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

在个体的一生中，骨细胞感知并响应它们的机械环境。虽然这种反应在运动导致骨量增加和瘫痪和长期太空飞行导致骨量减少方面很明显，但它也微妙地表现在骨骼重塑方面，即骨骼不断被替换或翻转的情况。骨重塑也是骨病的核心。例如，骨质疏松症与衰老失衡有关，在这种情况下，骨质流失会随着骨质流失而增加。旨在揭示骨重塑发生的机制和途径的实验室模型通常聚焦于单一的骨细胞类型，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感知刺激，并与破骨细胞和成骨细胞相互作用，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仿生物环境。鉴于骨转换不是一个直接的过程，并且负责这些变化的破骨细胞和成骨细胞并不是同时在骨表面发现的，因此需要一个可能在时间和空间上都受到调节的体外模型。随着最近微平台的发展，这种模型的开发现在成为可能。在本项目中，将开发一个骨重塑的微总量分析系统平台，以更准确地反映多细胞相互作用和生物环境。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，并将研究信号协调的一种可能机制——通信的作用。这项研究的更广泛的影响在于开发了一个微平台，在这个微平台中，骨多细胞相互作用可以在机械诱导的骨重塑环境中进行研究，从而实现从现象学到生物学建模的必要转变。更广泛的教育影响包括将骨力学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，通过实践活动向服务不足地区的农村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.