Mechanochemical Sensation of Damage in the Pericellular Niche

该奖项的目的是了解细胞针对受损骨骼区域进行修复的机制。作为日常活动的一部分，骨骼会受到微小的损伤，细胞通过持续的修复过程来抑制微裂纹的积累。最近的研究表明，钙是从受损的骨骼区域释放出来的，这种释放可能会启动骨修复级联反应。这个项目将建立在这一洞察力的基础上，并将表征骨细胞对骨骼释放钙的反应。结合起来，这些研究将描绘出一幅更完整的图景，统一从基质中释放钙，确定钙进入细胞的途径，以及钙运输时被激活的分子类型。成功实现该奖项的目标将提高我们对驱动骨骼修复的机制的理解。对骨骼修复的洞察创造了缓解骨骼脆弱性的各种条件的可能性，包括骨质疏松症。与奖项相关的活动的另一个好处是为设计智能生物材料创造了基础，这种材料可以通过调节细胞反应来自我修复。如果观察到受损基质中的钙释放触发了细胞的基质修复，那么所提出的活动将促进设计类似骨的材料，从而诱导常驻细胞修复关键负荷的区域。女性参与工程职业的人数一直在增加；然而，这种参与需要持续到未来。在外展方面，高中女生将参加研究活动，以培养她们追求工程职业的兴趣。

The objective of this award is to understand the mechanisms by which cells target the damaged regions of bone for repair. The skeleton sustains microscopic damage as part of daily activities and cells curb microcrack accumulation by a continual repair process. Recent studies demonstrated that calcium is released from damaged regions of bone and such a release may initiate bone-repair cascade. This project will build on this insight and will characterize the response of bone cells to calcium release from bone. In combination, the studies will draw a more complete picture which unifies calcium release from the matrix, identify the route via which calcium enters the cells and the types of molecules which are activated upon calcium transport. Successful attainment of the aims of this award will improve our understanding of the mechanisms which drive skeletal repair. Insight on skeletal repair creates the potential to mitigate various conditions of skeletal fragility, including osteoporosis. Another merit of award-related activities is the creation of the foundation for designing intelligent biomaterials which can repair themselves by regulating cell response. If observed calcium release from damaged substrate triggers matrix-repair by cells, the proposed activities would cultivate efforts to design bone like materials which induce resident cells to repair critically loaded regions. Female participation in engineering careers has been increasing; however, this engagement needs to be sustained into the future. On the outreach front, high-school female students will participate in research activities to foster their interests in pursuing careers in engineering.