"Molecular Level Structure-function Properties of Cortical Bone Based on Hydration and Disease State" 

Elizabeth Montagnino, MSE PhD Candidate 

Advisor: Professor John Howarter

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ABSTRACT

The burden from skeletal fractures on social, economic, and healthcare systems motivates the investigation into the nanoscale material properties and deformation mechanisms for bone fracture prevention. As a living biological material, healthy bones continually remodel and turnover; aging and disease can lead to disrupted organ performance, which prevents proper remodeling. This can lead to a breakdown of bone quality (material properties) and elevate skeletal fragility. As a material, bone’s hierarchal mixed material composition is organized into distinct yet integrated macro, micro, and nanoscale structures. Whole bone geometry along with macro porosity differs by bone type and skeletal function. The microstructure varies between compact and spongy bone where compact has an ordered lamellar structure while spongy bone has higher levels of porosity from a woven structure for more disordered arrangement. Mineralized collagen fibrils are formed by type-I collagen and carbonated apatite, in a ~67 nm periodic D-spacing, with an area of micro-fibril overlap and gap where mineral platelet clusters nucleate. Current clinical models use bone mineral density for bone strength assessments, though deformation begins with the mineralized collagen matrix. Bone’s strength comes from the apatite, viscoelasticity from the hydrated collagen, and toughness originates from the interface between the collagen and mineral. Developing fracture and disease models for the human skeletal system has traditionally been based on accessible animal studies, which provide limited information to the human model, due to differences in physiological needs as well as material and mechanical properties. This work focuses on tuning the mineralized collagen fibril structure-function properties with small molecule exposure in the native and diseased state for murine and human cortical bone. The nanostructure was studied with small and wide-angle x-ray scattering. The alterations in mineralized fibril pre-strain state in unloaded tests and fibril strain relative applied macroscopic strain with in-situ testing were evaluated. Structural changes with varied hydration and mineralization levels provided the ability to monitor the interaction between treatments and the contribution of each phase to the structure-function relationship. Complimentary characterization methods, thermogravimetric analysis, and Raman spectroscopy were used to investigate the composition and chemical alterations with treatment. Small molecule treatment resulted in changes to the mineral quality and microfibril structure, which translated to a higher interaction between the collagen and mineral in the pre-strain and loaded state. The stronger coupling of collagen and minerals provides insight into potential methods to reverse bone quality degradation and improve deformation mechanisms.