Validated respiratory drug deposition predictions from 2D and 3D medical images with statistical shape models and convolutional neural networks.

For the one billion sufferers of respiratory disease, managing their disease with inhalers crucially influences their quality of life. Generic treatment plans could be improved with the aid of computational models that account for patient-specific features such as breathing pattern, lung pathology and morphology. Therefore, we aim to develop and validate an automated computational framework for patient-specific deposition modelling. To that end, an image processing approach is proposed that could produce 3D patient respiratory geometries from 2D chest X-rays and 3D CT images. We evaluated the airway and lung morphology produced by our image processing framework, and assessed deposition compared to in vivo data. The 2D-to-3D image processing reproduces airway diameter to 9% median error compared to ground truth segmentations, but is sensitive to outliers of up to 33% due to lung outline noise. Predicted regional deposition gave 5% median error compared to in vivo measurements. The proposed framework is capable of providing patient-specific deposition measurements for varying treatments, to determine which treatment would best satisfy the needs imposed by each patient (such as disease and lung/airway morphology). Integration of patient-specific modelling into clinical practice as an additional decision-making tool could optimise treatment plans and lower the burden of respiratory diseases.

Relationship between CT-Derived Bone Mineral Density and UTE-MR-Derived Porosity Index in Equine Third Metacarpal and Metatarsal Bones.

Fatigue-related subchondral bone injuries of the third metacarpal/metatarsal (McIII/MtIII) bones are common causes of wastage, and they are welfare concerns in racehorses. A better understanding of bone health and strength would improve animal welfare and be of benefit for the racing industry. The porosity index (PI) is an indirect measure of osseous pore size and number in bones, and it is therefore an interesting indicator of bone strength. MRI of compact bone using traditional methods, even with short echo times, fail to generate enough signal to assess bone architecture as water protons are tightly bound. Ultra-short echo time (UTE) sequences aim to increase the amount of signal detected in equine McIII/MtIII condyles. Cadaver specimens were imaged using a novel dual-echo UTE MRI technique, and PI was calculated and validated against quantitative CT-derived bone mineral density (BMD) measures. BMD and PI are inversely correlated in equine distal Mc/MtIII bone, with a weak mean r value of -0.29. There is a statistically significant difference in r values between the forelimbs and hindlimbs. Further work is needed to assess how correlation patterns behave in different areas of bone and to evaluate PI in horses with and without clinically relevant stress injuries.

QCT-based computational bone strength assessment updated with MRI-derived 'hidden' microporosity.

Microdamage accumulated through sustained periods of cyclic loading or single overloading events contributes to bone fragility through a reduction in stiffness and strength. Monitoring microdamage in vivo remains unattainable by clinical imaging modalities. As such, there are no established computational methods for clinical fracture risk assessment that account for microdamage that exists in vivo at any specific timepoint. We propose a method that combines multiple clinical imaging modalities to identify an indicative surrogate, which we term 'hidden porosity', that incorporates pre-existing bone microdamage in vivo. To do so, we use the third metacarpal bone of the equine athlete as an exemplary model for fatigue induced microdamage, which coalesces in the subchondral bone. N = 10 metacarpals were scanned by clinical quantitative computed tomography (QCT) and magnetic resonance imaging (MRI). We used a patch-based similarity method to quantify the signal intensity of a fluid sensitive MRI sequence in bone regions where microdamage coalesces. The method generated MRI-derived pseudoCT images which were then used to determine a pre-existing damage (Dpex) variable to quantify the proposed surrogate and which we incorporate into a nonlinear constitutive model for bone tissue. The minimum, median, and maximum detected Dpex of 0.059, 0.209, and 0.353 reduced material stiffness by 5.9%, 20.9%, and 35.3% as well as yield stress by 5.9%, 20.3%, and 35.3%. Limb-specific voxel-based finite element meshes were equipped with the updated material model. Lateral and medial condyles of each metacarpal were loaded to simulate physiological joint loading during gallop. The degree of detected Dpex correlated with a relative reduction in both condylar stiffness (p = 0.001, R2 > 0.74) and strength (p < 0.001, R2 > 0.80). Our results illustrate the complementary value of looking beyond clinical CT, which neglects the inclusion of microdamage due to partial volume effects. As we use clinically available imaging techniques, our results may aid research beyond the equine model on fracture risk assessment in human diseases such as osteoarthritis, bone cancer, or osteoporosis.

