Multiscale simulation and measurement of knee joints biomechanics under physiological loading conditions

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The direct economic burden of knee articular cartilage (AC) failure is $10 billion and is expected to grow over the next decade. Mechanical stimuli, such as stresses and strains, induced by physical activities, are a regulator of AC homeostasis. However, clinicians and researchers still do not know what type and level of mechanical loads are safe and effective to reduce the risk of AC degeneration. The proposed research program will address two primary limitations in this field, with broad applications for studying soft tissue mechanics in general. First, we do not have adequate tools to measure and predict how physical activities at the joint level deform AC chondrocytes at the cellular level. Much of the information currently available on chondrocyte mechanics were obtained from experiments on chondrocytes in embedded gel under static loads, which provides a controlled mechanical and biochemical environment. In the proposed research, we will develop an experimental apparatus and employ novel microscopy techniques to measure the local deformations of chondrocyte and extracellular matrix (ECM) at different zones in native AC under dynamic loading conditions. We will study the level of joint forces that promote cell biosynthesis, beginning with simple cyclic loadings and culminating in physiological loading conditions. Moreover, we will study the microscale deformations of ECM near a microscale crack in AC, to elucidate the mechanism of crack propagation in ECM. Second, we lack a biologically informed finite element (FE) model of the full knee joint that includes the chondrocyte response in the joint function. Traditional knee FE models are purely mechanical and study the acute response of AC to mechanical disturbances, such as injuries. However, cartilage failure is a chronic condition that involves tissue degeneration and cracks propagation over time. This proposal aims at developing a fiber-reinforced cartilage model and applies it into a full 3D knee FE model that includes muscles and bones (tissue level) as well as chondrocytes (cellular level). The novelty of the proposed multiscale knee FE model lies in the unique approach in linking the tissue-scale cartilage deformations to the cellular-scale chondrocyte bioactivity that accounts for the rate of cartilage growth. Such a biologically informed multiscale FE model would identify the long-term effects of applied loads on the AC function. The expected outcome of this work is to outline pathways to establish confidence in identifying physical activities that promote favorable conditions for chondrocyte function and cartilage production in cartilage. This offers a number of benefits to the society (prevented joint injuries) as well as the economy (reduced burden costs of knee joint failure treatments). In addition to technical advancements, my research group trains at least 9 HQP who help meet Canada's demand for engineers and will contribute to its economic success.