A Cross-Sectional Study of Bone Nanomechanics in Hip Fracture and Aging.

Bone mechanics is well understood at every length scale except the nano-level. We aimed to investigate the relationship between bone nanoscale and tissue-level mechanics experimentally. We tested two hypotheses: (1) nanoscale strains were lower in hip fracture patients versus controls, and (2) nanoscale mineral and fibril strains were inversely correlated with aging and fracture. A cross-sectional sample of trabecular bone sections was prepared from the proximal femora of two human donor groups (aged 44-94 years): an aging non-fracture control group (n = 17) and a hip-fracture group (n = 20). Tissue, fibril, and mineral strain were measured simultaneously using synchrotron X-ray diffraction during tensile load to failure, then compared between groups using unpaired t-tests and correlated with age using Pearson's correlation. Controls exhibited significantly greater peak tissue, mineral, and fibril strains than the hip fracture (all p < 0.05). Age was associated with a decrease in peak tissue (p = 0.099) and mineral (p = 0.004) strain, but not fibril strain (p = 0.260). Overall, hip fracture and aging were associated with changes in the nanoscale strain that are reflected at the tissue level. Data must be interpreted within the limitations of the observational cross-sectional study design, so we propose two new hypotheses on the importance of nanomechanics. (1) Hip fracture risk is increased by low tissue strain, which can be caused by low collagen or mineral strain. (2) Age-related loss of tissue strain is dependent on the loss of mineral but not fibril strain. Novel insights into bone nano- and tissue-level mechanics could provide a platform for the development of bone health diagnostics and interventions based on failure mechanisms from the nanoscale up.

3D models of chondrocytes within biomimetic scaffolds: Effects of cell deformation from loading regimens.

BACKGROUND: Mechanical conditioning has been widely used to attempt to enhance chondrocyte metabolism for the evolution of functionally competent cartilage. However, although upregulation of proteoglycans have been reported through the application of uniaxial compression, minimal collagen has been produced. The study is designed to examine whether alternative loading regimens, equivalent to physiological conditions, involving shear in addition to compression can enhance collagen production. METHODS: Finite element models were developed to determine how the local chondrocyte environments within agarose constructs were influenced by a range of static and dynamic loading regimens. 3-D poro-viscoelastic models were validated against experimental data. In particular, these models were used to characterise chondrocyte deformation in compression with and without shear superimposed, with special reference to the formation of pericellular matrix around the cells. FINDINGS: The models of the hydrogel constructs under stress relaxation and dynamic cyclic compression conditions were highly correlated with the experimental data. The cell deformation (y/z) in the constructs was greatest in the centre of the constructs, increasing with magnitude of compression up to 25%. The superposition of shear however did not produce significant additional changes in deformation, with the presence of PCM reducing the chondrocyte deformation. INTERPRETATION: The use of FE models can prove important in the definition of appropriate, optimised mechanical conditioning regimens for the synthesis and organisation of mature extra cellular matrix by chondrocyte-seeded constructs. They will also provide insight into the mechanisms relating cell deformation to mechanotransduction pathways, thereby progressing the development of functionally competent tissue engineered cartilage.

Fabella prevalence rate increases over 150 years, and rates of other sesamoid bones remain constant: a systematic review.

The fabella is a sesamoid bone located behind the lateral femoral condyle. It is common in non-human mammals, but the prevalence rates in humans vary from 3 to 87%. Here, we calculate the prevalence of the fabella in a Korean population and investigate possible temporal shifts in prevalence rate. A total of 52.83% of our individuals and 44.34% of our knees had fabellae detectable by computed tomography scanning. Men and women were equally likely to have a fabella, and bilateral cases (67.86%) were more common than unilateral ones (32.14%). Fabella presence was not correlated with height or age, although our sample did not include skeletally immature individuals. Our systematic review yielded 58 studies on fabella prevalence rate from 1875-2018 which met our inclusion criteria, one of which was an outlier. Intriguingly, a Bayesian mixed effects generalized linear model revealed a temporal shift in prevalence rates, with the median prevalence rate in 2000 (31.00%) being ~ 3.5 times higher than that in 1900 (7.64%). In all four countries with studies before and after 1960, higher rates were always found after 1960. Using data from two other systematic reviews, we found no increase in prevalence rates of 10 other sesamoid bones in the human body, indicating that the increase in fabella prevalence rate is unique. Fabella presence/absence is due to a combination of genetic and environmental factors: as the prevalence rates of other sesamoid bones have not changed in the last 100 years, we postulate the increase in fabella prevalence rate is due to an environmental factor. Namely, the global increase in human height and weight (due to improved nutrition) may have increased human tibial length and muscle mass. Increases in tibial length could lead to a larger moment arm acting on the knee and on the tendons crossing it. Coupled with the increased force from a larger gastrocnemius, this could produce the mechanical stimuli necessary to initiate fabella formation and/or ossification.

The contribution of the glenoid labrum to glenohumeral stability under physiological joint loading using finite element analysis.

The labrum contributes to passive glenohumeral joint stability. Cadaveric studies have demonstrated that this has position and load dependency, which has not been quantified under physiological loads. This study aims to validate subject-specific finite element (FE) models against in vitro measurements of joint stability and to utilise the FE models to predict joint stability under physiological loads. The predicted stability values were within ± one standard deviation of experimental data and the FE models showed a reduction in stability of 10-15% with high, physiological, loads. The developed regression equations provide the first representation of passive glenohumeral stability and will aid surgical decision-making.

Design and validation of an in vitro loading system for the combined application of cyclic compression and shear to 3D chondrocytes-seeded agarose constructs.

Physiological loading is essential for the maintenance of articular cartilage by regulating tissue remodelling, in the form of both catabolic and anabolic processes. To promote the development of tissue engineered cartilage which closely matches the long term functionality of native tissue, bioreactors have been developed to provide a combination of loading modalities, which reflect the nature of normal physiological loads. This study describes the design and validation of an in vitro mechanical system for the controlled application of bi-axial loading regimes to chondrocyte-seeded agarose constructs. The computer-controlled system incorporates a robust gripping system, which ensures the delivery of precise values of cyclic compressive and shear strain to 3D cell-seeded constructs. Sample prototypes were designed, optimised using finite element analysis and validated performing compressive and shear fatigue mechanical tests. The horizontal and vertical displacements within the bioreactor are precisely controlled by a dedicated programme that can be easily implemented. The synchronisation of the orthogonal displacements was shown to be accurate and reproducible. Constructs were successfully loaded with a combined compressive and shear loading regimen at 1 Hz for up to 48 h with no appreciable loss of cell viability or mechanical integrity. These features along with the demonstrated high consistency make the system ideally suitable for a systematic investigation of the response of chondrocytes to a complex physiologically relevant deformation profile.