In situ synchrotron radiation µCT indentation of cortical bone: Anisotropic crack propagation, local deformation, and fracture.

The development of treatment strategies for skeletal diseases relies on the understanding of bone mechanical properties in relation to its structure at different length scales. At the microscale, indention techniques can be used to evaluate the elastic, plastic, and fracture behaviour of bone tissue. Here, we combined in situ high-resolution SRµCT indentation testing and digital volume correlation to elucidate the anisotropic crack propagation, deformation, and fracture of ovine cortical bone under Berkovich and spherical tips. Independently of the indenter type we observed significant dependence of the crack development due to the anisotropy ahead of the tip, with lower strains and smaller crack systems developing in samples indented in the transverse material direction, where the fibrillar bone ultrastructure is largely aligned perpendicular to the indentation direction. Such alignment allows to accommodate the strain energy, inhibiting crack propagation. Higher tensile hoop strains generally correlated with regions that display significant cracking radial to the indenter, indicating a predominant Mode I fracture. This was confirmed by the three-dimensional analysis of crack opening displacements and stress intensity factors along the crack front obtained for the first time from full displacement fields in bone tissue. The X-ray beam significantly influenced the relaxation behaviour independent of the tip. Raman analyses did not show significant changes in specimen composition after irradiation compared to non-irradiated tissue, suggesting an embrittlement process that may be linked to damage of the non-fibrillar organic matrix. This study highlights the importance of three-dimensional investigation of bone deformation and fracture behaviour to explore the mechanisms of bone failure in relation to structural changes due to ageing or disease. STATEMENT OF SIGNIFICANCE: Characterising the three-dimensional deformation and fracture behaviour of bone remains essential to decipher the interplay between structure, function, and composition with the aim to improve fracture prevention strategies. The experimental methodology presented here, combining high-resolution imaging, indentation testing and digital volume correlation, allows us to quantify the local deformation, crack propagation, and fracture modes of cortical bone tissue. Our results highlight the anisotropic behaviour of osteonal bone and the complex crack propagation patterns and fracture modes initiating by the intricate stress states beneath the indenter tip. This is of wide interest not only for the understanding of bone fracture but also to understand other architectured (bio)structures providing an effective way to quantify their toughening mechanisms in relation to their main mechanical function.

The elasto-plastic nano- and microscale compressive behaviour of rehydrated mineralised collagen fibres.

