A review of foot finite element modelling for pressure ulcer prevention in bedrest: Current perspectives and future recommendations.

Pressure ulcers (PUs) are a major public health challenge, having a significant impact on healthcare service and patient quality of life. Computational biomechanical modelling has enhanced PU research by facilitating the investigation of pressure responses in subcutaneous tissue and skeletal muscle. Extensive work has been undertaken on PUs on patients in the seated posture, but research into heel ulcers has been relatively neglected. The aim of this review was to address the key challenges that exist in developing an effective FE foot model for PU prevention and the confusion surrounding the wide range of outputs reported. Nine FE foot studies investigating heel ulcers in bedrest were identified and reviewed. Six studies modelled the posterior part of the heel, two included the calf and foot, and one modelled the whole body. Due to the complexity of the foot anatomy, all studies involved simplification or assumptions regarding parts of the foot structure, boundary conditions and material parameters. Simulations aimed to understand better the stresses and strains exhibited in the heel soft tissues of the healthy foot. The biomechanical properties of soft tissue derived from experimental measurements are critical for developing a realistic model and consequently guiding clinical decisions. Yet, little to no validation was reported in each of the studies. If FE models are to address future research questions and clinical applications, then sound verification and validation of these models is required to ensure accurate conclusions and prediction of patient outcomes. Recommendations and considerations for future FE studies are therefore proposed.

Disrupted mitochondrial function in the Opa3L122P mouse model for Costeff Syndrome impairs skeletal integrity.

Mitochondrial dysfunction connects metabolic disturbance with numerous pathologies, but the significance of mitochondrial activity in bone remains unclear. We have, therefore, characterized the skeletal phenotype in the Opa3L122P mouse model for Costeff syndrome, in which a missense mutation of the mitochondrial membrane protein, Opa3, impairs mitochondrial activity resulting in visual and metabolic dysfunction. Although widely expressed in the developing normal mouse head, Opa3 expression was restricted after E14.5 to the retina, brain, teeth and mandibular bone. Opa3 was also expressed in adult tibiae, including at the trabecular surfaces and in cortical osteocytes, epiphyseal chondrocytes, marrow adipocytes and mesenchymal stem cell rosettes. Opa3L122P mice displayed craniofacial abnormalities, including undergrowth of the lower mandible, accompanied in some individuals by cranial asymmetry and incisor malocclusion. Opa3L122P mice showed an 8-fold elevation in tibial marrow adiposity, due largely to increased adipogenesis. In addition, femoral length and cortical diameter and wall thickness were reduced, the weakening of the calcified tissue and the geometric component of strength reducing overall cortical strength in Opa3L122P mice by 65%. In lumbar vertebrae reduced vertebral body area and wall thickness were accompanied by a proportionate reduction in marrow adiposity. Although the total biomechanical strength of lumbar vertebrae was reduced by 35%, the strength of the calcified tissue (σmax) was proportionate to a 38% increase in trabecular number. Thus, mitochondrial function is important for the development and maintenance of skeletal integrity, impaired bone growth and strength, particularly in limb bones, representing a significant new feature of the Costeff syndrome phenotype.

Biomechanical study: determining the optimum insertion angle for screw-in suture anchors-is deadman's angle correct?

PURPOSE: To assess the effect of the insertion angle and the angle of applied load on the pullout strength of screw-in suture anchors. METHODS: Screw-in metallic suture anchors were inserted into a 10-lb/cu ft synthetic cancellous bone block at 30°, 45°, 60°, and 90° to the surface. The suture pull angle was then varied in 30° increments between 0° and 180°. Five constructs were tested to failure (anchor pullout) for each combination of angles using a Zwick tensile testing machine (Zwick Roell, Ulm, Germany). RESULTS: There were a total of 25 combinations. The greatest pullout strength was seen with a suture anchor inserted at 90° to the bone block with a pull angle of 90° to the bone (mean, 306 N; standard deviation [SD], 9 N). The weakest pullout strength was seen with a suture anchor inserted at 30° with the angle of pull at 120° (i.e., opposite to the direction of insertion of the anchor) (mean, 97 N; SD, 11 N). A simulated deadman's angle of 45° with an angle of pull of 150° produced a pullout strength of 127 N (SD, 4 N). The pullout strengths for each insertion angle were greatest when the angle of pull was similar to the angle of insertion (P < .0001, repeated-measures analysis of variance). CONCLUSIONS: The angle of applied load to a suture anchor and the insertion angle significantly influence the biomechanical pullout strength of screw-in suture anchors. The insertion angle of the suture anchor should replicate the angle of applied load to ensure the optimum pullout strength. CLINICAL RELEVANCE: The screw-in anchor insertion angle and angle of applied load may have an influence on pullout strength.

