Experimental Analysis of Fabricated Synthetic Midthoracic Paediatric Spine as Compared to the Porcine Spine Based on Range of Motion (ROM).

The present study is aimed at investigating the mechanical behaviour of fabricated synthetic midthoracic paediatric spine based on range of motion (ROM) as compared to porcine spine as the biological specimen. The main interest was to ensure that the fabricated synthetic model could mimic the biological specimen behaviour. The synthetic paediatric spine was designed as a 200% scaled-up model to fit into the Bionix Servohydraulic spine simulator. Biomechanical tests were conducted to measure the ROM and nonlinearity of sigmoidal curves at six degrees of freedom (DOF) with moments at ±4 Nm before the specimens failed. Results were compared with the porcine spine (biological specimen). The differences found between the lateral bending and axial rotation of synthetic paediatric spine as compared to the porcine spine were 18% and 3%, respectively, but was still within the range. Flexion extension of the synthetic spine is a bit stiff in comparison of porcine spine with 45% different. The ROM curves of the synthetic paediatric spine exhibited nonlinearities for all motions as the measurements of neutral zone (NZ) and elastic zone (EZ) stiffness were below "1." Therefore, it showed that the proposed synthetic paediatric spine behaved similarly to the biological specimen, particularly on ROM.

A combined experimental and computational study of mechanical properties after balloon kyphoplasty.

Vertebral compression fractures rank among the most frequent injuries to the musculoskeletal system, with more than 1 million fractures per annum worldwide. The past decade has seen a considerable increase in the utilisation of surgical procedures such as balloon kyphoplasty to treat these injuries. While many kyphoplasty studies have examined the risk of damage to adjacent vertebra after treatment, recent case reports have also emerged to indicate the potential for the treated vertebra itself to re-collapse after surgery. The following study presents a combined experimental and computational study of balloon kyphoplasty which aims to establish a methodology capable of evaluating these cases of vertebral re-collapse. Results from both the experimental tests and computational models showed significant increases in strength and stiffness after treatment, by factors ranging from 1.44 to 1.93, respectively. Fatigue tests on treated specimens showed a 37% drop in the rate of stiffness loss compared to the untreated baseline case. Further analysis of the computational models concluded that inhibited PMMA interdigitation at the interface during kyphoplasty could reverse improvements in strength and stiffness that could otherwise be gained by the treatment.

A Multiscale Finite Element Analysis of Balloon Kyphoplasty to Investigate the Risk of Bone-Cement Separation In Vivo.

BACKGROUND: During the past decade there has been a significant increase in the number of vertebral fractures being treated with the balloon kyphoplasty procedure. Although previous investigations have found kyphoplasty to be an effective treatment for reducing patient pain and lowering cement-leakage risk, there have been reports of vertebral recollapse following the procedure. These reports have indicated evidence of in vivo bone-cement separation leading to collapse of the treated vertebra. METHODS: The following study documents a multiscale analysis capable of evaluating the risk of bone-cement interface separation during lying, standing, and walking activities following balloon kyphoplasty. RESULTS: Results from the analysis found that instances of reduced cement interlock could initiate both tensile and shear separation of the interface region at up to 7 times the failure threshold during walking or up to 1.9 times the threshold during some cases for standing. Lying prone offered the best protection from interface failure in all cases, with a minimum safety factor of 2.95. CONCLUSIONS: The results of the multiscale analysis show it is essential for kyphoplasty simulations to take account of the micromechanical behavior of the bone-cement interface to be truly representative of the in vivo situation after the treatment. The results further illustrate the importance of ensuring adequate cement infiltration into the compacted bone periphery during kyphoplasty through a combination of new techniques, tools, and biomaterials in a multifaceted approach to solve this complex challenge.

Modelling permafrost thickness in Great Britain over glacial cycles.