The hierarchical design of bio-based nanostructured materials such as bone enables them to combine unique structure-mechanical properties. As one of its main components, water plays an important role in bone's material multiscale mechanical interplay. However, its influence has not been quantified at the length-scale of a mineralised collagen fibre. Here, we couple in situ micropillar compression, and simultaneous synchrotron small angle X-ray scattering (SAXS) and X-ray diffraction (XRD) with a statistical constitutive model. Since the synchrotron data contain statistical information on the nanostructure, we establish a direct connection between experiment and model to identify the rehydrated elasto-plastic micro- and nanomechanical fibre behaviour. Rehydration led to a decrease of 65%-75% in fibre yield stress and compressive strength, and 70% in stiffness with a 3x higher effect on stresses than strains. While in agreement with bone extracellular matrix, the decrease is 1.5-3x higher compared to micro-indentation and macro-compression. Hydration influences mineral more than fibril strain with the highest difference to the macroscale when comparing mineral and tissue levels. The effect of hydration seems to be strongly mediated by ultrastructural interfaces while results provide insights towards mechanical consequences of reported water-mediated structuring of bone apatite. The missing reinforcing capacity of surrounding tissue for an excised fibril array is more pronounced in wet than dry conditions, mainly related to fibril swelling. Differences leading to higher compressive strength between mineralised tissues seem not to depend on rehydration while the lack of kink bands supports the role of water as an elastic embedding influencing energy-absorption mechanisms. STATEMENT OF SIGNIFICANCE: Characterising structure-property-function relationships in hierarchical biological materials helps us to elucidate mechanisms that enable their unique properties. Experimental and computational methods can advance our understanding of their complex behaviour with the potential to inform bio-inspired material development. In this study, we close a gap for bone's fundamental mechanical building block at micro- and nanometre length scales. We establish a direct connection between experiments and simulations by coupling in situ synchrotron tests with a statistical model and quantify the behaviour of rehydrated single mineralised collagen fibres. Results suggest a high influence of hydration on structural interfaces, and the role of water as an elastic embedding by outlining important differences between wet and dry elasto-plastic properties of mineral nanocrystals, fibrils and fibres.

Nonlinear micro finite element models based on digital volume correlation measurements predict early microdamage in newly formed bone.

Bone regeneration in critical-sized defects is a clinical challenge, with biomaterials under constant development aiming at enhancing the natural bone healing process. The delivery of bone morphogenetic proteins (BMPs) in appropriate carriers represents a promising strategy for bone defect treatment but optimisation of the spatial-temporal release is still needed for the regeneration of bone with biological, structural, and mechanical properties comparable to the native tissue. Nonlinear micro finite element (µFE) models can address some of these challenges by providing a tool able to predict the biomechanical strength and microdamage onset in newly formed bone when subjected to physiological or supraphysiological loads. Yet, these models need to be validated against experimental data. In this study, experimental local displacements in newly formed bone induced by osteoinductive biomaterials subjected to in situ X-ray computed tomography compression in the apparent elastic regime and measured using digital volume correlation (DVC) were used to validate µFE models. Displacement predictions from homogeneous linear µFE models were highly correlated to DVC-measured local displacements, while tissue heterogeneity capturing mineralisation differences showed negligible effects. Nonlinear µFE models improved the correlation and showed that tissue microdamage occurs at low apparent strains. Microdamage seemed to occur next to large cavities or in biomaterial-induced thin trabeculae, independent of the mineralisation. While localisation of plastic strain accumulation was similar, the amount of damage accumulated in these locations was slightly higher when including material heterogeneity. These results demonstrate the ability of the nonlinear µFE model to capture local microdamage in newly formed bone tissue and can be exploited to improve the current understanding of healing bone and mechanical competence. This will ultimately aid the development of BMPs delivery systems for bone defect treatment able to regenerate bone with optimal biological, mechanical, and structural properties.

Multiscale mechanical consequences of ocean acidification for cold-water corals.

Ocean acidification is a threat to deep-sea corals and could lead to dramatic and rapid loss of the reef framework habitat they build. Weakening of structurally critical parts of the coral reef framework can lead to physical habitat collapse on an ecosystem scale, reducing the potential for biodiversity support. The mechanism underpinning crumbling and collapse of corals can be described via a combination of laboratory-scale experiments and mathematical and computational models. We synthesise data from electron back-scatter diffraction, micro-computed tomography, and micromechanical experiments, supplemented by molecular dynamics and continuum micromechanics simulations to predict failure of coral structures under increasing porosity and dissolution. Results reveal remarkable mechanical properties of the building material of cold-water coral skeletons of 462 MPa compressive strength and 45-67 GPa stiffness. This is 10 times stronger than concrete, twice as strong as ultrahigh performance fibre reinforced concrete, or nacre. Contrary to what would be expected, CWCs retain the strength of their skeletal building material despite a loss of its stiffness even when synthesised under future oceanic conditions. As this is on the material length-scale, it is independent of increasing porosity from exposure to corrosive water or bioerosion. Our models then illustrate how small increases in porosity lead to significantly increased risk of crumbling coral habitat. This new understanding, combined with projections of how seawater chemistry will change over the coming decades, will help support future conservation and management efforts of these vulnerable marine ecosystems by identifying which ecosystems are at risk and when they will be at risk, allowing assessment of the impact upon associated biodiversity.