Adhesive forces and surface properties of cold gas plasma treated UHMWPE.

Cold atmospheric plasma (CAP) treatment was used on ultra-high molecular weight polyethylene (UHMWPE), a common articulating counter material employed in hip and knee replacements. UHMWPE is a biocompatible polymer with low friction coefficient, yet does not have robust wear characteristics. CAP effectively cross-links the polymer chains of the UHMWPE improving wear performance (Perni et al., Acta Biomater. 8(3) (2012) 1357). In this work, interactions between CAP treated UHMWPE and spherical borosilicate sphere (representing model material for bone) were considered employing AFM technique. Adhesive forces increased, in the presence of PBS, after treatment with helium and helium/oxygen cold gas plasmas. Furthermore, a more hydrophilic surface of UHMWPE was observed after both treatments, determined through a reduction of up to a third in the contact angles of water. On the other hand, the asperity density also decreased by half, yet the asperity height had a three-fold decrease. This work shows that CAP treatment can be a very effective technique at enhancing the adhesion between bone and UHMWPE implant material as aided by the increased adhesion forces. Moreover, the hydrophilicity of the CAP treated UHMWPE can lead to proteins and cells adhesion to the surface of the implant stimulating osseointegration process.

Investigating mechanical and inflammatory pathological mechanisms in osteoarthritis using MSC-derived osteocyte-like cells in 3D.

Introduction: Changes to bone physiology play a central role in the development of osteoarthritis with the mechanosensing osteocyte releasing factors that drive disease progression. This study developed a humanised in vitro model to detect osteocyte responses to either interleukin-6, a driver of degeneration and bone remodelling in animal and human joint injury, or mechanical loading, to mimic osteoarthritis stimuli in joints. Methods: Human MSC cells (Y201) were differentiated in 3-dimensional type I collagen gels in osteogenic media and osteocyte phenotype assessed by RTqPCR and immunostaining. Gels were subjected to a single pathophysiological load or stimulated with interleukin-6 with unloaded or unstimulated cells as controls. RNA was extracted 1-hour post-load and assessed by RNAseq. Markers of pain, bone remodelling, and inflammation were quantified by RT-qPCR and ELISA. Results: Y201 cells embedded within 3D collagen gels assumed dendritic morphology and expressed mature osteocytes markers. Mechanical loading of the osteocyte model regulated 7564 genes (Padj p<0.05, 3026 down, 4538 up). 93% of the osteocyte transcriptome signature was expressed in the model with 38% of these genes mechanically regulated. Mechanically loaded osteocytes regulated 26% of gene ontology pathways linked to OA pain, 40% reflecting bone remodelling and 27% representing inflammation. Load regulated genes associated with osteopetrosis, osteoporosis and osteoarthritis. 42% of effector genes in a genome-wide association study meta-analysis were mechanically regulated by osteocytes with 10 genes representing potential druggable targets. Interleukin-6 stimulation of osteocytes at concentrations reported in human synovial fluids from patients with OA or following knee injury, regulated similar readouts to mechanical loading including markers of pain, bone remodelling, and inflammation. Discussion: We have developed a reproducible model of human osteocyte like cells that express >90% of the genes in the osteocyte transcriptome signature. Mechanical loading and inflammatory stimulation regulated genes and proteins implicated in osteoarthritis symptoms of pain as well as inflammation and degeneration underlying disease progression. Nearly half of the genes classified as 'effectors' in GWAS were mechanically regulated in this model. This model will be useful in identifying new mechanisms underlying bone and joint pathologies and testing drugs targeting those mechanisms.

In vivo strain measurements in the human buttock during sitting using MR-based digital volume correlation.

