Date of Award
Doctor of Philosophy (PhD)
Biomedical and Chemical Engineering
Biomedical Engineering and Bioengineering | Engineering
Bone is a highly calcified organic-inorganic composite tissue with complicated hierarchical structure. The presence of complex multi-cellular organization within opaque mineralized matrix makes it challenging to use conventional methods to study in vivo bone physiology even using model animals. To address this challenge, numerous in vitro models have been developed to study bone physiology under well-defined and repeatable experimental conditions although proving their physiological relevance remains a key challenge. This work aims to design and develop new in vitro models that better represent in vivo bone physiology with defined control over chemical and physical microenvironments, at low costs and high throughput. Chapter 1 provides an introduction about bone structure and function, while Chapters 2 to 4 describe in detail the process of new model development and its utility. Chapter 2 presents a perfusion-based co-culture model system for bone tissue engineering. Here gelatin hydrogel with co-cultured osteoblast-like and endothelial cells were used to study the roles of media perfusion on mineral deposition. Chapter 3 establishes a model system to investigate in vivo and in vitro mineralization processes. Here new relationships between electrical impedance of deposited mineral in both cell-mineralized and cell-free mineralized samples were discovered. Chapter 4 presents a model to study how osteocyte networks respond to shear flow under in vivo like confined conditions. Here we identified several distinct patterns of calcium signaling responses that vary across networks of interconnected osteocytes which have not been described previously. Chapter 5 is a summary of the completed work. Lastly, Chapter 6 discusses future directions to improve the models and potential applications for the models in solving bone physiology questions.
Zhang, Kairui, "Advanced in Vitro Models for Studying Bone Physiology" (2022). Dissertations - ALL. 1577.