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

在人的整个生命过程中，骨细胞都能感知并对其机械环境做出反应。虽然这种反应明显表现为运动后骨量增加，瘫痪和长期太空飞行时骨量减少，但它也潜移默化地出现在重塑中，即骨骼不断被替换或翻转的状态。重塑也是骨病的核心。例如，骨质疏松症与衰老不平衡有关，在这种情况下，随着更多的骨骼被移除而不是被替换，随之而来的是净骨丢失。旨在揭示重塑发生的机制和途径的实验室模型通常专注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载荷的生物学反应有了更多的了解，人们认为嵌入在骨基质中的骨细胞可以感受到刺激，并分别与破骨细胞和成骨细胞相互作用，从而移除和替换骨。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。鉴于骨转换不是一个直接的过程，而且负责这些变化的破骨细胞和成骨细胞在骨表面并不同时存在，因此需要一个可能同时在时间和空间上调节的体外模型。随着最近微平台的发展，这种模型的开发现在成为可能。在该项目中，将开发一个骨重建的微观全分析系统平台，以更准确地反映多细胞相互作用和生物环境。具体地说，破骨细胞和成骨细胞对骨细胞负载的直接反应将被研究，沟通的作用，一种可能的信号协调机制将被调查。这项研究更广泛的影响是开发了一个微平台，在这个平台中，可以在机械诱导的骨重建环境中研究骨多细胞相互作用，从而使从现象学到生物学模型的研究势在必行。更广泛的教育影响包括将骨骼机械生物学纳入大学水平的课程、研究生研究和高中生/教师实习。此外，一个主要的教育重点将是实施一项计划，通过实践活动向服务不足的农村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.