Date of Award

Fall 2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

Harris, Gerald F.

Second Advisor

Schmidt, Taly G.

Third Advisor

Molthen, Robert C.

Abstract

Osteogenesis imperfecta (OI) is a genetic disorder primarily associated with mutations to type I collagen and resulting in mild to severe bone fragility. To date, there is very little data quantifying OI cortical bone mechanics. The purpose of this dissertation was to investigate bone microstructure, mineralization, and mechanical properties in adolescents with OI. Characterization studies were performed on small osteotomy specimens obtained from the extremities during routine corrective surgeries. Nanoindentation was used to examine the longitudinal elastic modulus and hardness at the material level for mild OI type I vs. severe OI type III. Both modulus and hardness were significantly higher (by 7% and 8%, respectively) in mild OI cortical bone compared to the more severe phenotype. Lamellar microstructure also affected these properties, as the younger bone material immediately surrounding osteons showed decreased modulus (13%) and hardness (11%) compared to the older interstitial material. A high resolution micro-computed tomography system utilizing synchrotron radiation (SRµCT) was described and used to analyze the microscale vascular porosity, osteocyte lacunar morphometry, and bone mineral density in OI vs. healthy individuals. Vascular porosity, canal diameter, and osteocyte lacunar density were all two to six times higher in OI cortical bone. Osteocytes were also more spherical in shape. Finally, three-point bending techniques were used to evaluate the microscale mechanical properties of OI cortical bone in two different orientations. Elastic modulus, flexural yield strength, ultimate strength, and crack-growth toughness were three to six times higher in specimens whose pore structure was primarily oriented parallel vs. perpendicular to the long bone axis. There was also a strong negative correlation between the elevated vascular porosity of OI cortical bone and its elastic modulus, flexural yield strength, and ultimate strength. This relationship was independent of osteocyte lacunar density and tissue mineral density. In summary, these findings highlight new material and microstructural changes within OI cortical bone that help contribute to its fragility. They also underscore a deep connection between bone structure and mechanical integrity at multiple length scales.

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