The role of collagen in bone structure: an image processing approach

Bone collagen structure in normal and pathological tissues is presented using techniques of thin section transmission electron microscopy and morphometry. In pathological tissue, deviations from normal fine structure are reflected in abnormal arrangements of collagen fibrils and abnormalities in fibril diameter. The relationships between these bone structural changes and the skeletal calcium/phosphorus ratio are discussed. Calcium/phosphorus ratio is measured by X-ray absorptiometry and computed microtomography.

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Bone Architecture: Collagen Structure and Calcium/Phosphorus Maps

AlloDerm, a processed acellular human tissue matrix, is used in a number of surgical applications for tissue repair and regeneration. In the present work, AlloDerm serves as a model system for studying gamma radiation-induced changes in tissue structure and stability as well as the effect of such changes on the cell-matrix interactions, including cell repopulation and matrix remodeling. AlloDerm tissue matrix was treated with 2-30 kGy gamma irradiation at room temperature. Gamma irradiation reduced the swelling of tissue matrix upon rehydration and caused significant structural modifications, including collagen condensation and hole formation in collagen fibres. The tensile strength of AlloDerm increased at low gamma dose but decreased with increasing gamma dosage. The elasticity of irradiated AlloDerm was reduced significantly. Calorimetric study showed that gamma irradiation destabilized the tissue matrix, resulting in greater susceptibility to proteolytic enzyme degradation. Although gamma irradiation did not affect in vitro proliferation of fibroblast cells, it promoted tissue degradation upon cell repopulation and influenced synthesis and deposition of new collagen.

Alterations of human acellular tissue matrix by gamma irradiation: histology, biomechanical property, stability, in vitro cell repopulation, and remodeling.

Bone mineral density is the gold-standard for assessing bone quantity and diagnosing osteoporosis. Although bone mineral density measurements assess the quantity of bone, the quality of the tissue is an important predictor of fragility. Understanding the macro- and nanoscale properties of bone is critical to understanding bone fragility in osteoporosis. Osteoporosis is a disease that affects more than 75 million people worldwide. The gold standard for osteoporosis prognosis, bone mineral density, primarily measures the quantity of bone in the skeleton, overlooking more subtle aspects of bone's properties. Bone quality, a measure of bone's architecture, geometry and material properties, is evaluated via mechanical, structural and chemical testing. Although decreased BMD indicates tissue fragility at the clinical level, changes in the substructure of bone can help indicate how bone quality is altered in osteoporosis. Additionally, mechanical properties which can quantify fragility, or bone's inability to resist fracture, can be changed due to alterations in bone architecture and composition. Recent studies have focused on examination of bone on the nanoscale, suggesting the importance of understanding the interactions of the mineral crystals and collagen fibrils and how they can alter bone quality. It is therefore important to understand alterations in bone that occur at the macro-, micro- and nanoscopic levels to determine what parameters contribute to decreased bone quality in diseased tissue.

The effect of the microscopic and nanoscale structure on bone fragility

Regenerative medicine leverages the innate potential of the human body to efficiently repair and regenerate damaged tissues using engineered biomaterials. By designing responsive biomaterials with the appropriate biophysical and biochemical characteristics, cellular response can be modulated to direct tissue healing. Recently, inorganic biomaterials have been shown to regulate cellular responses including cell-cell and cell-matrix interactions. Moreover, ions released from these mineral-based biomaterials play a vital role in defining cell identity, as well as driving tissue-specific functions. The intrinsic properties of inorganic biomaterials, such as the release of bioactive ions (e.g., Ca, Mg, Sr, Si, B, Fe, Cu, Zn, Cr, Co, Mo, Mn, Au, Ag, V, Eu, and La), can be leveraged to induce phenotypic changes in cells or modulate the immune microenvironment to direct tissue healing and regeneration. Biophysical characteristics of biomaterials, such as topography, charge, size, electrostatic interactions, and stiffness can be modulated by addition of inorganic micro- and nanoparticles to polymeric networks have also been shown to play an important role in their biological response. In this Review, we discuss the recent emergence of inorganic biomaterials to harness the innate regenerative potential of the body. Specifically, we will discuss various biophysical or biochemical effects of inorganic-based materials in directing cellular response for regenerative medicine applications.

Inorganic Biomaterials for Regenerative Medicine.

In vivo measurement of radius calcium/phosphorus ratio by X-ray absorptiometry

The effects of inflammation-mediated osteoporosis (IMO) on the skeletal Ca/P ratio and on the structure of rabbit bone and skin collegen

The structure of mouse skin collagen fibrils after treatment with 0.5, 1 and 2.5 Gy gamma-irradiation was studied by electron microscopy. Animals were sacrificed 1, 4 and 8 weeks after irradiation. Although there were areas where the normal parallel packing of fibrils was retained in some regions packing was interrupted by abnormal fibrils and in some cases helical twisting was apparent. Irradiated collagen fibrils had a lower mean diameter compared with normal and a large variability in width. The diameter of 0.5 Gy irradiated fibrils returned to normal by 4 or 8 weeks after irradiation. Clusters of abnormal fibrils were found when viewed in cross-sections. Their number and size was reversibly dependent on the dose level. All fibrils retained normal banding periodicity. Computer analysis of irradiated and control patterns led to the conclusion that 0.5-2.5 Gy gamma-irradiation had no considerable effect in modifying the charge distribution along the mouse skin collagen fibril.

Influence of low doses of gamma-irradiation on mouse skin collagen fibrils

The influence of Inflammation Mediated Osteopenia (IMO) on rabbit skin and bone (trabecular and cortical) collagen fibrils was studied by electron microscopy. Severe abnormalities in collagen fibril structure were detected, at the ultrastructural level, in skin and bone specimens from IMO rabbits. In treated animals the arrangement of fibrils is anarchic. The overall collagen fibril architecture is disturbed compared to normal. IMO collagen fibrils' mean diameter values were significantly larger than those from controls, in all examined tissues. However, the banding patterns of fibrils were normal in all cases. Computer analysis shows no differences in charged amino acid composition between IMO and untreated samples. Our results show a correlation between the effects induced by osteopenia on skin and bone collagen.

Evangelia Kounadi

Papers

In vivo measurement of radius calcium/phosphorus ratio by X-ray absorptiometry

The effects of inflammation-mediated osteoporosis (IMO) on the skeletal Ca/P ratio and on the structure of rabbit bone and skin collegen

Influence of low doses of gamma-irradiation on mouse skin collagen fibrils

The Influence of Inflammation-Mediated Osteopenia (IMO) on the Structure of Rabbit Bone and Skin Collagen Fibrils

An electron microscopic study of collagen fibril structure after lithium treatment--I. The effect of different lithium doses on mouse skin collagen.