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.

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.

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.