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

University Of Kentucky Research Foundation, Lexington KY

Investigators

Abstract

0952915 Saunders Throughout 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.