Multiscale three dimensional modelling of articular cartilage

骨关节炎（OA）影响超过400万加拿大人，可导致严重疼痛和限制活动。有机农业的直接和间接成本每年为64亿美元。由于人口老龄化，到2031年，受OA影响的患者人数预计将增加到670万，这将给经济和医疗保健系统带来进一步的负担。OA的特征在于关节软骨的损伤和损失以及关节表面正下方的骨密度增加。在其他因素中，OA由软骨组织的机械过载引起。患者活动（即关节运动和载荷）、关节几何形状和组织失效之间的关系尚不清楚。先进的计算机模拟模型可用于检查小软骨标本的机械性能，但由于计算要求过高，不能用于关节的真实模型。因此，本研究的目标是1）开发和验证可用于宏观尺度的软骨简化材料模型; 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，这可能解释与晚期OA相关的软骨组织失效。这项研究将结合联合收割机测试软骨样品与计算机模拟。实验数据将用于确认在从正常日常活动到创伤性损伤的载荷率变化下通过计算机模拟预测的总体行为。新的多尺度建模技术将被开发用于计算机模拟，以了解软骨组织变形如何通过分子网络和流体传递，这可能会导致分子损伤或改变细胞的机械环境。这些技术将有助于研究患者特定关节模型的实际损伤，以及识别因常见关节畸形而有退化风险的患者。在这项研究中开发的技术的进一步使用是优化实验室加载协议的组织工程软骨的发展，以取代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.