CAREER: Hierarchies of Repair in Damaged Bone - A Role for Osteocytes

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。本教师早期职业发展（Career）项目的研究目标是建立三种不同机制在改善受损骨组织力学性能方面的相对贡献。评估的三种机制是：(a)通过称为建模的过程改变整个骨结构，(b)通过称为重塑的过程用新形成的完整组织替换受损组织，以及(c)通过嵌入骨中的称为“骨细胞”的细胞进行修复。这三种机制有望分别在数天、数周和数月的时间内，在毫米尺度、微尺度和纳米尺度上改善受损骨的力学性能。成果包括开发一种新的图像相关技术来确定骨骼内的应变，开发通过实验验证的分析和计算模型来分析三种不同修复机制的相对重要性，以及开发新的课程来教育和为学生和高中教师提供研究经验。如果成功，这项研究的结果将提供在不同长度和时间尺度上修复受损骨的层次结构的基本理解。这项研究将提供一种新的机制，可以有助于显著改善受损骨材料的性能，即由骨细胞介导的修复过程。这些研究将导致对影响骨质量的动态因素的认识，同时提供另一种细胞修复机制，可以通过药物来降低骨折风险。将提供研究生和本科生培训，并将研究成果纳入课堂。此外，PI还将结合实验室研究经验提供课堂教学，以扩大少数民族、高中生和K-12教师的参与。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The research objective of this Faculty Early Career Development (CAREER) project is to establish the relative contribution of three distinct mechanisms in improvement of damaged bone tissue mechanical properties. The three mechanisms evaluated are: (a) changes in whole bone structure by a process termed modeling, (b) replacement of damaged tissue with newly formed intact tissue by a process termed remodeling, and (c) repair by cells embedded in bone termed "osteocytes". These three mechanisms are expected to improve mechanical properties of damaged bone at the mm-scale, micro-scale and nano-scale over periods of days, weeks, and months, respectively. Deliverables include the development of a novel image correlation technique to determine strains within bone, development of analytical and computational models validated using experiments to analyze the relative importance of the three distinct repair mechanisms, and the development of new courses to educate and provide research experiences to students and high-school teachers. If successful, the results of this research will provide a fundamental understanding of the hierarchies of repair of damaged bone at different length- and time- scales. This research will provide insight into a novel mechanism that can contribute towards substantial improvement of damaged bone material properties, i.e. the repair process mediated by osteocytes. These studies will lead to knowledge regarding dynamic factors that affect bone quality, while providing another cellular repair mechanism that can be targeted by pharmaceuticals to reduce fracture risk. Graduate and undergraduate student training will be provided and research results incorporated into classes. In addition, the PI will provide classroom instruction in conjunction with laboratory research experiences to broaden participation by minorities, high-school students and K-12 teachers.