mechanical properties of the plaque microstructures (fibrous cap, inclusions) and aortic tissue wall alterations (medial degeneration). In analogy with endurance S-N curve, a toughness exhaustion J-N curve is proposed. The shape of the experimental J-N curves can be fitted with functions of exponential type and allows for extrapolating the number of cycles required to reach a certain threshold of toughness at which the tissue would rupture. To the best of the applicant's knowledge, the concept of toughness exhaustion has not been applied to vascular tissue. Finally, the toughness concept will be used to identify the conditions associated with injuries sometimes caused by implants. Indeed, vascular implants interact with the vascular tissue and for unclear reasons can induce injuries. This would constitute the first design methodology incorporating the microstructure and the tissue mesoscale (cells agglomeration).