Advancements in systems for prevention and management of pressure ulcers require a more detailed understanding of the complex response of soft tissues to compressive loads. This study aimed at quantifying the progressive deformation of the buttock based on 3D measurements of soft tissue displacements from MR scans of 10 healthy subjects in a semi-recumbent position. Measurements were obtained using digital volume correlation (DVC) and released as a public dataset. A first parametric optimisation of the global registration step aimed at aligning skeletal elements showed acceptable values of Dice coefficient (around 80%). A second parametric optimisation on the deformable registration method showed errors of 0.99mm and 1.78mm against two simulated fields with magnitude 7.30±3.15mm and 19.37±9.58mm, respectively, generated with a finite element model of the buttock under sitting loads. Measurements allowed the quantification of the slide of the gluteus maximus away from the ischial tuberosity (IT, average 13.74 mm) that was only qualitatively identified in the literature, highlighting the importance of the ischial bursa in allowing sliding. Spatial evolution of the maximus shear strain on a path from the IT to the seating interface showed a peak of compression in the fat, close to the interface with the muscle. Obtained peak values were above the proposed damage threshold in the literature. Results in the study showed the complexity of the deformation of the soft tissues in the buttock and the need for further investigations aimed at isolating factors such as tissue geometry, duration and extent of load, sitting posture and tissue properties.

Distal humerus cortical strains following total elbow arthroplasty.

The aseptic loosening of total elbow replacements is a serious complication resulting in significant patient morbidity. It is thought to occur secondary to stress shielding of the distal humeral cortex by the stiff stem of the implant. Some total elbow prostheses incorporate an anterior flange intended to improve implant stability and peri-articular load transfer in an attempt to reduce this effect However, few studies have directly assessed the changes in cortical strains following total elbow arthroplasty or the biomechanical advantage of the anterior flange design. A regular and a long flange Coonrad-Morrey total elbow prosthesis were implanted into six Sawbone synthetic humeri. The constructs were subjected to physiological loads in axial compression (500 N), antero-posterior bending (50 N) and antero-posterior compression with condylar supports (300 N). Digital image correlation was used to measure the distal antero-lateral cortical strains and the results compared with those of whole Sawbones that had been tested in the same way. Significant stress shielding was demonstrated over the distal humeral cortex following prosthesis implantation during axial compression. In contrast, cortical strains increased following prosthesis implantation during antero-posterior compression with condylar supports. The increase in cortical strains following total elbow arthroplasty may help to maintain the integrity of the anterior cortex offering additional stability for implants with an anterior flange. These results are important for the development of future total elbow prosthesis designs and indicate that simulating the action of the forearm muscles is essential when evaluating changes in strain about the distal humerus in vitro.

Quantifying microcracks on fractured bone surfaces - Potential use in forensic anthropology.

Bone fracture surface morphology (FSM) can provide valuable information on the cause of failure in forensic and archaeological applications and it depends primarily on three factors, the loading conditions (like strain rate), the ambient conditions (wet or dry bone material) and the quality of bone material itself. The quality of bone material evidently changes in taphonomy as a result of the decomposition process and that in turn is expected to affect FSM. Porcine bones were fractured by a standardised impact during the course of soft tissue decomposition, at 28-day intervals, over 140 days (equivalent to 638 cooling degree days). Measurements of the associated microcracks on the fractured cortical bone surfaces indicated a progressive increase in mean length during decomposition from around 180 µm-375 µm. The morphology of these microcracks also altered, from multiple intersecting microcracks emanating from a central point at 0-28 cumulative cooling degree days, to longer linear cracks appearing to track lamellae as soft tissue decomposition progressed. The implications of these findings are that taphonomic changes of bone may offer the real possibility of distinguishing perimortem and taphonomic damage and also provide a new surrogate parameter for estimation of post-mortem interval (PMI) in forensics.

Fabrication of a positional brain shift phantom through the utilization of the frozen intermediate hydrogel state.