Like other countries, the UK has opted for deep geological disposal for the long-term, safe management of higher-activity radioactive waste. However, a site and a geological environment have yet to be identified to host a geological disposal facility. In considering its long-term safety functionality, it is necessary to consider natural processes, such as permafrost development, that have the potential to alter the geological environment over the time-scale of glacial-interglacial cycles. We applied a numerical model to simulate the impact of long-term climatic variability on groundwater flow and permafrost dynamics in two contrasting geological settings in Great Britain: (i) higher strength rocks (HSR) overlain by higher permeability sandstones with a high topographic gradient (GS1); (ii) a mixed sedimentary sequence of high and low permeability rocks resting on igneous HSR with a very low topographic gradient (GS2). We evaluated the sensitivity of simulated permafrost thickness to a variety of climatic and subsurface conditions. Uncertainty in the scaling of the surface temperature time-series, 10-25 °C below present day temperature, has the largest impact on maximum permafrost thickness, PFmax, compared to other variables. However, considering plausible parameter ranges for UK settings, PFmax is up to twice as sensitive to changes in thermal conductivity and geothermal heat flux than to changes in porosity. Heat advection only affects modelled PFmax for high hydraulic conductivity rocks and if permafrost is considered to be relatively permeable. Whilst local differences in permafrost thickness of tens of meters, caused by variations in heat advection, are of minor importance over glacial-interglacial cycles, heat advection can be important in the development of taliks and the maintenance of a more active groundwater flow system. We conclude that it is likely to be important to simulate the effect of heat advection on coupled permafrost and groundwater flow systems in settings containing higher permeability lithological sequences.

Fatigue and damage of porcine pars interarticularis during asymmetric loading.

If the articular facets of the vertebra grow in an asymmetric manner, the developed bone geometry causes an asymmetry of loading. When the loading environment is altered by way of increased activity, the likelihood of acquiring a stress fracture may be increased. The combination of geometric asymmetry and increased activity is hypothesised to be the precursor to the stress fracture under investigation in this study, spondylolysis. This vertebral defect is an acquired fracture with 7% prevalence in the paediatric population. This value increases to 21% among athletes who participate in hyperextension sports. Tests were carried out on porcine lumbar vertebrae, on which the effect of facet angle asymmetry was simulated by offsetting the load laterally by 7mm from the mid-point. Strain in the vertebral laminae was recorded using six 3-element stacked rosette strain gauges placed bilaterally. Specimens were loaded cyclically at a rate of 2Hz. Fatigue cycles; strain, creep, secant modulus and hysteresis were measured. The principal conclusions of this paper are that differences in facet angle lead to an asymmetry of loading in the facet joints; this in turn leads to an initial increase in strain on the side with the more coronally orientated facet. The strain amplitude, which is the driving force for crack propagation, is greater on this side at all times up to fracture, the significance of this can be observed in the increased steady state creep rate (p = 0.036) and the increase in yielding and toughening mechanisms taking place, quantified by the force-displacement hysteresis (p = 0.026).

Strain distribution in the porcine lumbar laminae under asymmetric loading.

If the articular facets of the vertebra grow in an asymmetric manner, the developed geometry causes an asymmetry of loading. When the loading environment is altered by way of increased activity, the likelihood of acquiring a stress fracture may be increased. The combination of geometric asymmetry and increased activity is hypothesised to be the precursor to the stress fracture under investigation in this study, spondylolysis. This vertebral defect is an acquired fracture with 7% prevalence in the paediatric population. This value increases to 21% among athletes who participate in hyperextension sports. Tests were carried out on porcine lumbar vertebrae, on which the effect of facet angle asymmetry was simulated by offsetting the load laterally by 7 mm from the mid-point. The aim of the study is to investigate whether an increase in the coronal orientation of one facet leads to an increase in strain in the corresponding vertebral lamina. Strain in the laminae was recorded using six 3-element stacked rosette strain gauges placed bilaterally. Results show that a significant linear predictive relationship exists between load offset and average strain level in the vertebral laminae with p values of 0.006 and 0.045 for principal strains ε1 and ε2 on the right-hand side, and p-values of 0.009 and 0.001 for principal strains ε1 and ε2 on the left-hand side ( R2 all >0.9). This study concludes that facet angle asymmetry does lead to a difference in strain in the vertebral laminae. Change in principal strain as a result of facet asymmetry has a linear relationship and an asymmetry threshold exists beyond which compressive strain on the more coronally oriented facet can be increased by up to 15%.

Strong similarities in the creep and damage behaviour of a synthetic bone model compared to human trabecular bone under compressive cyclic loading.

