Mutliscale Mechanics, Mechanobiology and Imaging of Musculoskeletal Tissues

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The musculoskeletal system functions primarily to enable mobility and transmit mechanical loads, yet also has the ability of biological tissues to maintain and repair itself throughout life. Degenerative disc disease, osteoarthritis, osteoporosis, and repetitive loading syndromes are some of the most prevalent causes of morbidity in the Western world, which will likely increase in prevalence with an aging population. Mechanical factors, such as repetitive lifting tasks and acute overloading, have long been implicated in the etiology of musculoskeletal disorders. Connective tissues such as intervertebral disc, articular cartilage and tendon are altered at multiple scales biologically, biochemically and biomechanically with ageing, degeneration and injury. To understand the role of mechanical, biological and genetic factors in musculoskeletal disorders requires the detailed knowledge of how the cells interact in situ with the extracellular matrix (ECM) to transduce tissue level mechanical factors in daily tasks into biological signals within the cells. Mechanobiology studies clearly show that mechanical factors can influence the biosynthetic activity of cells, altering the expression of key ECM genes. A greater understanding of multiscale mechanics and mechanobiology is essential to develop better diagnostic tools and to rationally design tissue engineered treatments for orthopaedic disorders such as degenerative disc disease, injured tendons and ligaments, osteoporotic fractures and osteoarthritis.***Tissue engineering offers great potential to treat degenerative musculoskeletal disorders with stem cell seeded biomaterial scaffolds. However, to develop functional tissue engineered constructs, the factors controlling differentiation of stem cells into tissues requires a greater understanding of cell-matrix interactions. For tissue engineered treatments to be most effective, more quantitative diagnostics are needed so that less damaged tissues can be treated at an earlier time point in the disease progression, and thereby avoid, or at least delay, the need for more invasive treatments of total joint replacements and fusions in current practice.***Therefore, the research program is driven by three projects with long-term objectives: I) to investigate and quantify the multiscale mechanics of connective tissues, II) to investigate and understand the mechanobiology of stem cell differentiation in 3-D scaffolds for tissue engineering treatments, and III) to develop and apply quantitative diagnostic imaging to characterize the functional integrity of musculoskeletal tissues. Together, this new knowledge is essential to advance treatments and diagnostics for musculoskeletal disorders such as degenerative disc disease, osteoarthritis and osteoporosis which impair the mobility of ageing Canadians, and can greatly affect quality of life and overall health.