Synthetic models (phantoms) of the brain-skull system are useful tools for the study of surgical events that are otherwise difficult to study directly in humans. To date, very few studies can be found which replicate the full anatomical brain-skull system. Such models are required to study the more global mechanical events that can occur in neurosurgery, such as positional brain shift. Presented in this work is a novel workflow for the fabrication of a biofidelic brain-skull phantom which features a full hydrogel brain with fluid-filled ventricle/fissure spaces, elastomer dural septa and fluid-filled skull. Central to this workflow is the utilization of the frozen intermediate curing state of an established brain tissue surrogate, which allows for a novel moulding and skull installation approach that permits a much fuller recreation of the anatomy. The mechanical realism of the phantom was validated through indentation testing of the phantom's brain and simulation of the supine to prone brain shift event, while the geometric realism was validated through magnetic resonance imaging. The developed phantom captured a novel measurement of the supine to prone brain shift event with a magnitude that accurately reproduces that seen in the literature.

An analysis of the relationship between microneedle spacing, needle force and skin strain during the indentation phase prior to skin penetration.

Microneedle (MN) array patches present a promising new approach for the minimally invasive delivery of therapeutics and vaccines. However, ensuring reproducible insertion of MNs into the skin is challenging. The spacing and arrangement of MNs in an array are critical determinants of skin penetration and the mechanical integrity of the MNs. In this work, the finite element method was used to model the effect of MN spacing on needle reaction force and skin strain during the indentation phase prior to skin penetration. Spacings smaller than 2-3 mm (depending on variables, e.g., skin stretch) were found to significantly increase these parameters.

Fibroblast growth factor 2 and transforming growth factor ß1 induce precocious maturation of articular cartilage.

OBJECTIVE: We have discovered that a combination of fibroblast growth factor 2 and transforming growth factor ß1 induce profound morphologic changes in immature articular cartilage. The purpose of this study was to test the hypothesis that these changes represent accelerated postnatal maturation. METHODS: Histochemical and biochemical assays were used to confirm the nature of the morphologic changes that accompany growth factor stimulation of immature bovine articular cartilage explants in serum-free culture medium. Growth factor-induced apoptosis, cellular proliferation, and changes in the collagen network were also quantitatively analyzed. RESULTS: Growth factor stimulation resulted in rapid resorption from the basal aspect of immature cartilage explants that was simultaneously opposed by cellular proliferation from the apical aspect driven from a pool of chondroprogenitor cells we have previously described. Maturation-dependent changes in tissue stiffness, collagen crosslinking, and collagen fibril architecture as well as differentiation of the extracellular matrix into distinct pericellular, territorial, and interterritorial domains were all present in growth factor-stimulated cartilage samples and absent in control samples. CONCLUSION: Our data demonstrate that it is possible to significantly enhance the maturation of cartilage tissue using specific growth factor stimulation. This may have applications in transplantation therapy or in the treatment of diseased cartilage, through phenotype modulation of osteoarthritic chondrocytes in order to stimulate growth and maturation of cartilage repair tissue.

In vivo measurement of human brain material properties under quasi-static loading.

Computational modelling of the brain requires accurate representation of the tissues concerned. Mechanical testing has numerous challenges, in particular for low strain rates, like neurosurgery, where redistribution of fluid is biomechanically important. A finite-element (FE) model was generated in FEBio, incorporating a spring element/fluid-structure interaction representation of the pia-arachnoid complex (PAC). The model was loaded to represent gravity in prone and supine positions. Material parameter identification and sensitivity analysis were performed using statistical software, comparing the FE results to human in vivo measurements. Results for the brain Ogden parameters µ, α and k yielded values of 670 Pa, -19 and 148 kPa, supporting values reported in the literature. Values of the order of 1.2 MPa and 7.7 kPa were obtained for stiffness of the pia mater and out-of-plane tensile stiffness of the PAC, respectively. Positional brain shift was found to be non-rigid and largely driven by redistribution of fluid within the tissue. To the best of our knowledge, this is the first study using in vivo human data and gravitational loading in order to estimate the material properties of intracranial tissues. This model could now be applied to reduce the impact of positional brain shift in stereotactic neurosurgery.

A combined imaging, deformation and registration methodology for predicting respirator fitting.

