Experimental validation of a microcracking-based toughening mechanism for cortical bone

It has been proposed that cortical bone derives its toughness by forming microcracks during the process of crack propagation (J. Biomech. 30 (1997) 763; J. Biomech. 33 (2000) 1169). The purpose of this study was to experimentally validate the previously proposed microcrack-based toughening mechanism in cortical bone. Crack initiation and propagation tests were conducted on cortical bone compact tension specimens obtained from the antlers of red deer. For these tests, the main fracture crack was either propagated to a predetermined crack length or was stopped immediately after initiating from the notch. The microcracks produced in both groups of specimens were counted in the same surface area of interest around and below the notch, and crack growth resistance and crack propagation velocity were analyzed. There were more microcracks in the surface area of interest in the propagation than in initiation specimens showing that the formation of microcracks continued after the initiation of a fracture crack. Crack growth resistance increased with crack extension, and crack propagation velocity vs. crack extension curves demonstrated the characteristic jump increase and decrease pattern associated with the formation of microcracks. The scanning electron micrographs of crack initiation and propagation displayed the formation of a frontal process zone and a wake, respectively. These results support the microcrack-based toughening mechanism in cortical bone. Bone toughness is, therefore, determined by its ability to form microcracks during fracture.     

Advances in the fracture mechanics of cortical bone

As cortical bone is a semi-brittle solid, its fracture is dependent not only on the magnitude of the applied stress, but also on the nature of any intrinsic or introduced cracks. Consequently a variety of fracture mechanics techniques have been utilised to evaluate the fracture toughness of cortical bone, including the single edge notched, centre notched cylindrical and compact tension methods, and values have been established for the critical stress intensity factor (Kc) and the critical strain energy release rate (Gc). The Kc and Gc values obtained depend on the orientation of the cortical bone, as well as on bone density, the velocity of crack propagation and specimen geometry. The significance of these fracture mechanics parameters for cortical bone is critically reviewed.     

Effects and mechanisms of wakefulness on local cortical networks

Mammalian brains generate internal activity independent of environmental stimuli. Internally generated states may bring about distinct cortical processing modes. To investigate how brain state impacts cortical circuitry, we recorded intracellularly from the same neurons, under anesthesia and subsequent wakefulness, in rat barrel cortex. In every cell examined throughout layers 2-6, wakefulness produced a temporal pattern of synaptic inputs?differing markedly from those under anesthesia. Recurring periods of synaptic quiescence, prominent under anesthesia, were abolished by wakefulness, which produced instead a persistently depolarized state. This switch in dynamics was unaffected by elimination of afferent synaptic input from thalamus, suggesting that arousal alters cortical dynamics by neuromodulators acting directly on cortex. Indeed, blockade of noradrenergic, but not cholinergic, pathways induced synaptic quiescence during wakefulness. We conclude that global brain states can switch local recurrent networks into different regimes via direct neuromodulation.     

Microcracking damage and the fracture process in relation to strain rate in human cortical bone tensile failure

It is difficult to define the 'physiological' mechanical properties of bone. Traumatic failures in-vivo are more likely to be orders of magnitude faster than the quasistatic tests usually employed in-vitro. We have reported recently [Hansen, U., Zioupos, P., Simpson, R., Currey, J.D., Hynd, D., 2008. The effect of strain rate on the mechanical properties of human cortical bone. Journal of Biomechanical Engineering/Transactions of the ASME 130, 011011-1-8] results from tests on specimens of human femoral cortical bone loaded in tension at strain rates (epsilon ) ranging from low (0.08s(-1)) to high (18s(-1)). Across this strain rate range the modulus of elasticity generally increased, stress at yield and failure and strain at failure decreased for rates higher than 1s(-1), while strain at yield was invariant for most strain rates and only decreased at rates higher than 10s(-1). The results showed that strain rate has a stronger effect on post-yield deformation than on initiation of macroscopic yielding. In general, specimens loaded at high strain rates were brittle, while those loaded at low strain rates were much tougher. Here, a post-test examination of the microcracking damage reveals that microcracking was inversely related to the strain rate. Specimens loaded at low strain rates showed considerable post-yield strain and also much more microcracking. Partial correlation and regression analysis suggested that the development of post-yield strain was a function of the amount of microcracking incurred (the cause), rather than being a direct result of the strain rate (the excitation). Presumably low strain rates allow time for microcracking to develop, which increases the compliance of the specimen, making them tougher. This behaviour confirms a more general rule that the degree to which bone is brittle or tough depends on the amount of microcracking damage it is able to sustain. More importantly, the key to bone toughness is its ability to avoid a ductile-to-brittle transition for as long as possible during the deformation. The key to bone's brittleness, on the other hand, is the strain and damage localisation early on in the process, which leads to low post-yield strains and low-energy absorption to failure.     

