Ani Ural

Dilatational band formation in bone

Toughening in hierarchically structured materials like bone arises from the arrangement of constituent material elements and their interactions. Unlike microcracking, which entails micrometer-level separation, there is no known evidence of fracture at the level of bone’s nanostructure. Here, we show that the initiation of fracture occurs in bone at the nanometer scale by dilatational bands. Through fatigue and indentation tests and laser confocal, scanning electron, and atomic force microscopies on human and bovine bone specimens, we established that dilatational bands of the order of 100 nm form as ellipsoidal voids in between fused mineral aggregates and two adjacent proteins, osteocalcin (OC) and osteopontin (OPN). Laser microdissection and ELISA of bone microdamage support our claim that OC and OPN colocalize with dilatational bands. Fracture tests on bones from OC and/or OPN knockout mice (OC−/−, OPN−/−, OC-OPN−/−;−/−) confirm that these two proteins regulate dilatational band formation and bone matrix toughness. On the basis of these observations, we propose molecular deformation and fracture mechanics models, illustrating the role of OC and OPN in dilatational band formation, and predict that the nanometer scale of tissue organization, associated with dilatational bands, affects fracture at higher scales and determines fracture toughness of bone.

Effects of Intracortical Porosity on Fracture Toughness in Aging Human Bone: A μCT-Based Cohesive Finite Element Study

The extent to which increased intracortical porosity affects the fracture properties of aging and osteoporotic bone is unknown. Here, we report the development and application of a microcomputed tomography based finite element approach that allows determining the effects of intracortical porosity on bone fracture by blocking all other age-related changes in bone. Previously tested compact tension specimens from human tibiae were scanned using microcomputed tomography and converted to finite element meshes containing three-dimensional cohesive finite elements in the direction of the crack growth. Simulations were run incorporating age-related increase in intracortical porosity but keeping cohesive parameters representing other age-related effects constant. Additional simulations were performed with reduced cohesive parameters. The results showed a 6% decrease in initiation toughness and a 62% decrease in propagation toughness with a 4% increase in porosity. The reduction in toughnesses became even more pronounced when other age-related effects in addition to porosity were introduced. The initiation and propagation toughness decreased by 51% and 83%, respectively, with the combined effect of 4% increase in porosity and decrease in the cohesive properties reflecting other age-related changes in bone. These results show that intracortical porosity is a significant contributor to the fracture toughness of the cortical bone and that the combination of computational modeling with advanced imaging improves the prediction of the fracture properties of the aged and the osteoporotic cortical bone.

Fracture mechanics approach to facesheet delamination in honeycomb: measurement of energy release rate of the adhesive bond

Abstract Two types of experiments were designed and performed to evaluate the adhesive bond in honeycomb sandwich panels. The tensile bond strength between the facesheet and the core was determined through the flatwise tension test. The fracture toughness of the bond line was measured through the double cantilever beam test. Fracture toughness values varied for different facesheet thicknesses and core materials. Toughness was also different for the bag and tool sides of the panels for all specimen types.

A direct role of collagen glycation in bone fracture

Non-enzymatic glycation (NEG) is an age-related process accelerated by diseases like diabetes, and causes the accumulation of advanced glycation end-products (AGEs). NEG-mediated modification of bones organic matrix, principally collagen type-I, has been implicated in impairing skeletal physiology and mechanics. Here, we present evidence, from in vitro and in vivo models, and establish a causal relationship between collagen glycation and alterations in bone fracture at multiple length scales. Through atomic force spectroscopy, we established that NEG impairs collagens ability to dissipate energy. Mechanical testing of in vitro glycated human bone specimen revealed that AGE accumulation due to NEG dramatically reduces the capacity of organic and mineralized matrix to creep and caused bone to fracture under impact at low levels of strain (3000-5000 μstrain) typically associated with fall. Fracture mechanics tests of NEG modified human cortical bone of varying ages, and their age-matched controls revealed that NEG disrupted microcracking based toughening mechanisms and reduced bone propagation and initiation fracture toughness across all age groups. A comprehensive mechanistic model, based on experimental and modeling data, was developed to explain how NEG and AGEs are causal to, and predictive of bone fragility. Furthermore, fracture mechanics and indentation testing on diabetic mice bones revealed that diabetes mediated NEG severely disrupts bone matrix quality in vivo. Finally, we show that AGEs are predictive of bone quality in aging humans and have diagnostic applications in fracture risk.

