Tracking Cell Fate during Mechanically Directed Bone Regeneration In Vivo

该奖项的研究目标是量化骨损伤的机械环境及其与损伤部位骨骼祖细胞反应的相关性。骨骼祖细胞在骨折和其他骨骼损伤的愈合中起主要作用，并且可以根据其局部环境中的刺激分化成多种定向细胞类型之一。计划中的研究将应用来自工程学和生物学的实验和计算工具的组合来标记损伤部位的祖细胞，量化这些细胞所在组织的机械环境，并识别特定的机械刺激（例如，剪切应变、压力等）与这些细胞的募集和它们的不同命运有关。这些研究将确定非常有利于特定类型骨骼组织（如骨、软骨和纤维组织）形成的力学条件。这些研究将加快基础和临床研究的几个领域的发现步伐，包括确定可促进骨愈合的力学环境，揭示机械刺激影响细胞分化的机制，以及鉴定用于增强骨形成的新类型的分子靶标。这些途径中的每一个都针对减轻由骨损伤引起的个人和经济成本，特别是由这些损伤的不良愈合引起的个人和经济成本。该项目的教育部分包括初级科学家和工程师的培训-两名研究生和三名本科生将接受该研究项目的指导-以及加强对科学和定量研究领域感兴趣的低收入高中女生的成功的寄宿暑期计划。该计划的内容是由大学教职员工，行业合作伙伴关系，并在工程力学和生物力学课程注册的本科生和研究生设计的外展模块提供。

The research objective of this award is to quantify the mechanical environment of a bone injury and its association with the response of skeletal progenitor cells at the injury site. Skeletal progenitor cells play a principal role in healing of bone fractures and other skeletal injuries and can differentiate into one of multiple, committed cell types depending on stimuli in their local environment. The planned studies will apply a combination of experimental and computational tools from engineering and biology to label progenitor cells at the injury site, to quantify the mechanical environment of the tissues in which these cells reside, and to identify the specific mechanical stimuli (e.g., shear strain, pressure, etc.) associated with the recruitment of these cells and their various fates. These studies will define the mechanical conditions highly favorable to formation of a given type of skeletal tissue, such as bone, cartilage, and fibrous tissue.These studies will accelerate the pace of discovery in several areas of basic and clinical research, including defining mechanical environments that can promote bone healing, uncovering the mechanisms by which mechanical stimuli can influence cell differentiation, and identifying new classes of molecular targets for enhancing bone formation. Each of these avenues is directed towards alleviating the personal and economic costs arising from bone injuries, and in particular, from poor healing of these injuries. The educational components of the project consist of training of junior scientists and engineers-two graduate students and three undergraduate students will be mentored on this research project-and on enhancing a successful, residential summer program for low-income, high-school girls interested in scientific and quantitative fields of study. Content for the program is supplied by university faculty and staff, industry partnerships, and outreach modules designed by undergraduate and graduate students enrolled in courses in engineering mechanics and biomechanics.