Effect of patient inhalation profile and airway structure on drug deposition in image-based models with particle-particle interactions.

For many of the one billion sufferers of respiratory diseases worldwide, managing their disease with inhalers improves their ability to breathe. Poor disease management and rising pollution can trigger exacerbations that require urgent relief. Higher drug deposition in the throat instead of the lungs limits the impact on patient symptoms. To optimise delivery to the lung, patient-specific computational studies of aerosol inhalation can be used. However in many studies, inhalation modelling does not represent situations when the breathing is impaired, such as in recovery from an exacerbation, where the patient's inhalation is much faster and shorter. Here we compare differences in deposition of inhaler particles (10, 4 µm) in the airways of three patients. We aimed to evaluate deposition differences between healthy and impaired breathing with image-based healthy and diseased patient models. We found that the ratio of drug in the lower to upper lobes was 35% larger with a healthy inhalation. For smaller particles the upper airway deposition was similar in all patients, but local deposition hotspots differed in size, location and intensity. Our results identify that image-based airways must be used in respiratory modelling. Various inhalation profiles should be tested for optimal prediction of inhaler deposition.

An experimentally informed statistical elasto-plastic mineralised collagen fibre model at the micrometre and nanometre lengthscale.

Bone is an intriguingly complex material. It combines high strength, toughness and lightweight via an elaborate hierarchical structure. This structure results from a biologically driven self-assembly and self-organisation, and leads to different deformation mechanisms along the length scales. Characterising multiscale bone mechanics is fundamental to better understand these mechanisms including changes due to bone-related diseases. It also guides us in the design of new bio-inspired materials. A key-gap in understanding bone's behaviour exists for its fundamental mechanical unit, the mineralised collagen fibre, a composite of organic collagen molecules and inorganic mineral nanocrystals. Here, we report an experimentally informed statistical elasto-plastic model to explain the fibre behaviour including the nanoscale interplay and load transfer with its main mechanical components. We utilise data from synchrotron nanoscale imaging, and combined micropillar compression and synchrotron X-ray scattering to develop the model. We see that a 10-15% micro- and nanomechanical heterogeneity in mechanical properties is essential to promote the ductile microscale behaviour preventing an abrupt overall failure even when individual fibrils have failed. We see that mineral particles take up 45% of strain compared to collagen molecules while interfibrillar shearing seems to enable the ductile post-yield behaviour. Our results suggest that a change in mineralisation and fibril-to-matrix interaction leads to different mechanical properties among mineralised tissues. Our model operates at crystalline-, molecular- and continuum-levels and sheds light on the micro- and nanoscale deformation of fibril-matrix reinforced composites.

Heat impact during laser ablation extraction of mineralised tissue micropillars.

The underlying constraint of ultrashort pulsed laser ablation in both the clinical and micromachining setting is the uncertainty regarding the impact on the composition of material surrounding the ablated region. A heat model representing the laser-tissue interaction was implemented into a finite element suite to assess the cumulative temperature response of bone during ultrashort pulsed laser ablation. As an example, we focus on the extraction of mineralised collagen fibre micropillars. Laser induced heating can cause denaturation of the collagen, resulting in ultrastructural loss which could affect mechanical testing results. Laser parameters were taken from a used micropillar extraction protocol. The laser scanning pattern consisted of 4085 pulses, with a final radial pass being 22 [Formula: see text] away from the micropillar. The micropillar temperature was elevated to 70.58 [Formula: see text], remaining 79.42 [Formula: see text] lower than that of which we interpret as an onset for denaturation. We verified the results by means of Raman microscopy and Energy Dispersive X-ray Microanalysis and found the laser-material interaction had no effect on the collagen molecules or mineral nanocrystals that constitute the micropillars. We, thus, show that ultrashort pulsed laser ablation is a safe and viable tool to fabricate bone specimens for mechanical testing at the micro- and nanoscale and we provide a computational model to efficiently assess this.