Understanding the failure modes which instigate vertebral collapse requires the determination of trabecular bone fatigue properties, since many of these fractures are observed clinically without any preceding overload event. Alternatives to biological bone tissue for in-vitro fatigue studies are available in the form of commercially available open cell polyurethane foams. These test surrogates offer particular advantages compared to biological tissue such as a controllable architecture and greater uniformity. The present study provides a critical evaluation of these models as a surrogate to human trabecular bone tissue for the study of vertebral augmentation treatments such as balloon kyphoplasty. The results of this study show that while statistically significant differences were observed for the damage response of the two materials, both share a similar three phase modulus reduction over their life span with complete failure rapidly ensuing at damage levels above 30%. No significant differences were observed for creep accumulation properties, with greater than 50% of creep strains being accumulated during the first quarter of the life span for both materials. A significant power law relationship was identified between damage accumulation rate and cycles to failure for the synthetic bone model along with comparable microarchitectural features and a hierarchical composite structure consistent with biological bone. These findings illustrate that synthetic bone models offer potential as a surrogate for trabecular bone to an extent that warrants a full validation study to define boundaries of use which compliment traditional tests using biological bone.

Soluble factors from colonic epithelial cells contribute to gut homeostasis by modulating macrophage phenotype.

Intestinal macrophages originate from inflammatory blood monocytes which migrate to the intestine, where they differentiate into anti-inflammatory macrophages through a number of transitional stages. These macrophages typically remain hypo-responsive to commensal bacteria and food Ags in the intestine, yet also retain the ability to react to invading pathogens. In this study we examined the role of epithelial cells in inducing this intestinal macrophage phenotype. Using an in vitro system we showed that, in two-dimensional culture, epithelial cell-derived factors from a murine cell line, CMT-93, are sufficient to induce phenotypic changes in macrophages. Exposure of monocyte-derived macrophages, J774A.1, to soluble factors derived from epithelial cells, induced an altered phenotype similar to that of intestinal macrophages with decreased production of IL-12p40, IL-6 and IL-23 and expression of MHC ІІ and CD80 following TLR ligation. Furthermore, these conditioned macrophages showed enhanced phagocytic activity in parallel with low respiratory burst and NO production, similar to the response seen in intestinal macrophages. Our findings suggest a role for colonic epithelial cells in modulation of macrophage phenotype for maintenance of gut homeostasis. Further understanding of the cell interactions that maintain homeostasis in the gut could reveal novel therapeutic strategies to restore the balance in disease.

Conjugated linoleic acid suppresses dendritic cell activation and subsequent Th17 responses.

PUFAs (polyunsaturated fatty acids) can modify immune responses, so they may have potential therapeutic effects in inflammatory disorders. We previously demonstrated that the cis-9, trans-11 isomer of the PUFA conjugated linoleic acid (CLA) can modulate dendritic cell (DC) cytokine production. Since DCs play a central role in initiating inflammation by directing T helper (Th) cell differentiation, here we examined the effects of CLA on DC maturation and migration and the subsequent generation of Th cell responses. We examined the effect of CLA in vitro on the function of lipopolysaccharide (LPS)-activated bone marrow-derived DCs and ex vivo using cells from mice with high levels of CLA in their diet. We report that CLA inhibits DC migration and modulates TLR-induced production of key cytokines involved in Th cell differentiation both in vitro and in vivo. These changes were accompanied by a significant decrease in expression of MHCII, CD80 and CD86 on the DC surface. Exposure of DCs to CLA suppressed their ability to promote differentiation of naïve T cells into Th1 and/or Th17 cells in vitro and following their adoptive transfer in vivo. Furthermore, in a murine model of endotoxic shock, treatment with CLA suppressed LPS-induced induction of circulating IFN-γ, IL-12p40 and IL-1ß. This is the first study to demonstrate that exposure of antigen-presenting cells to CLA can modulate the subsequent Th cell response, and the findings may explain some of the beneficial effects of c9, t11-CLA in inflammatory diseases mediated by Th1 and Th17 cells.

A parametric finite element analysis of the compacted bone-cement interface following balloon kyphoplasty.

Treating fractures of the spine is a major challenge for the medical community with an estimated 1.4 million fractures per annum worldwide. While a considerable volume of study exists on the biomechanical implications of balloon kyphoplasty, which is used to treat these fractures, the influence of the compacted bone-cement region properties on stress distribution within the vertebral body remains unknown. The following article describes a novel method for modelling this compacted bone-cement region using a geometry-based approach in conjunction with the knowledge of the bone volume fractions for the native and compacted bone regions. Three variables for the compacted region were examined, as follows: (1) compacted thickness, (2) compacted region Young's modulus and (3) friction coefficient. Results from the model indicate that the properties of the compacted bone-cement region can affect stresses in the cortical bone and cement by up to +28% and -40%, respectively. These findings demonstrate the need for further investigation into the effects of the compacted bone-cement interface using computational and experimental methods on multi-segment models.