THE EFFECT OF STRAIN RATE ON FRACTURE TOUGHNESS OF HUMAN CORTICAL BONE: A FINITE ELEMENT STUDY

Evaluating the mechanical response of bone under high loading rates is crucial to understanding fractures in traumatic accidents or falls. In the current study, a computational approach based on cohesive finite element modeling was employed to evaluate the effect of strain rate on fracture toughness of human cortical bone. Two-dimensional compact tension specimen models were simulated to evaluate the change in initiation and propagation fracture toughness with increasing strain rate (range: 0.08-18 s(-1)). In addition, the effect of porosity in combination with strain rate was assessed using three-dimensional models of micro-computed tomography-based compact tension specimens. The simulation results showed that bones resistance against the propagation of a crack decreased sharply with increase in strain rates up to 1 s(-1) and attained an almost constant value for strain rates larger than 1 s(-1). On the other hand, initiation fracture toughness exhibited a more gradual decrease throughout the strain rates. There was a significant positive correlation between the experimentally measured number of microcracks and the fracture toughness found in the simulations. Furthermore, the simulation results showed that the amount of porosity did not affect the way initiation fracture toughness decreased with increasing strain rates, whereas it exacerbated the same strain rate effect when propagation fracture toughness was considered. These results suggest that strain rates associated with falls lead to a dramatic reduction in bones resistance against crack propagation. The compromised fracture resistance of bone at loads exceeding normal activities indicates a sharp reduction and/or absence of toughening mechanisms in bone during high strain conditions associated with traumatic fracture.

Finite Element Modeling of Microcrack Growth in Cortical Bone

Bone is similar to fiber-reinforced composite materials made up of distinct phases such as osteons (fiber), interstitial bone (matrix), and cement lines (matrix-fiber interface). Microstructural features including osteons and cement lines are considered to play an important role in determining the crack growth behavior in cortical bone. The aim of this study is to elucidate possible mechanisms that affect crack penetration into osteons or deflection into cement lines using fracture mechanics-based finite element modeling. Cohesive finite element simulations were performed on two-dimensional models of a single osteon surrounded by a cement line interface and interstitial bone to determine whether the crack propagated into osteons or deflected into cement lines. The simulations investigated the effect of (i) crack orientation with respect to the loading, (ii) fracture toughness and strength of the cement line, (iii) crack length, and (iv) elastic modulus and fracture properties of the osteon with respect to the interstitial bone. The results of the finite element simulations showed that low cement line strength facilitated crack deflection irrespective of the fracture toughness of the cement line. However, low cement line fracture toughness did not guarantee crack deflection if the cement line had high strength. Long cracks required lower cement line strength and fracture toughness to be deflected into cement lines compared with short cracks. The orientation of the crack affected the crack growth trajectory. Changing the fracture properties of the osteon influenced the crack propagation path whereas varying the elastic modulus of the osteon had almost no effect on crack trajectory. The findings of this study present a computational mechanics approach for evaluating microscale fracture mechanisms in bone and provide additional insight into the role of bone microstructure in controlling the microcrack growth trajectory.

Hierarchical perspective of bone toughness – from molecules to fracture

Abstract Osteoporotic and age-related fractures are a significant public health problem. The current standard of osteoporosis assessment via bone mineral density has been shown to be inadequate for fracture risk predictions highlighting the importance of material composition and structural design of bone in determining skeletal fragility. Bone is a hierarchical material that derives its fracture resistance from various mechanisms that act at length scales ranging from nano- to macroscale. Recent research efforts have focussed on the understanding of bone fracture based on this hierarchical structure to provide a more reliable assessment of fracture risk. Understanding the function, contribution and interaction of each length scale to bone toughness is a crucial step to develop new strategies for fracture risk assessment, fracture prevention, and development of therapeutic interventions for disease and age-related changes in bone. This review presents a hierarchical perspective of bone toughness ranging from nano- to macroscale and reports on the current state of knowledge in the areas of experimental and computational approaches to bone fracture.