Extrafibrillar matrix yield stress and failure envelopes for mineralised collagen fibril arrays.

Bone metabolic diseases such as osteoporosis constitute a major socio-economic challenge. A detailed understanding of the structure-property relationships of bone's underlying hierarchical levels has the potential to improve diagnosis and the ability to treat those diseases, especially with regards to the onset of failure. Therefore, elastic and yield properties of mineralised turkey leg tendon (MTLT), a mineralised tissue that is similar to bone but has a simpler multiscale structure, were investigated. Elastic properties were identified using a multiscale micromechanical model. The input parameters include constituent mechanical properties, volume fractions and inclusion aspect ratios and these were obtained from a wide variety of literature sources. The determined elastic properties were used to formulate micromechanically informed yield surfaces and to identify yield properties of MTLT at the nanometre length scale where failure is first reported to occur. This was done in conjunction with experimental results from the compression of micropillars extracted from individual mineralised collagen fibres. This data was then used to identify micromechanically informed failure envelopes. The shear yield stress of the extrafibrillar matrix, associated with interfibrillar sliding, was identified as 137.65 MPa. The ratio between tensile and compressive yield stress in the Drucker-Prager yield criterion was 0.65. For both criteria apparent yield stress of the mineralised collagen fibril decreased to 25.3-31.4% when varying fibril orientation from 0° to 90°. This study identified yield properties of extrafibrillar matrix using an aligned mineralised tissue. The ability to obtain yield stress data and unloading stiffness from micropillar compression tests of MTLT at the level of the mineralised collagen fibril array and downscaling these into the EM mitigates against possible errors associated with macroscopic stiffness predictions and proved to be an invaluable advantage compared to similar modelling approaches. Results may help to improve computational models that may then be used in pre-clinical testing or development of personalised treatment strategies.

Compositional and mechanical properties of growing cortical bone tissue: a study of the human fibula.

Human cortical bone contains two types of tissue: osteonal and interstitial tissue. Growing bone is not well-known in terms of its intrinsic material properties. To date, distinctions between the mechanical properties of osteonal and interstitial regions have not been investigated in juvenile bone and compared to adult bone in a combined dataset. In this work, cortical bone samples obtained from fibulae of 13 juveniles patients (4 to 18 years old) during corrective surgery and from 17 adult donors (50 to 95 years old) were analyzed. Microindentation was used to assess the mechanical properties of the extracellular matrix, quantitative microradiography was used to measure the degree of bone mineralization (DMB), and Fourier transform infrared microspectroscopy was used to evaluate the physicochemical modifications of bone composition (organic versus mineral matrix). Juvenile and adult osteonal and interstitial regions were analyzed for DMB, crystallinity, mineral to organic matrix ratio, mineral maturity, collagen maturity, carbonation, indentation modulus, indicators of yield strain and tissue ductility using a mixed model. We found that the intrinsic properties of the juvenile bone were not all inferior to those of the adult bone. Mechanical properties were also differently explained in juvenile and adult groups. The study shows that different intrinsic properties should be used in case of juvenile bone investigation.

Compressive behaviour of uniaxially aligned individual mineralised collagen fibres at the micro- and nanoscale.