Equine cortical bone exhibits rising R-curve fracture mechanics

Previous studies of the fracture properties of cortical bone have suggested that the fracture toughness increases with crack length, which is indicative of rising R-curve behavior. Based on this indirect evidence and the similarity of bone to ceramic matrix composites, we hypothesized that bone would exhibit rising R-curve behavior in the transverse orientation and that the characteristics of the R-curves would be regionally dependent within the cortex due to variations in bone microstructure and toughening mechanisms. To test these hypotheses, we conducted R-curve experiments on specimens from equine third metacarpal bones using standard fracture mechanics testing methods. Compact type specimens from the dorsal and lateral regions in the middle of the diaphysis were oriented for crack propagation transverse to the longitudinal axis of the bone.The test results demonstrate that equine cortical bone exhibits rising R-curve behavior during transverse crack propagation as hypothesized. Statistical analyses of the crack growth initiation toughness, K0, the peak toughness, Kpeak, and the crack extension at peak toughness, deltaa, revealed significant regional differences in these characteristics. Specifically, the lateral cortex displayed higher crack growth initiation and peak toughnesses. The dorsal cortex exhibited greater crack extension at the peak of crack growth resistance. Scanning electron microscopy revealed osteon pullout on fracture surfaces from the dorsal cortex and but not in the lateral cortex. Taken together, the significant differences in R-curves and the SEM fractography indicate that the fracture mechanisms acting in equine cortical bone are regionally dependent.     

Molecular and cellular mechanisms of human cortical connectivity

Comparative studies of the cerebral cortex have identified various human and primate-specific changes in both local and long-range connectivity, which are thought to underlie our advanced cognitive capabilities. These changes are likely mediated by the divergence of spatiotemporal regulation of gene expression, which is particularly prominent in the prenatal and early postnatal human and non-human primate cerebral cortex. In this review, we describe recent advances in characterizing human and primate genetic and cellular innovations including identification of novel species-specific, especially human-specific, genes, gene expression patterns, and cell types. Finally, we highlight three recent studies linking these molecular changes to reorganization of cortical connectivity.     

Measurement of the microstructural fracture toughness of cortical bone using indentation fracture

The purpose of this work is to investigate the use of indentation fracture as a method of measuring toughness at the microscale in cortical bone. Indentation fracture employs sharp indenters to initiate cracks, whose length can be used to calculate the toughness of the material. Only a cube corner indenter tip is found to initiate cracks at a suitable size scale for microstructural measurement. Cracks from 7 to 56 microm in length are produced using loads from 0.05 to 3N. Preliminary data predicts rising toughness with increasing crack length (rising R-curve behaviour) at the microscale. This technique provides a new insight into fracture in cortical bone since it allows the investigator to observe mechanisms and measure toughness at a size scale at which in vivo damage is known to exist.     

Orientation dependence of the fracture mechanics of cortical bone

The fracture mechanics parameter of the critical stress intensity factor (Kc) was determined by a modified compact tension test method, for the fracture of bovine tibia cortical bone at orientations of 0 degrees, 15 degrees, 30 degrees, 45 degrees, 75 degrees and 90 degrees to the bone axis. It was established that, for a given loading rate, a variation in orientation from 0-90 degrees produced average increases in Kc from 3.2 to 6.5 MN m-3/2.     

Compliance calibration for fracture testing of equine cortical bone

An experimental compliance calibration method for measuring crack length in fracture toughness tests of cortical bone was developed. Calibration tests were conducted on twenty compact type fracture specimens machined from the mid-diaphysis of five pairs of equine third metacarpal bones. Specimens were oriented for crack propagation in a direction transverse to the longitudinal axis of the bone. Specimen compliance was determined from the load vs. crack opening displacement record over a range of crack lengths from 0.48 to 0.75 times the specimen width. The results demonstrate that the compliance calibration method developed for isotropic materials can be used to determine crack length in bone, which is transversely isotropic. However, specimens from lateral and dorsal regions exhibited significantly different compliance calibrations even after differences in elastic modulus were taken into account in the normalized compliance.     

Age-dependent fatigue behaviour of human cortical bone

Despite a general understanding that bone quality contributes to skeletal fragility, very little information exits on the age-dependent fatigue behavior of human bone. In this study four-point bending fatigue tests were conducted on aging bone in conjunction with the analysis of stiffness loss and preliminary investigation of nanoindentation based measurements of local tissue stiffness and histological evaluation of resultant tensile and compressive damage to identify the damage mechanism responsible for the increase in age-related bone fragility. The results obtained show that there is an exponential decrease in fatigue life with age, and old bone exhibits different modulus degradation profiles than young bone. In addition, this study provides preliminary evidence indicating that during fatigue loading, younger bone formed diffuse damage, lost local tissue stiffness on the tensile side. Older bone, in contrast, formed linear microcracks lost local tissue stiffness on the compressive side. Thus, the propensity of aging human bone to form more linear microcracks than diffuse damage may be a significant contributor to bone quality, and age related fragility in bone.     

