This PhD aimed at characterising mechanical, structural and compositional properties of cortical bone at the micro- and nano-scale employing various techniques applied to mouse models of ageing and disease.

Nanoindentation was used to probe bone at the micro-scale. Nanoindentation properties of the same control mouse bones were measured using a range of preparation, testing and analysis options. This was the first time that such systematic study was conducted. It was concluded that although the measured values were influenced by experimental and analysis choices, nanoindentation was capable of capturing relative trends in bone’s mechanical properties.

Nanoindentation was then coupled to a poroelastic approach to measure age-related changes in mouse bone permeability. Permeability is key to understanding fluid flow in bone, which may indicate how bone cells sense changes in the mechanical environment. These first permeability measurements in mouse bone demonstrated that the permeability caused by fluid flowing through bone’s lacunar-canalicular porosity decreases with age.

Porosity is expected to also affect bone’s ability to resist fracture at the micro-scale. The influence of intra-cortical porosity on crack propagation was explored via extended finite element methods. A novel technique was suggested to propagate cracks through holes and applied to 2D models of the porosity of osteogenesis imperfecta mouse bone. Results showed that vascular canals affect crack propagation and might contribute to the brittleness of osteogenesis impefecta bone.

Skeletal pathologies often cause alterations in bone’s building blocks leading to deteriorated whole-bone toughness. Mineral properties of brittle and ductile mouse bone (models of osteogenesis imperfecta and rickets respectively) were evaluated. Results revealed that deviations in size, composition and organisation of bone mineral reduce bone’s mechanical integrity both in brittle and ductile pathologic bone.

The outcomes of this thesis provide a deeper understanding of bone material, which is required for future improvements in treatments for skeletal diseases.