The increasing incidence of osteoporotic bone fractures makes fracture risk prediction an important clinical challenge. Computational models can be utilised to facilitate such analyses. However, they critically depend on bone's underlying hierarchical material description. To understand bone's irreversible behaviour at the micro- and nanoscale, we developed an in situ testing protocol that allows us to directly relate the experimental data to the mechanical behaviour of individual mineralised collagen fibres and its main constitutive phases, the mineralised collagen fibrils and the mineral nanocrystals, by combining micropillar compression of single fibres with small angle X-ray scattering (SAXS) and X-ray diffraction (XRD). Failure modes were assessed by SEM. Strain ratios in the elastic region at fibre, fibril and mineral levels were found to be approximately 22:5:2 with strain ratios at the point of compressive strength of 0.23 ±â€¯0.11 for fibril-to-fibre and 0.07 ±â€¯0.01 for mineral-to-fibre levels. Mineral-to-fibre levels showed highest strain ratios around the apparent yield point, fibril-to-fibre around apparent strength. The mineralised collagen fibrils showed a delayed mechanical response, contrary to the mineral phase, which points towards preceding deformations of mineral nanocrystals in the extrafibrillar matrix. No damage was measured at the level of the mineralised collagen fibre which indicates an incomplete separation of the mineral and collagen, and an extrafibrillar interface failure. The formation of kink bands and the gradual recruitment of fibrils upon compressive loading presumably led to localised strains. Our results from a well-controlled fibrillar architecture provide valuable input for micromechanical models and computational non-linear bone strength analyses that may provide further insights for personalised diagnosis and treatment as well as bio-inspired implants for patients with bone diseases. STATEMENT OF SIGNIFICANCE: Musculoskeletal diseases such as osteoporosis, osteoarthritis or bone cancer significantly challenge health care systems and make fracture risk prediction and treatment optimisation important clinical goals. Computational methods such as finite element models have the potential to optimise analyses but highly depend on underlying material descriptions. We developed an in situ testing set-up to directly relate experimental data to the mechanical behaviour of bone's fundamental building block, the individual mineralised collagen fibre and its main constituents. Low multilevel strain ratios suggest high deformations in the extrafibrillar matrix and energy dissipation at the interfaces, the absence of damage indicates both an incomplete separation between mineral and collagen and an extrafibrillar interface failure. The formation of kink bands in the fibril-reinforced composite presumably led to localised strains. The deformation behaviour of a well-controlled fibrillar architecture provides valuable input for non-linear bone strength analyses.

"Peroperative estimation of bone quality and primary dental implant stability".

OBJECTIVES: Dental implants are widely used to restore function and appearance. It may be essential to choose the appropriate drilling protocol and implant design in order to optimise primary stability. This could be achieved based on an assessment of the implantation site with respect to bone quality and objective biomechanical descriptors such as stiffness and strength of the bone-implant system. The aim of this ex vivo study is to relate these descriptors with bone quality, with a pre-implantation indicator of implant stability: pilot-hole drilling force (Fdrilling), and with two post-implantation indicators: maximal implantation torque (Timplantation) and resonance frequency analysis (RFA). METHODS: Eighty trabecular bone specimens were cored from human vertebrae and bovine tibiae. Bone volume fraction (BV/TV), a representative for bone quality, was obtained through micro-computed tomography scans. Implants were kept in controlled laboratory conditions following standard surgical procedures. Forces and torques were recorded and RFA was assessed after implantation. Off-axis compression tests were conducted on the implants until failure. Implant stability was identified by stiffness and ultimate force (Fultimate). The relationships between BV/TV, Stiffness, Fultimate and Fdrilling, Timplantation, RFA were established. RESULTS: Fdrilling correlated well with BV/TV of the implantation site (r2 = 0.81), stiffness (r2 = 0.75) and Fultimate (r2 = 0.80). Timplantation correlated better with stiffness (r2 = 0.86) and Fultimate (r2 = 0.94) than RFA (r2 = 0.77 and r2 = 0.74, respectively). CONCLUSION: Our results indicate that BV/TV and bone-implant stability can be directly estimated by the force needed for the pilot drilling that occurs during the site preparation before implantation. Moreover, implantation torque outperforms RFA for evaluating the mechanical competence of the bone-implant system.

