The relative influence of material and architectural properties on the mechanical behavior of bone tissue.

摘要

Bone tissue exhibits a unique multiscale hierarchical composite structure. The material, or extracellular matrix, constituent phases of water, collagen, and apatite bone mineral are organized and preferentially oriented over several length scales to optimally bear and distribute mechanical loads in the skeleton. At larger length scales, the architecture of bone is continually remodeled through the creation of pore space and deposition of new tissue. However, aging and metabolic bone diseases such as osteoporosis can compromise the mechanical integrity of bone by altering the material and/or architectural properties of bone. Therefore, decoupling these structure-function relationships in bone provides mechanistic insights and elucidates which are most important when developing pharmacological treatments for metabolic bone disease.;This dissertation investigated the relative contributions of material and architectural properties on the mechanical behavior of bone tissue using combined numerical and experimental techniques. A micromechanical model and finite element analyses were used to decouple the relative influences of apatite crystal orientations and intracortical porosity (Ct.Po) on the elastic anisotropy of human cortical bone. The dominant and less variable transverse isotropy was governed primarily by material-level apatite crystal orientations, while the more subtle and variable orthotropy was governed primarily by Ct.Po. Micro-computed tomography (micro-CT) based finite element models of human trabecular bone specimens were used to investigate the effect of constitutive models on apparent and tissue-level yielding. Yield strains and yielding modalities exhibited minimal dependence on material constitutive model in comparison to architecture. Novel experimental methods for sequential micro-CT imaging and mechanical loading were used to investigate the relative influence of Ct.Po and mineralization on damage accumulation and fracture susceptibility in human cortical bone. Fractures were shown to initiate at fatigue microdamage that was spatially adjacent to elevated Ct.Po, but not elevated mineralization. Finite element models were subsequently used to examine the relative contributions of Ct.Po, mineralization, and fatigue microdamage on the stress concentrations at fracture initiation sites. Elevated stresses at the fracture initiation sites were governed by the coupled effects of Ct.Po and fatigue microdamage, but not mineralization. Finally, in vivo rabbit ulnar loading was developed and validated as a new model for preclinical investigations of bone mechanobiology which includes intracortical remodeling similar to human bone biology. Lamellar bone formation in rabbit ulnae exhibited a tightly controlled dose-dependent response to strains induced by mechanical loading.