Some viscoplastic characteristics of bovine and human cortical bone

Multiple cycle tensile creep tests were performed on human and bovine cortical bone specimens. The tests enabled total strain to be decomposed into elastic, linear viscoelastic, creep and permanent plastic components. The results indicate that a stress threshold exists; above which time dependent effects dominate material response and below which the behavior is primarily linear viscoelastic, with time effects playing only a secondary role. A constant stress above the threshold produces a constant steady state creep rate, with the magnitude of the creep rate being an exponential function of the stress magnitude. Additionally, it was found that a major portion of the inelastic strain is always recovered on unloading and that the accumulation of creep strain increases the material compliance on subsequent loadings below the threshold. These two factors suggest that a damage mechanism is responsible for the nonlinear behavior.     

WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ～2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2 × 10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3 × 10(-12), and -0.16 SD per G allele, P = 1.2 × 10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3 × 10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9 × 10(-6) and rs2707466: OR = 1.22, P = 7.2 × 10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5 × 10(-13)相似文献   

Propagation of surface fatigue cracks in human cortical bone

An understanding of how fatigue cracks grow in bone is of importance as fatigue is thought to be the main cause of clinical stress fractures. This study presents new results on the fatigue-crack growth behavior of small surface cracks (approximately 75-1000 microm in size) in human cortical bone, and compares their growth rates with data from other published studies on the behavior of both surface cracks and many millimeter, through-thickness large cracks. Results are obtained with a cyclically loaded cantilever-beam geometry using optical microscopy to examine for crack growth after every 100-500 cycles. Based on the current and previous results, small fatigue cracks appear to become more resistant to fatigue-crack growth with crack extension, analogous to the way the fracture resistance of cortical bone increases with crack growth. Mechanistically, a theory attributing such behavior to the development of bridges in the wake of the crack with crack growth is presented. The existence of such bridges is directly confirmed using optical microscopy.     

Mineralized collagen fibril network spatial arrangement influences cortical bone fracture behavior

Bone is a hierarchical material exhibiting different fracture mechanisms at each length scale. At the submicroscale, the bone is composed of mineralized collagen fibrils (MCF). At this scale, the fracture processes in cortical bone have not been extensively studied in the literature. In this study, the influence of MCF size and orientation on the fracture behavior of bone under both transverse and longitudinal loading was investigated using novel 3D models of MCF networks with explicit representation of extra-fibrillar matrix. The simulation results showed that separation between MCFs was the main cause of damage and failure under transverse loading whereas under longitudinal loading, the main damage and failure mechanism was MCF rupture. When the MCF network was loaded in the transverse direction the mechanical properties increased as the orientation of fibrils deviated farther from the main fibril orientation whereas the opposite trend was observed under longitudinal loading. The fracture energy was much larger in longitudinal than transverse loading. MCF diameter variation did not affect the mechanical properties under longitudinal loading but led to higher mechanical properties with increasing MCF diameter under transverse loading. The new modeling framework established in this study generate unique information on the effect of MCF network spatial arrangement on the fracture behavior of bone at the submicroscale which is not currently possible to measure via experiments. This unique information may improve the understanding of how structural alterations at the submicroscale due to disease, age-related changes, and treatments affect the fracture processes at larger length scales.     

Simulation of creep in non-homogenous samples of human cortical bone

Characterising the mechanisms causing viscoelastic mechanical properties of human cortical bone, as well as understanding sources of variation, is important in predicting response of the bone to creep and fatigue loads. Any better understanding, when incorporated into simulations including finite element analysis, would assist bioengineers, clinicians and biomedical scientists. In this study, we used an empirically verified model of creep strain accumulation, in a simulation of 10 non-homogeneous samples, which were created from micro-CT scans of human cortical bone of the femur midshaft obtained from a 74-year-old female cadaver. These non-homogeneous samples incorporate the presence of Haversian canals and resorption cavities. The influence of inhomogeneity on the response and variation in the samples in both creep and stress relaxation tests are examined. The relationship between steady-state creep rate, applied loads (stress relaxation and creep tests) and microstructure, that is bone apparent porosity, is obtained. These relations may provide insight into damage accumulation of whole human bones and be relevant to studies on osteoporosis.     

Simulation of creep in non-homogenous samples of human cortical bone

Characterising the mechanisms causing viscoelastic mechanical properties of human cortical bone, as well as understanding sources of variation, is important in predicting response of the bone to creep and fatigue loads. Any better understanding, when incorporated into simulations including finite element analysis, would assist bioengineers, clinicians and biomedical scientists. In this study, we used an empirically verified model of creep strain accumulation, in a simulation of 10 non-homogeneous samples, which were created from micro-CT scans of human cortical bone of the femur midshaft obtained from a 74-year-old female cadaver. These non-homogeneous samples incorporate the presence of Haversian canals and resorption cavities. The influence of inhomogeneity on the response and variation in the samples in both creep and stress relaxation tests are examined. The relationship between steady-state creep rate, applied loads (stress relaxation and creep tests) and microstructure, that is bone apparent porosity, is obtained. These relations may provide insight into damage accumulation of whole human bones and be relevant to studies on osteoporosis.