In Vitro-Induced High Sugar Environments Deteriorate Human Cortical Bone Elastic Modulus and Fracture Toughness.
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ABSTRACT:
SUBMITTER: Merlo K
PROVIDER: S-EPMC7162721 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The incidence of bone fracture increases with age, due to both declining bone quantity and quality. Toward the goal of an improved understanding of the causes of the age-related decline in the fracture toughness of male cortical bone, nanoindentation experiments were performed on femoral diaphysis specimens from men aged 21-98 years. Because aged bone has less matrix-bound water and dry bone is less viscoelastic, we used a nanoindentation method that is sensitive to changes in viscoelasticity. Given the anisotropy of bone stiffness, longitudinal (n = 26) and transverse (n = 25) specimens relative to the long axis of the femur diaphysis were tested both dry in air and immersed in phosphate buffered saline solution. Indentation stiffness (storage modulus) and hardness increased with age, while viscoelasticity (loss modulus) was independent of donor age. The increases in indentation stiffness and hardness with age were best explained by increased mineralization with age. Indentation stiffness and hardness were negatively correlated with previously acquired fracture toughness parameters, which is consistent with a tradeoff between material strength and toughness. In keeping with the complex structure of bone, a combination of tissue-level storage modulus or hardness, bound water, and osteonal area in regression models best explained the variance in the fracture toughness of male human cortical bone. On the other hand, viscoelasticity was unchanged with age and was not associated with fracture toughness. In conclusion, the age-related increase in stiffness and hardness of male cortical bone may be one of the multiple tissue-level characteristics that contributes to decreased fracture toughness.
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Project description:An orb web's prey capture thread features tiny glue droplets, each formed of an adhesive glycoprotein core surrounded by an aqueous layer. Small molecules in the aqueous layer confer droplet hygroscopicity and maintain glycoprotein viscoelasticity, causing droplet volume and glycoprotein performance to track changes in environmental humidity. Droplet extension combines with that of a thread's supporting flagelliform fibers to sum the adhesive forces of multiple droplets, creating an effective adhesive system. We combined measurements of the force on an extending droplet, as gauged by the deflection of its support line, with measurements of glycoprotein volume and droplet extension to determine the Young's modulus (E) and toughness of three species' glycoproteins. We did this at five relative humidities between 20-90% to assess the effect of humidity on these properties. When droplets of a thread span extend, their extensions are constrained and their glycoprotein filaments remain covered by aqueous material. This was also the case during the first extension phase of the individual droplets that we examined. However, as extension progressed, the aqueous layer was progresses disrupted, exposing the glycoprotein. During the first extension phase E ranged from 0.00003 GPa, a value similar to that of fibronectin, a glycoprotein that anchors cells in the extracellular matrix, to 0.00292 GPa, a value similar to that of resilin in insect ligaments. Second phase E increased 4.7-19.4-fold. When compared at the same humidity the E of each species' glycoprotein was less than 5% of the value reported for its flagelliform fibers. This difference may facilitate the coordinated extension of these two capture thread components that is responsible for summing the thread's adhesive forces.
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Project description:This paper examines the effect of surface treatment and filler shape factor on the fracture toughness and elastic modulus of epoxy-based nanocomposite. Two forms of nanofillers, polydopamine-coated montmorillonite clay (D-clay) and polydopamine-coated carbon nanofibres (D-CNF) were investigated. It was found that Young's modulus increases with increasing D-clay and D-CNF loading. However, the fracture toughness decreases with increased D-clay loading but increases with increased D-CNF loading. Explanations have been provided with the aid of fractographic analysis using electron microscope observations of the crack-filler interactions. Fractographic analysis suggests that although polydopamine provides a strong adhesion between the fillers and the matrix, leading to enhanced elastic stiffness, the enhancement prohibits energy release via secondary cracking, resulting in a decrease in fracture toughness. In contrast, 1D fibre is effective in increasing the energy dissipation during fracture through crack deflection, fibre debonding, fibre break, and pull-out.