Interaction of microstructure and microcrack growth in cortical bone: a finite element study

Microstructural features including osteons and cement lines are considered to play an important role in determining the crack growth behaviour in cortical bone. This study aims to develop a computational mechanics approach to evaluate microscale fracture mechanisms in bone. In this study, finite element models based on actual human cortical bone images that allow for arbitrary crack growth were utilised to determine the crack propagation behaviour. The simulations varied the cement line and osteon strength and fracture toughness in different bone microstructures to assess the crack propagation trajectory, stress–strain relationship and nonlinear strain energy density. The findings of this study provide additional insight into the individual influence of microstructural features and their properties on crack growth behaviour in bone using a computational approach.

Association between non-enzymatic glycation, resorption, and microdamage in human tibial cortices

SummaryTo better understand the association between different components of bone quality, we investigated the relationship among in vivo generated non-enzymatic glycation, resorption, and microdamage. The results showed negative correlation between advanced glycation end-products (AGEs) and resorption independent of age highlighting the interaction between these parameters that may lead to bone fragility.IntroductionChanges in the quality of bone material contribute significantly to bone fragility. In order to establish a better understanding of the interaction of the different components of bone quality and their influence on bone fragility, we investigated the relationship between non-enzymatic glycation, resorption, and microdamage generated in vivo in cortical bone using bone specimens from the same donors.MethodsTotal fluorescent advanced glycation end-products (AGEs) were measured in 96 human cortical bone samples from 83 donors. Resorption pit density, average resorption pit area, and percent resorption area were quantified in samples from 48 common donors with AGE measurements. Linear microcrack density and diffuse damage were measured in 21 common donors with AGE and resorption measurements. Correlation analyses were performed between all measured variables to establish the relationships among them and their variation with age.ResultsWe found that average resorption pit area and percent resorption area decreased with increasing AGEs independently of age. Resorption pit density and percent resorption area demonstrated negative age-adjusted correlation with diffuse damage. Furthermore, average resorption pit area, resorption pit density, and percent resorption area were found to decrease significantly with age.ConclusionsThe current study demonstrated the in vivo interrelationship between the organic constituents, remodeling, and damage formation in cortical bone. In addition to the age-related reduction in resorption, there is a negative correlation between AGEs and resorption independent of age. This inverse relationship indicates that AGEs alter the resorption process and/or accumulate in the tissue as a result of reduced resorption and may lead to bone fragility by adversely affecting fracture resistance through altered bone matrix properties.

A new fracture assessment approach coupling HR-pQCT imaging and fracture mechanics-based finite element modeling.

A new fracture assessment approach that combines HR-pQCT imaging with fracture mechanics-based finite element modeling was developed to evaluate distal radius fracture load. Twenty distal radius images obtained from postmenopausal women (fracture, n=10; nonfracture, n=10) were processed to obtain a cortical and a whole bone model for each subject. The geometrical properties of each model were evaluated and the corresponding fracture load was determined under realistic fall conditions using cohesive finite element modeling. The results showed that the whole bone fracture load can be estimated based on the cortical fracture load for nonfracture (R(2)=0.58, p=0.01) and pooled data (R(2)=0.48, p<0.001) but not for the fracture group. The portion of the whole bone fracture load carried by the cortical bone increased with increasing cortical fracture load (R(2)≥0.5, p<0.05) indicating that a more robust cortical bone carries a larger percentage of whole bone fracture load. Cortical thickness was found to be the best predictor of both cortical and whole bone fracture load for all groups (R(2) range: 0.49-0.96, p<0.02) with the exception of fracture group whole bone fracture load showing the predictive capability of cortical geometrical properties in determining whole bone fracture load. Fracture group whole bone fracture load was correlated with trabecular thickness (R(2)=0.4, p<0.05) whereas the nonfracture and the pooled group did not show any correlation with the trabecular parameters. In summary, this study introduced a new modeling approach that coupled HR-pQCT imaging with fracture mechanics-based finite element simulations, incorporated fracture toughness and realistic fall loading conditions in the models, and showed the significant contribution of the cortical compartment to the overall fracture load of bone. Our results provide more insight into the fracture process in bone and may lead to improved fracture load predictions.