N95/FFP3 respirators have been critical to protect healthcare workers and their patients from the transmission of COVID-19. However, these respirators are characterised by a limited range of size and geometry, which are often associated with fitting issues in particular sub-groups of gender and ethnicities. This study describes a novel methodology which combines magnetic resonance imaging (MRI) of a cohort of individuals (n = 8), with and without a respirator in-situ, and 3D registration algorithm which predicted the goodness of fit of the respirator. Sensitivity analysis was used to optimise a deformation value for the respirator-face interactions and corroborate with the soft tissue displacements estimated from the MRI images. An association between predicted respirator fitting and facial anthropometrics was then assessed for the cohort.

Full-field MRI measurements of in-vivo positional brain shift reveal the significance of intra-cranial geometry and head orientation for stereotactic surgery.

Positional brain shift (PBS), the sagging of the brain under the effect of gravity, is comparable in magnitude to the margin of error for the success of stereotactic interventions ([Formula: see text] 1 mm). This non-uniform shift due to slight differences in head orientation can lead to a significant discrepancy between the planned and the actual location of surgical targets. Accurate in-vivo measurements of this complex deformation are critical for the design and validation of an appropriate compensation to integrate into neuronavigational systems. PBS arising from prone-to-supine change of head orientation was measured with magnetic resonance imaging on 11 young adults. The full-field displacement was extracted on a voxel-basis via digital volume correlation and analysed in a standard reference space. Results showed the need for target-specific correction of surgical targets, as a significant displacement ranging from 0.52 to 0.77 mm was measured at surgically relevant structures. Strain analysis further revealed local variability in compressibility: anterior regions showed expansion (both volume and shape change), whereas posterior regions showed small compression, mostly dominated by shape change. Finally, analysis of correlation demonstrated the potential for further patient- and intervention-specific adjustments, as intra-cranial breadth and head tilt correlated with PBS reaching statistical significance.

Alternative radiopacifiers for polymethyl methacrylate bone cements: Silane-treated anatase titanium dioxide and yttria-stabilised zirconium dioxide.

Poly (methyl methacrylate) (PMMA) bone cement is widely used for anchoring joint arthroplasties. In cement brands approved for these procedures, micron-sized particles (usually barium sulphate, BaSO4) act as the radiopacifier. It has been postulated that these particles act as sites for crack initiation and subsequently cement fatigue. This study investigated whether alternative radiopacifiers, anatase titanium dioxide (TiO2) and yttria-stabilised zirconium dioxide (ZrO2), could improve the in vitro mechanical, fatigue crack propagation and biological properties of polymethyl methacrylate (PMMA) bone cement and whether their coating with a silane could further enhance cement performance. Cement samples containing 0, 5, 10, 15, 20 and 25%w/w TiO2 or ZrO2 and 10%w/w silane-treated TiO2 or ZrO2 were prepared and characterised in vitro in terms of radiopacity, compressive and bending strength, bending modulus, fatigue crack propagation, hydroxyapatite forming ability and MC3T3-E1 cell attachment and viability. Cement samples with greater than 10%w/w TiO2 and ZrO2 had a similar radiopacity to the control 10%w/w BaSO4 cement and commercial products. The addition of TiO2 and ZrO2 to bone cement reduced the bending strength and fracture toughness and increased fatigue crack propagation due to the formation of agglomerations and voids. Silane treating TiO2 reversed this effect, enhancing the dispersion and adhesion of particles to the PMMA matrix and resulted in improved mechanical properties and fatigue crack propagation resistance. Silane-treated TiO2 cements had increased nucleation of hydroxyapatite and MC3T3-E1 cell attachment in vitro, without significantly compromising cell viability. This research has demonstrated that 10%w/w silane-treated anatase TiO2 is a promising alternative radiopacifier for PMMA bone cement offering additional benefits over conventional BaSO4 radiopacifiers.

Effect of gap outside contact area on lubrication of metal-on-Metal total hip replacement.