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Project description:Greater understanding of the determinants of skeletal fragility is highly sought due to the great burden that bone affecting diseases and fractures have on economies, societies and health care systems. Being a complex, hierarchical composite of collagen type-I and non-stoichiometric substituted hydroxyapatite, bone derives toughness from its organic phase. In this study, we tested whether early observations that a strong correlation between bone collagen integrity measured by thermomechanical methods and work to fracture exist in a more general and heterogeneous sampling of the population. Neighboring uniform specimens from an established, highly characterized and previously published collection of human cortical bone samples (femur mid-shaft) were decalcified in EDTA. Fifty-four of the original 62 donors were included (26 male and 28 females; ages 21-101?years; aging, osteoporosis, diabetes and cancer). Following decalcification, bone collagen was tested using hydrothermal isometric tension (HIT) testing in order to measure the collagen's thermal stability (denaturation temperature, Td) and network connectivity (maximum rate of isometric tension generation; Max.Slope). We used linear regression and general linear models (GLMs) with several explanatory variables to determine whether relationships between HIT parameters and generally accepted bone quality factors (e.g., cortical porosity, pentosidine content [pen], pyridinoline content [pyd]), age, and measures of fracture toughness (crack initiation fracture toughness, Kinit, and total energy release/dissipation rate evaluated at the point of unstable fast fracture, J-int) were significant. Bone collagen connectivity (Max.Slope) correlated well with the measures of fracture toughness (R2?=?24-35%), and to a lesser degree with bound water fraction (BW; R2?=?7.9%) and pore water fraction (PW; R2?=?9.1%). Significant correlations with age, apparent volumetric bone mineral density (vBMD), and mature enzymatic [pyd] and non-enzymatic collagen crosslinks [pen] were not detected. GLMs found that Max.Slope and vBMD (or BW), with or without age as additional covariate, all significantly explained the variance in Kinit (adjusted-R2?=?36.7-49.0%). Also, the best-fit model for J-int (adjusted-R2?=?35.7%) included only age and Max.Slope as explanatory variables with Max.Slope contributing twice as much as age. Max.Slope and BW without age were also significant predictors of J-int (adjusted-R2?=?35.5%). In conclusion, bone collagen integrity as measured by thermomechanical methods is a key factor in cortical bone fracture toughness. This study further demonstrates that greater attention should be paid to degradation of the overall organic phase, rather than a specific biomarker (e.g. [pen]), when seeking to understand elevated fracture rates in aging and disease.
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Project description:Developing clinical tools that assess bone matrix quality could improve the assessment of a person's fracture risk. To determine whether Raman spectroscopy (RS) has such potential, we acquired Raman spectra from human cortical bone using microscope- and fiber optic probe-based Raman systems and tested whether correlations between RS and fracture toughness properties were statistically significant. Calculated directly from intensities at wavenumbers identified by second derivative analysis, Amide I sub-peak ratio I1670/I1640, not I1670/I1690, was negatively correlated with Kinit (N = 58; R2 = 32.4%) and J-integral (R2 = 47.4%) when assessed by Raman micro-spectroscopy. Area ratios (A1670/A1690) determined from sub-band fitting did not correlate with fracture toughness. There were fewer correlations between RS and fracture toughness when spectra were acquired by probe RS. Nonetheless, the I1670/I1640 sub-peak ratio again negatively correlated with Kinit (N = 56; R2 = 25.6%) and J-integral (R2 = 39.0%). In best-fit general linear models, I1670/I1640, age, and volumetric bone mineral density explained 50.2% (microscope) and 49.4% (probe) of the variance in Kinit. I1670/I1640 and v1PO4/Amide I (microscope) or just I1670/I1640 (probe) were negative predictors of J-integral (adjusted-R2 = 54.9% or 37.9%, respectively). While Raman-derived matrix properties appear useful to the assessment of fracture resistance of bone, the acquisition strategy to resolve the Amide I band needs to be identified.
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Project description:A decline in the inherent quality of bone tissue is a † Equal contributors contributor to the age-related increase in fracture risk. Although this is well-known, the important biochemical factors of bone quality have yet to be identified using Raman spectroscopy (RS), a nondestructive, inelastic light-scattering technique. To identify potential RS predictors of fracture risk, we applied principal component analysis (PCA) to 558 Raman spectra (370-1720 cm-1) of human cortical bone acquired from 62 female and male donors (nine spectra each) spanning adulthood (age range = 21-101 years). Spectra were analyzed prior to R-curve, nonlinear fracture mechanics that delineate crack initiation (Kinit) from crack growth toughness (Kgrow). The traditional ν1phosphate peak per amide I peak (mineral-to-matrix ratio) weakly correlated with Kinit (r = 0.341, p = 0.0067) and overall crack growth toughness (J-int: r = 0.331, p = 0.0086). Sub-peak ratios of the amide I band that are related to the secondary structure of type 1 collagen did not correlate with the fracture toughness properties. In the full spectrum analysis, one principal component (PC5) correlated with all of the mechanical properties (Kinit: r = - 0.467, Kgrow: r = - 0.375, and J-int: r = - 0.428; p < 0.0067). More importantly, when known predictors of fracture toughness, namely age and/or volumetric bone mineral density (vBMD), were included in general linear models as covariates, several PCs helped explain 45.0% (PC5) to 48.5% (PC7), 31.4% (PC6), and 25.8% (PC7) of the variance in Kinit, Kgrow, and J-int, respectively. Deriving spectral features from full spectrum analysis may improve the ability of RS, a clinically viable technology, to assess fracture risk.
