Mineralized Collagen Fibrils: An Essential Component in Determining the Mechanical Behavior of Cortical Bone.

Bone comprises mechanically different materials in a specific hierarchical structure. Mineralized collagen fibrils (MCFs), represented by tropocollagen molecules and hydroxyapatite nanocrystals, are the fundamental unit of bone. The mechanical characterization of MCFs provides the unique adaptive mechanical competence to bone to withstand mechanical load. The structural and mechanical role of MCFs is critical in the deformation mechanisms of bone and the marvelous strength and toughness possessed by bone. However, the role of MCFs in the mechanical behavior of bone across multiple length scales is not fully understood. In the present study, we shed light upon the latest progress regarding bone deformation at multiple hierarchical levels and emphasize the role of MCFs during bone deformation. We propose the concept of hierarchical deformation of bone to describe the interconnected deformation process across multiple length scales of bone under mechanical loading. Furthermore, how the deterioration of bone caused by aging and diseases impairs the hierarchical deformation process of the cortical bone is discussed. The present work expects to provide insights on the characterization of MCFs in the mechanical properties of bone and lays the framework for the understanding of the multiscale deformation mechanics of bone.

Aging exacerbates the morphological and mechanical response of mineralized collagen fibrils in murine cortical bone to disuse.

Mineralized collagen fibrils (MCFs) are the fundamental building blocks of bone tissue and contribute significantly to the mechanical behavior of bone. However, it is still largely unknown how the collagen network in bone responds to aging and the disuse normally accompanying it. Utilizing atomic force microscopy, nanoindentation and Raman spectroscopy, age-related alterations in the microstructure and mechanical properties of murine cortical tibia at multiple scales were investigated in this study. The potential difference in the responses of bone to disuse at different ages was studied. The results indicated that the age- and disuse-related alterations in bone initiate from MCFs in the bone matrix. The D-periodic spacing, radial elastic modulus of a single MCF and the mineral-to-matrix ratio on the cortical bone surface were larger in aged mice than in adult mice. Disuse, on the other hand, mainly has a major influence on aged mice, particularly on the morphology and mechanical properties of MCFs, but it only has modest effects on adult bone. These findings revealed insights into the morphological and mechanical adaptation of mineralized collagen fibrils in murine cortical bone to aging and disuse. STATEMENT OF SIGNIFICANCE: Bone is a complex structured composite material consisting of an interwoven framework of collagen fibrils reinforced by mineral particles and embedded in an extrafibrillar mineralized matrix. Utilizing atomic force microscopy, nanoindentation and Raman spectroscopy, this study suggests that the effects of aging, as well as the accompanying disuse, on the morphology and mechanical properties of bone initiate from the mineralized collagen fibril level. More interestingly, the MCF in the bone of aged mice seems to be more sensitive to disuse than that in adult mice. These findings significantly further the current understanding of the adaptation process of bone to aging at the mineralized collagen fibril level and provide direct insights into the physiological response of bone to aging and the abnormal mechanical environment.

Disuse Impairs the Mechanical Competence of Bone by Regulating the Characterizations of Mineralized Collagen Fibrils in Cortical Bone.

Bones are made of complex material comprising organic components and mineral hydroxyapatite, both of which formulate the unique hierarchical structure of bone and its mechanical properties. Bones are capable of optimizing their structure and mechanical properties according to the mechanical environment. Mineral loss is a well-known consequence of skeleton disuse. By contrast, the response of the non-mineral phase of bone, i.e., the collagen network, during disuse remain largely unknown. In this study, a tail-suspension mice model was used to induce bone loss. Atomic force microscopy-based imaging and indentation approaches were adopted to investigate the influence of disuse on the morphology and in situ mechanical behavior of the collagen fibrils, under both non-loaded and load-bearing conditions, in the cortical tibia of mice. The results indicate that disuse induced by hindlimb unloading did not alter the orientation and D-periodic spacing of the collagen fibril, but results in decreased collagen crosslinking which correlates with decreased elasticity and increased susceptibility to mechanical damage. More concretely, the collagen fibrils in the disused tibia were misaligned under mechanical loading. It therefore indicates that the disordered arrangement of the mineralized collagen fibrils is one of the characteristics of the weakened bone during elastic deformation. These findings reveals the unique adaptation regimes of the collagen fibrils in the cortical bone to disuse, as well as the deformation mechanisms of bone in the relevant pathological process at different scales.