ABSTRACTBone is a natural protein (collagen)-mineral (hydroxyapatite) nanocomposite with hierarchically organized structure. Our previous work has demonstrated orientational differences in stoichiometry of hydroxyapatite resulting from orientationally dependent collagen-mineral interactions in bone. The nature of these interactions has been investigated both through molecular dynamics simulations as well as nanomechanical and infrared spectroscopic experiments. In this study, we report experimental studies on human cortical bone with osteogenesis imperfecta (OI), a disease characterized by fragility of bones and other tissues rich in type I collagen. About 90% of OI cases result from causative variant in one of the two structural genes (COL1A1 or COL1A2) for type I procollagens. OI provides an interesting platform for investigating how alterations of collagen at the molecular level cause changes in structure and mechanics of bone. Fourier transform spectroscopy, electron microscopy (SEM), and nanomechanical experiments describe the structural and molecular differences in bone ultrastructure due to presence of diseases. Photoacoustic-Fourier transform infrared spectroscopy (PA-FTIR) experiments have been conducted to investigate the orientational differences in molecular structure of OI bone, which is also compared with that of healthy human cortical bone. Further, in situ SEM static nanomechanical testing is conducted in the transverse and longitudinal directions in the OI bone. Microstructural defects and abnormities of OI bone were ascertained using scanning electron microscopies. These results provide an insight into molecular basis of deformation and mechanical behavior of healthy human bone and OI bone.
