Mutliscale Mechanics, Mechanobiology and Imaging of Musculoskeletal Tissues

肌肉骨骼系统的功能主要是实现活动和传递机械负荷，但也具有生物组织在整个生命过程中维持和修复自身的能力。椎间盘退行性疾病、骨关节炎、骨质疏松症和重复性负荷综合征是西方世界最普遍的发病原因，随着人口老龄化，患病率可能会增加。机械因素，如重复性举重任务和急性超载，长期以来被认为与肌肉骨骼疾病的病因有关。结缔组织，如椎间盘、关节软骨和肌腱，随着衰老、退化和损伤，在生物学、生物化学和生物力学上发生多种尺度的改变。要了解机械、生物和遗传因素在肌肉骨骼疾病中的作用，需要详细了解细胞如何与细胞外基质（ECM）原位相互作用，将日常任务中组织水平的机械因素转化为细胞内的生物信号。机械生物学研究清楚地表明，机械因素可以影响细胞的生物合成活性，改变关键ECM基因的表达。更好地理解多尺度力学和力学生物学对于开发更好的诊断工具和合理设计组织工程治疗骨科疾病（如退行性椎间盘疾病、受伤的肌腱和韧带、骨质疏松性骨折和骨关节炎）至关重要。

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.