Multiscale three dimensional modelling of articular cartilage

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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.