Mutliscale Mechanics, Mechanobiology and Imaging of Musculoskeletal Tissues

肌肉骨骼组织的多尺度力学、力学生物学和成像

• 批准号: RGPIN-2017-04841
• 负责人: Duncan, Neil
• 金额: $ 1.6万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=678808
• 关键词: Mutliscale; Mechanics; Mechanobiology; Imaging; Musculoskeletal

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.

肌肉骨骼系统的功能主要是使运动和传递机械负荷，但也有生物组织的能力，以维持和修复自己在整个生命。退行性椎间盘疾病、骨关节炎、骨质疏松症和重复负荷综合征是西方世界最常见的发病原因，随着人口老龄化，这些疾病的患病率可能会增加。机械因素，如重复性举重任务和急性超负荷，长期以来一直与肌肉骨骼疾病的病因有关。结缔组织如椎间盘、关节软骨和肌腱在生物学、生物化学和生物力学上随着衰老、退化和损伤而在多个尺度上改变。为了了解机械，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，以将日常任务中的组织水平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。 对多尺度力学和机械生物学的更深入理解对于开发更好的诊断工具和合理设计骨科疾病的组织工程治疗至关重要，如退行性椎间盘疾病，损伤的肌腱和韧带，退行性骨折和骨关节炎。组织工程为干细胞种植生物材料支架治疗退行性肌肉骨骼疾病提供了巨大的潜力。然而，为了开发功能性组织工程构建体，控制干细胞分化为组织的因素需要更好地理解细胞-基质相互作用。为了使组织工程治疗最有效，需要更多的定量诊断，以便在疾病进展的较早时间点治疗受损较少的组织，从而避免或至少延迟目前实践中对全关节置换和融合的更具侵入性治疗的需要。因此，该研究计划由三个具有长期目标的项目驱动：I）调查和量化结缔组织的多尺度力学，II）调查和了解组织工程治疗的3-D支架中干细胞分化的机械生物学，以及III）开发和应用定量诊断成像来表征肌肉骨骼组织的功能完整性。总之，这些新知识对于推进肌肉骨骼疾病的治疗和诊断至关重要，如退行性椎间盘疾病，骨关节炎和骨质疏松症，这些疾病损害了加拿大老年人的流动性，并可能极大地影响生活质量和整体健康。