Experimental Evaluation of Multiscale Behavior of Human Bone
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Abstract
Bone is the most important structural member of the human body. It has a unique
hierarchical structure and its primary constituents, collagen molecules and hydroxyapatite, are
arranged in a staggered pattern at nanometer scale. Osteogenesis imperfecta (OI) is an inheritable
disease characterized by the fragility of bones and other tissues rich in the type I collagen. OI
provides an interesting platform for investigating how alterations of collagen at the molecular
level cause changes in the structure of bone. In this dissertation, multi-scale-, particularly
nanometer and sub-micro scale-, behaviors of both normal and OI (putative type I) human bones
have been evaluated experimentally. Since chemical treatment influences collagen or mineral
structure, we have used ―undisturbed bone samples‖ that are not subjected to any chemicals as
previously done in literature. Photoacoustic-Fourier transform infrared spectroscopy (PA-FTIR)
experiments reveal orientational differences in stoichiometry of hydroxyapatite. FTIR, electron
microscopy, scanning probe microscopy, and nanomechanical tests also show that the OI disease
results in a distorted microstructure in bone and that the mineralization of hydroxyapatite in OI is
also altered. Modulus mapping test displays the distribution of mineralized fibril and
extrafibrillar mineral according to the spatial variation of elastic properties. Dynamic
nanomechanical behaviors of OI bone and normal bone indicates that the viscoelasticity of intact
bone is mostly determined by the mineral. Also investigated are molecular composition and
nanomechanical properties of different anatomical positions in the diaphysis of an OI human
tibia. Our study on OI bone describes unique differences in collagen as previously described but
also elaborates on unique influence of the non-collagenous proteins on mineralization of bone in
OI. The fundamental premise of this work is investigation of the molecular basis of this highly
debilitating bone disease.