Comparative Analysis of Bone Structural Parameters Reveals Subchondral Cortical Plate Resorption and Increased Trabecular Bone Remodeling in Human Facet Joint Osteoarthritis.

Facet joint osteoarthritis is a prominent feature of degenerative spine disorders, highly prevalent in ageing populations, and considered a major cause for chronic lower back pain. Since there is no targeted pharmacological therapy, clinical management of disease includes analgesic or surgical treatment. The specific cellular, molecular, and structural changes underpinning facet joint osteoarthritis remain largely elusive. The aim of this study was to determine osteoarthritis-related structural alterations in cortical and trabecular subchondral bone compartments. To this end, we conducted comparative micro computed tomography analysis in healthy (n = 15) and osteoarthritic (n = 22) lumbar facet joints. In osteoarthritic joints, subchondral cortical plate thickness and porosity were significantly reduced. The trabecular compartment displayed a 42 percent increase in bone volume fraction due to an increase in trabecular number, but not trabecular thickness. Bone structural alterations were associated with radiological osteoarthritis severity, mildly age-dependent but not gender-dependent. There was a lack of association between structural parameters of cortical and trabecular compartments in healthy and osteoarthritic specimens. The specific structural alterations suggest elevated subchondral bone resorption and turnover as a potential treatment target in facet joint osteoarthritis.

A rate-independent continuum model for bone tissue with interaction of compressive and tensile micro-damage.

Low bone strength is a major risk factor for osteoporotic fractures and is only partially determined by clinical densitometry. Accumulated micro-damage induces residual strains, degrades elastic modulus and reduces bone strength independently of bone mineral density. Histologically, overloading of bone in compression and tension leads to distinct crack size, distribution and orientation which interact during combined loading scenarios. Statistics of rheological models can describe this process and reproduce experimental stress-strain curves with an unprecedented realism, but are computationally expensive and therefore difficult to generalize to 3D. Accordingly, the aim of this work is to formulate a continuum damage model that describes the key features of bone micro-damage, namely the accumulation of residual strains, the degradation of elastic modulus and the reduction of strength in compression, tension and especially in their sequential application. The promising qualitative agreement of the model with the experiments will motivate a generalization to 3D and allow the biomechanical investigation of bones and bone-implant systems subjected to cyclic overloading in tension and/or compression.

Nanoscale deformation mechanisms and yield properties of hydrated bone extracellular matrix.

Bone features a hierarchical architecture combining antagonistic properties like toughness and strength. In order to better understand the mechanisms leading to this advantageous combination, its postyield and failure behaviour was analyzed on the length scale of a single lamella. Micropillars were compressed to large strains under hydrated conditions to measure their anisotropic yield and post-yield behaviour. An increase in strength compared to the macroscale by a factor of 1.55 and a strong influence of hydration with a decrease by 60% in yield stress compared to vacuum conditions were observed. Post-compression transmission electron microscopic analysis revealed anisotropic deformation mechanisms. In axial pillars, where fibrils were oriented along the loading axis, kink bands were observed and shear cracks emerged at the interface of ordered and disordered regions. Micromechanical analysis of fibril kinking allowed an estimate of the extrafibrillar matrix shear strength to be made: 120±40MPa. When two opposing shear planes met a wedge was formed, splitting the micropillar axially in a mode 1 crack. Making use of an analytical solution, the mode 1 fracture toughness of bone extracellular matrix for splitting along the fibril direction was estimated to be 0.07MPam. This is 1-2 orders of magnitude smaller than on the macroscale, which may be explained by the absence of extrinsic toughening mechanisms. In transverse pillars, where fibrils were oriented perpendicular to the loading axis, cracks formed in regions where adverse fibril orientation reduced the local fracture resistance. This study underlines the importance of bone's hierarchical microstructure for its macroscopic strength and fracture resistance and the need to study structure-property relationships as well as failure mechanisms under hydrated conditions on all length scales. STATEMENT OF SIGNIFICANCE: Bone's hierarchical architecture combines toughness and strength. To understand the governing deformation mechanisms, its postyield behaviour was analyzed at the microscale. Micropillars were compressed in physiological solution; an increased strength compared to macroscale and an influence of hydration was found. Transmission electron microscopy revealed cracks forming in regions with adverse fibril orientation in transverse pillars. In axial pillars kink bands were observed and shear cracks emerged at the interface of ordered and disordered regions. It was estimated that bone's fracture toughness for splitting between fibrils is significantly smaller than on the macroscale. This study underlines the importance of bone's hierarchical microstructure and the need to study structure-property relationships on all length scales.