Ball-in-socket metal on metal (MOM) contacts were analysed using the Abaqus Finite Element package to simulate dry contact between the acetabular cup and the femoral head. Different cup thicknesses of 4, 6, 8, and 10 mm were considered using a polyurethane foam block support system. Elastohydrodynamic lubrication (EHL) analyses were developed for the contacts using three different approaches to specify the contact. These were (i) A simple model based on the radii of relative curvature, (ii) An equivalent contact model developed so that its dry contact area and maximum pressure replicated the values obtained from the FE analysis, and (iii) A modified version of (ii) that also ensured equivalence of the gap shape outside the contact area. Published in vivo information for the hip joint contact forces over the walking cycle was used to specify the operating conditions for the EHL analysis. The analysis method was found to be effective for all points of the walking cycle for cases where the cup thickness exceeded 5 mm and modelling approach (ii) was identified as satisfactory. For a cup thickness of 4 mm, membrane action began to emerge in the FE analyses so that such contacts behaved in a different way.

Nonlinear scaling effects in the stiffness of soft cellular structures.

For cellular structures with uniform geometry, cell size and distribution, made from a neo-Hookean material, we demonstrate experimentally that large stretching causes nonlinear scaling effects governed by the microstructural architecture and the large strains at the cell level, which are not predicted by the linear elastic theory. For this purpose, three honeycomb-like structures with uniform square cells in stacked distribution were designed, where the number of cells varied, while the material volume and the ratio between the thickness and the length of the cell walls were fixed. These structures were manufactured from silicone rubber and tested under large uniaxial tension in a bespoke test fixture. Optical strain measurements were used to assess the deformation by capturing both the global displacements of the structure and the local deformations in the form of a strain map. The experimental results showed that, under sufficiently large strains, there was an increase in the stiffness of the structure when the same volume of material was arranged as many small cells compared to when it was organized as fewer larger cells. Finite element simulations confirmed our experimental findings. This study sheds light upon the nonlinear elastic responses of cellular structures in large-strain deformations, which cannot be captured within the linear elasticity framework.

Thermoneutrality improves skeletal impairment in adult Prader-Willi syndrome mice.

Human Prader-Willi syndrome (PWS) is characterised by impairments of multiple systems including the growth hormone (GH) axis and skeletal growth. To address our lack of knowledge of the influence of PWS on skeletal integrity in mice, we have characterised the endocrine and skeletal phenotype of the PWS-ICdel mouse model for "full" PWS and determined the impact of thermoneutrality. Tibial length, epiphyseal plate width and marrow adiposity were reduced by 6%, 18% and 79% in male PWS-ICdel mice, with osteoclast density being unaffected. Similar reductions in femoral length accompanied a 32% reduction in mid-diaphyseal cortical diameter. Distal femoral Tb.N was reduced by 62%, with individual trabeculae being less plate-like and the lattice being more fragmented (Tb.Pf increased by 63%). Cortical strength (Ultimate moment) was reduced by 26% as a result of reductions in calcified tissue strength and the geometric contribution. GH and prolactin contents in PWS-ICdel pituitaries were reduced in proportion to their smaller pituitary size, with circulating IGF-1 concentration reduced by 37-47%. Conversely, while pituitary LH content was halved, circulating gonadotropin concentrations were unaffected. Although longitudinal growth, marrow adiposity and femoral geometry were unaffected by thermoneutrality, strengthened calcified tissue reversed weakened cortex of PWS-ICdel femora. While underactivity of the GH-axis may be due to loss of Snord116 expression and impaired limb bone geometry and strength due to loss of Magel2 expression, comprehensive analysis of skeletal integrity in the single gene deletion models is required. Our data imply that thermoneutrality may ameliorate the elevated fracture risk associated with PWS.

An Analysis of Systematic Elemental Changes in Decomposing Bone.

The aim of this pilot study was to investigate compositional changes in bone during decomposition. Elemental concentrations of barium, calcium, iron, potassium, magnesium, zinc and phosphorus in porcine bone (as an experimental analog for human bone) were analyzed by inductively coupled plasma optical emission spectroscopy (ICP-OES). The samples were taken from porcine bone subjected to shallow burial and surface depositions at 28-day intervals for a period of 140 days. Results indicated that ICP-OES elemental profiling has potential to be developed as a forensic test for determining whether a bone sample originates from the early stages of soft tissue putrefaction. Significant changes in iron, sodium and potassium concentrations were found over 140 days. These elements are known to be primarily associated with proteins and/or tissue fluids within the bone. Changes in their respective concentrations may therefore be linked to dehydration over time and in turn may be indicative of time since deposition.