Grant: Discovery Grants Program - Individual

Background: Comprehension of basic bone material structure resulting from remodeling processes is necessary for understanding complex aspects of bone adaptation, mechanical properties, and bone function. A knowledge gap exists regarding the 3D organization of human cortical bone microstructural and cellular networks in skeletal elements other than the rib and femur. To fill this gap, this proposal aims to explore differences in the cellular-level ultrastructure from all recognized bone types (e.g., flat, irregular, long, short, sesamoid) from adults of middle to older age, and the impact these changes have on bone remodeling, bone quality, and mechanical properties. Goal I: To operationalize the use of high-resolution synchrotron micro-Computed Tomography and confocal laser scanning microscopic imaging to describe the morphological variability of bone's vascular canal and cellular networks within various human bones as they relate to mechanical material properties (e.g., elastic modulus, fracture toughness). We will test the hypothesis that microstructural and mechanical properties will vary between bones, particularly for skeletal elements exposed to increased biomechanical strain (e.g., temporal, femur, tibia). Goal II: To quantitatively map lacuno-canalicular network parameters (e.g., density, connectivity) among bone types and integrate these novel ultrastructural data into a multiscale model of bone remodeling including mechanoregulatory feedback of osteocytes for cortical bone. We will test the hypothesis that changes in lacunar size and canalicular connectivity contribute to altered remodeling with advancing age and decreased bone quality (e.g., bone loss). HQP: The training plan will emphasize flexibility, inclusion, collaboration, and interdisciplinarity to create a strong social support system for each HQP. The proposed use of Canada's only synchrotron (CLS) provides an opportunity for HQPs to learn essential interpersonal and professional skills and thrive in a high-tech, fast-paced team environment. In addition, HQPs will 1) receive training in 3D data acquisition and image processing, and 2) have the opportunity to take non-traditional courses in human anatomy and osteology, enhancing their knowledge of bone macro- and micromorphology and fracture properties relevant to this project. Significance: The proposed research builds upon a longstanding collaboration between the principal investigator and CLS. The skeletal archive available for this work, developed and curated by Dr. Andronowski, is an unparalleled modern human tissue sample unique to Canada. A significant enhancement to this work will include a sophisticated multi-scale computational model which allows us to include experimental information from the cellular structure of bone. This work will generate new fundamental natural science knowledge in bone biology and advance the training of the next generation of diverse musculoskeletal researchers at MUN and beyond.