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.

肌肉骨骼系统的作用主要是为了实现迁移率和传输机械载荷，但也具有生物组织在整个生命中保持和修复的能力。退化性椎间盘疾病，骨关节炎，骨质疏松症和重复负荷综合征是西方世界中发病率最普遍的一些原因，这可能会随着老龄化人群的流行而增加。机械因素（例如重复提升任务和急性超负荷）长期以来一直与肌肉骨骼疾病的病因有关。结缔组织，例如椎间盘，关节软骨和肌腱在生物学，生化和生物力学上以衰老，变性和损伤的方式在多个尺度上改变。要了解机械，生物学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子转换为细胞内生物学信号。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，从而改变关键ECM基因的表达。 对多阶段力学和机械生物学的更多了解对于开发更好的诊断工具和合理设计组织工程治疗的骨科疾病，例如退化性椎间盘疾病，受伤的肌腱和韧带，骨质骨质骨折和骨质关节炎。脚手架。但是，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对细胞基质相互作用有更多的了解。为了使组织工程的治疗最有效，需要更定量的诊断，以便可以在疾病进展的较早时间点进行损坏的组织，从而避免，从而避免或至少延迟需要对当前实践中的全部关节置换和融合进行更多侵入性治疗的需求。并了解组织工程处理的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以表征肌肉骨骼组织的功能完整性。总之，这种新知识对于推进肌肉骨骼疾病的治疗和诊断至关重要，例如退化性椎间盘疾病，骨关节炎和骨质疏松症，这些疾病会损害加拿大老龄化的人的流动性，并会极大地影响生活质量和整体健康。