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Project description:Changes in the distribution of bone mineralization occurring with aging, disease, or treatment have prompted concerns that alterations in mineralization heterogeneity may affect the fracture resistance of bone. Yet, so far, studies assessing bone from hip fracture cases and fracture-free women have not reached a consensus on how heterogeneity in tissue mineralization relates to skeletal fragility. Owing to the multifactorial nature of toughening mechanisms occurring in bone, we assessed the relative contribution of heterogeneity in mineralization to fracture resistance with respect to age, porosity, and area fraction of osteonal tissue. The latter parameters were extracted from quantitative backscattered electron imaging of human cortical bone sections following R-curve tests of single-edge notched beam specimens to determine fracture toughness properties. Microstructural heterogeneity was determined as the width of the mineral distribution (bulk) and as the sill of the variogram (local). In univariate analyses of measures from 62 human donors (21 to 101 years), local but not bulk heterogeneity as well as pore clustering negatively correlated with fracture toughness properties. With age as covariate, heterogeneity was a significant predictor of crack initiation, though local had a stronger negative contribution than bulk. When considering all potential covariates, age, cortical porosity and area fraction of osteons explained up to 50% of the variance in bone?s crack initiation toughness. However, including heterogeneity in mineralization did not improve upon this prediction. The findings of the present work stress the necessity to account for porosity and microstructure when evaluating the potential of matrix-related features to affect skeletal fragility.
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Project description:Neurons change their growth dynamics and mechanical properties in response to external stimuli such as stiffness of the local microenvironment, ambient temperature, and biochemical or geometrical guidance cues. Here we use combined atomic force microscopy (AFM) and fluorescence microscopy experiments to investigate the relationship between external temperature, soma volume, and elastic modulus for cortical neurons. We measure how changes in ambient temperature affect the volume and the mechanical properties of neuronal cells at both the bulk (elastic modulus) and local (elasticity maps) levels. The experimental data demonstrate that both the volume and the elastic modulus of the neuron soma vary with changes in temperature. Our results show a decrease by a factor of 2 in the soma elastic modulus as the ambient temperature increases from room (25 °C) to physiological (37 °C) temperature, while the volume of the soma increases by a factor of 1.3 during the same temperature sweep. Using high-resolution AFM force mapping, we measure the temperature-induced variations within different regions of the elasticity maps (low and high values of elastic modulus) and correlate these variations with the dynamics of cytoskeleton components and molecular motors. We quantify the change in soma volume with temperature and propose a simple theoretical model that relates this change with variations in soma elastic modulus. These results have significant implications for understanding neuronal development and functions, as ambient temperature, cytoskeletal dynamics, and cellular volume may change with variations in physiological conditions, for example, during tissue compression and infections in vivo as well as during cell manipulation and tissue regeneration ex vivo.
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Project description:Fracture risk does not solely depend on strength but also on fracture toughness; ie, the ability of bone material to resist crack initiation and propagation. Because resistance to crack growth largely depends on bone properties at the tissue level, including collagen characteristics, current X-ray based assessment tools may not be suitable to identify age-related, disease-related, or treatment-related changes in fracture toughness. To identify useful clinical surrogates that could improve the assessment of fracture resistance, we investigated the potential of (1)H nuclear magnetic resonance spectroscopy (NMR) and reference point indentation (RPI) to explain age-related variance in fracture toughness. Harvested from cadaveric femurs (62 human donors), single-edge notched beam (SENB) specimens of cortical bone underwent fracture toughness testing (R-curve method). NMR-derived bound water showed the strongest correlation with fracture toughness properties (r = 0.63 for crack initiation, r = 0.35 for crack growth, and r = 0.45 for overall fracture toughness; p < 0.01). Multivariate analyses indicated that the age-related decrease in different fracture toughness properties were best explained by a combination of NMR properties including pore water and RPI-derived tissue stiffness with age as a significant covariate (adjusted R(2) = 53.3%, 23.9%, and 35.2% for crack initiation, crack growth, and overall toughness, respectively; p < 0.001). These findings reflect the existence of many contributors to fracture toughness and emphasize the utility of a multimodal assessment of fracture resistance. Exploring the mechanistic origin of fracture toughness, glycation-mediated nonenzymatic collagen crosslinks and intracortical porosity are possible determinants of bone fracture toughness and could explain the sensitivity of NMR to changes in fracture toughness. Assuming fracture toughness is clinically important to the ability of bone to resist fracture, our results suggest that improvements in fracture risk assessment could potentially be achieved by accounting for water distribution (quantitative ultrashort echo time magnetic resonance imaging) and by a local measure of tissue resistance to indentation, RPI.
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Project description:Amplification in toughness and balance with stiffness and strength are fundamental characteristics of biological structural composites, and a long sought-after objective for engineering design. Nature achieves these properties through a combination of multiscale key features. Yet, emulating all these features into synthetic de novo materials is rather challenging. Here, we fine-tune manual lamination, to implement a newly designed bone-inspired structure into fiber-reinforced composites. An integrated approach, combining numerical simulations, ad hoc manufacturing techniques, and testing, yields a novel composite with enhanced fracture toughness and balance with stiffness and strength, offering an optimal lightweight material solution with better performance than conventional materials such as metals and alloys. The results also show how the new design significantly boosts the fracture toughness compared to a classic laminated composite, made of the same building blocks, also offering an optimal tradeoff with stiffness and strength. The predominant mechanism, responsible for the enhancement of fracture toughness in the new material, is the continuous deviation of the crack from a straight path, promoting large energy dissipation and preventing a catastrophic failure. The new insights resulting from this study can guide the design of de novo fiber-reinforced composites toward better mechanical performance to reach the level of synergy of their natural counterparts.
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