A new multiscale micromechanical model of vertebral trabecular bones.

A new three-dimensional (3D) multiscale micromechanical model has been suggested as adept at predicting the overall linear anisotropic mechanical properties of a vertebral trabecular bone (VTB) highly porous microstructure. A nested 3D modeling analysis framework spanning the multiscale nature of the VTB is presented herein. This hierarchical analysis framework employs the following micromechanical methods: the 3D parametric high-fidelity generalized method of cells (HFGMC) as well as the 3D sublaminate model. At the nanoscale level, the 3D HFGMC method is applied to obtain the effective elastic properties of a representative unit cell (RUC) representing the mineral collagen fibrils composite. Next at the submicron scale level, the 3D sublaminate model is used to generate the effective elastic properties of a repeated stack of multilayered lamellae demonstrating the nature of the trabeculae (bone-wall). Thirdly, at the micron scale level, the 3D HFGMC method is used again on a RUC of the highly porous VTB microstructure. The VTB-RUC geometries are taken from microcomputed tomography scans of VTB samples harvested from different vertebrae of human cadavers [Formula: see text]. The predicted anisotropic overall elastic properties for native VTBs are, then, examined as a function of age and sex. The predicted results of the VTBs longitudinal Young's modulus are compared to reported values found in the literature. The proposed 3D nested modeling analysis framework provides a good agreement with reported values of Young's modulus of single trabeculae as well as for VTB-RUC in the literature.

European Society of Biomechanics S.M. Perren Award 2016: A statistical damage model for bone tissue based on distinct compressive and tensile cracks.

Osteoporosis leads to bone fragility and represents a major health problem in our aging societies. Bone is a quasi-brittle hierarchical composite that exhibits damage with distinct crack morphologies in compression and tension when overloaded. A recent study reported the complex damage response of bovine compact bone under four different cyclic overloading experiments combining compression and tension. The aim of the present work is to propose a mechanistic model by which cracking bone accumulates residual strain and reduces elastic modulus in distinct compressive and tensile overloading modes. A simple rheological unit of bone with two types of cracks is formulated in the framework of continuum damage mechanics. A statistics of these rheological units is then assembled in parallel to compute the response of a macroscopic bone sample in which compressive and tensile cracks are opened, closed or propagated towards failure. The resulting constitutive model reproduces the key macroscopic features of bone tissue damage and delivers an excellent agreement with the four cyclic overloading experiments. The remarkable predictions of the model support the presence of (1) friction between the crack surfaces producing hystereses, (2) an incomplete closure of cracks leading to residual strains, (3) a bridging mechanism of collagen fibrils which failure reduces elastic modulus, and (4) two distinct classes of cracks where compressive cracks have a strong influence on tensile damage and tensile cracks have a limited impact on compressive damage. This work is expected to help improve our understanding of the bone damage mechanisms contributing to skeletal fragility and to foster a proper generalization of this damage behavior in 3D for computational analysis of bone and bone-implant systems.