CAREER: A Biomimetic Micro Total Analysis System Platform of Bone Remodeling: Elucidating the Role of Cell Communication

0952915桑德斯在人的一生中，骨细胞感知并响应其力学环境。 虽然这种反应在运动引起的骨量增加和瘫痪和长期太空飞行引起的骨量减少中是明显的，但它也微妙地表现在重塑中，这是一种骨骼不断被替换或翻转的情况。重塑也是骨骼疾病的核心。 例如，骨质疏松症与衰老不平衡有关，其中净骨丢失加剧了更多的骨被移除而不是替换。 旨在揭示重塑发生的机制和途径的实验室模型通常集中在单个骨细胞类型，如成骨细胞。 随着我们对骨细胞对机械负荷的生物学反应的了解越来越多，嵌入骨基质中的骨细胞被认为能够感受到刺激并与破骨细胞和成骨细胞相互作用以分别去除和替换骨。 为了推进我们在这一领域的知识和发现，实验室模型必须准确地反映或模拟生物环境。 考虑到骨转换不是一个即时的过程，并且在骨表面上没有同时发现负责这些变化的破骨细胞和成骨细胞，因此需要一种可以在时间和空间上调节的体外模型。 随着微平台的发展，这种模式的发展现在是可能的。 本计画将开发一个骨重建的微全分析系统平台，以更准确地反映多细胞间的相互作用及生物环境。 具体而言，破骨细胞和成骨细胞对骨细胞负荷的直接反应将被检查，通信的作用，一种可能的信号协调机制将被研究。 这项研究的更广泛的影响是在一个微平台的开发，其中骨多细胞相互作用可以在机械诱导的骨重建环境中进行研究，使从现象学到生物学建模的必要性。 更广泛的教育影响包括将骨机械生物学纳入大学课程，研究生研究和高中学生/教师实习。 此外，一个主要的教育重点将是实施一项方案，通过实践活动向农村、服务不足地区的小学生介绍生物医学工程。

0952915SaundersThroughout and individual's life, bone cells sense and respond to their mechanical environment. While this response is evident in increased bone mass with exercise and decreased bone mass with paralysis and long-term spaceflight, it also subtly presents itself in remodeling, a condition in which bone is continually replaced, or turned over. Remodeling is also central in bone disease. For example, osteoporosis is linked to an aging imbalance in which a net bone loss ensues as more bone is removed than replaced. Laboratory models aimed at uncovering the mechanisms and pathways by which remodeling occurs often focus on a single bone cell type, such as the osteoblast. As we learn more about the biological response of bone cells to mechanical loading, the osteocytes, embedded in the bone matrix, are believed to sense the stimulation and interact with osteoclasts and osteoblasts to remove and replace the bone, respectively. In order to advance our knowledge and discovery in this field, the laboratory models must accurately reflect, or mimic the biological environment. Given that bone turnover is not an immediate process and that the osteoclasts and osteoblasts responsible for these changes are not concurrently found on the bone surface, an in vitro model is needed that may be both temporally and spatially regulated. With the recent development of microplatforms, this model development is now possible. Within this project, a micro total analysis system platform of bone remodeling will be developed to more accurately reflect the multicellular interactions and the biological environment. Specifically, the direct response of osteoclasts and osteoblasts to osteocyte loading will be examined and the role of communication, one possible mechanism of signal coordination will be investigated. The broader impact of this research is in the development of a microplatform in which the bone multicellular interactions may be studied in a mechanically-induced bone remodeling environment enabling the imperative move from phenomenological to biological modeling. The broader educational impacts include the incorporation of bone mechanobiology in college level coursework, graduate research and high school student/teacher internships. In addition, a major educational focus will be on the implementation of a program to introduce biomedical engineering to primary school children in rural, underserved areas through hands-on activities.