EAGER: Which Mechanical Signals do Bone Micro Damage near Microcracks Send to Osteocytes?

EAGER：微裂纹附近的骨微损伤会向骨细胞发送哪些机械信号？

• 批准号: 1214816
• 负责人: Elisa Budyn
• 金额: $ 7.77万
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1214816&HistoricalAwards=false
• 关键词: EAGER; Mechanical; Signals; do; Bone

The research objective of this EArly-Concept Grant for Exploratory Research (EAGER) is to validate theoretical hypotheses on bone failure mechanism at the mineralised fibril level in order to precisely measure the in situ mechanical signals to bone cells (osteocytes) and to detect possible variations among humans in collagen and mineral strengths. Bone is a living tissue with a complex and highly heterogeneous microstructure resulting from the continuous self-healing process called remodeling. Osteocytes are mechano-sensitive cells suspected to initiate remodeling upon detection of micro damage in their environment that is composed of an organic phase of non-collagen proteins and collagen fibrils that are mineralised by hydroxyapatite crystals. Studies under this award will follow a top-down approach applying a dual experimental and numerical method to test and model micro cracks and micro damage growing in fresh human bone. The method will quantify in situ the local mechanical stress field created by progressing micro cracks and micro damage near osteocytes in bone under mechanical load. If successful, this research will determine how human bone mechanically bears load at the collagen and hydroxyapatite level and how the mechanical signals produced in situ by micro damage could possibly stimulate osteocytes to initiate the tissue biological response. The precise measurement of the mechanical effects of micro damage in the osteocyte's natural environment is transformative in that it advances the general understanding of the role of mechanical stimuli in cell biology. When applied to elderly patients this will further help to genetically trace the tissue mechanics changes in different components of bone to advance regenerative therapies and bone tissue engineering. The educational plan includes the mentoring of graduate students in bone micro biomechanics and an international collaboration with leading institutions in bone experimental research.

EARLY概念探索性研究资助（EAGER）的研究目标是在矿化纤维水平上验证骨衰竭机制的理论假设，以精确测量骨细胞（骨细胞）的原位机械信号，并检测人类胶原蛋白和矿物质强度的可能变化。骨是一种具有复杂和高度异质微观结构的活组织，其由称为重塑的连续自我愈合过程产生。骨细胞是机械敏感性细胞，怀疑在检测到其环境中的微损伤时启动重塑，所述环境由非胶原蛋白和胶原纤维的有机相组成，所述胶原纤维由羟基磷灰石晶体矿化。该奖项下的研究将遵循自上而下的方法，应用双重实验和数值方法来测试和模拟新鲜人骨中生长的微裂纹和微损伤。该方法将在原位量化局部机械应力场，所述局部机械应力场由在机械载荷下骨中骨细胞附近的微裂纹和微损伤产生。如果成功的话，这项研究将确定人类骨骼如何在胶原和羟基磷灰石水平上机械地承受载荷，以及微损伤原位产生的机械信号如何可能刺激骨细胞启动组织生物学反应。在骨细胞的自然环境中的微损伤的机械效应的精确测量是变革性的，因为它推进了细胞生物学中的机械刺激的作用的一般理解。当应用于老年患者时，这将进一步有助于从基因上追踪骨的不同成分中的组织力学变化，以推进再生治疗和骨组织工程。教育计划包括指导研究生在骨微生物力学和国际合作与领先的机构在骨实验研究。