Multiscale three dimensional modelling of articular cartilage

骨关节炎(OA)影响着400多万加拿大人，并会导致剧烈疼痛和限制活动。开放式获取的直接和间接费用总额为每年64亿美元。由于人口老龄化，到2031年，受OA影响的患者数量预计将上升到670万人，给经济和医疗体系带来进一步的负担。骨性关节炎的特征是关节软骨的损伤和丢失，以及关节表面正下方的骨密度增加。在其他因素中，骨性关节炎是由于软骨组织的机械负荷过重造成的。患者的活动，即关节运动和负荷、关节几何形状和组织衰竭之间的关系还不是很清楚。先进的计算机模拟模型可以用来检查小软骨样本的力学行为，但由于计算要求过高，不能用于关节的真实模型。因此，这项研究的目标是1)开发和验证可用于宏观尺度的简化软骨材料模型；以及2)开发多尺度计算机模型，以评估宏观组织变形如何影响微观水平的应力，从而解释与进展性骨关节炎相关的软骨组织失效。这项研究将把对软骨样本的测试与计算机模拟结合起来。实验数据将被用来证实计算机模拟在从正常日常活动到创伤损伤的不同负荷率下预测的粗略行为。将开发新的多尺度模拟技术用于计算机模拟，以了解软骨组织变形是如何通过分子网络和流体传递的，这些分子和流体可能会对分子造成破坏或改变细胞的力学环境。这些技术将有助于研究患者特定关节模型中的实际损伤，以及识别因常见关节畸形而有退变风险的患者。这项研究中开发的技术的进一步应用是在组织工程软骨的开发中优化实验室加载方案，以替换严重退化的天然软骨。

Osteoarthritis (OA) affects over 4 million Canadians and can cause severe pain and limit activities. Total of direct and indirect costs of OA are $6.4 billion per year. Due to an aging population, the number of patients affected by OA is expected to rise to 6.7 million by 2031, imposing further burdens on the economy and healthcare system. OA is characterized by damage and loss of articular cartilage as well as increased bone density immediately below the joint surface. Among other factors, OA results from mechanical overload of the cartilage tissue. The relationship between patient activities, i.e. joint motions and loading, joint geometry and tissue failure is not well understood. Advanced computer simulation models may be used to examine mechanical behaviour of small cartilage specimens, but cannot be used in realistic models of the joint due to excessive computational requirements. The goal of this study is therefore 1) to develop and validate simplified material models of cartilage that may be used at the macroscopic scale; and 2) to develop multi-scale computer models to assess how the macroscopic tissue deformations influence stresses at the microscopic level that may explain cartilage tissue failure associated with advanced OA. The study will combine testing of cartilage samples with computer simulation. Experimental data will be used to confirm the gross behaviour predicted by computer simulations under loading rates varying from normal daily activities to traumatic injury. Novel multi-scale modelling techniques will be developed for the computer simulations to understand how cartilage tissue deformations are transmitted through the molecular network and fluid that may cause damage to the molecules or alter the mechanical environment of cells. These techniques will be useful to study actual damage in patient-specific models of articular joints as well as to identify patients at risk of degeneration due to common joint deformities. A further use of the techniques developed in this study is to optimize laboratory loading protocols in the development of tissue-engineered cartilage for replacement of severely degenerated native cartilage.