In vitro biomechanical testing of a micro external skeletal fixator

OBJECTIVE To biomechanically test the properties of three different Universal Micro External Fixator (UMEX™) configurations with regard to their use in very small animals (<5kg) and compare the UMEX system to the widely used IMEX External Skeletal Fixation (SK™) system in terms of stiffness, space needed for pin placement and weight. METHODS Three different UMEX configurations (type Ia, type Ib, and type II modified) and one SK configuration type Ia were used to stabilize Delrin plastic rods in a 1 cm fracture gap model. These constructs were tested in axial compression, craniocaudal bending, mediolateral bending, and torsion. Testing was conducted within the elastic range and mean stiffness in each mode was determined from the slope of the linear portion of the load-deformation curve. A Kruskal Wallis one-way analysis of variance on ranks test was utilized to assess differences between constructs (p <0.05). RESULTS The UMEX type II modified configuration was significantly stiffer than the other UMEX configurations and the SK type Ia, except in craniocaudal bending, where the SK type Ia configuration was stiffer than all UMEX constructs. The UMEX type Ia configuration was significantly the weakest of those frames. The UMEX constructs were lighter and smaller than the SK, thus facilitating closer pin placement. CONCLUSIONS Results supported previous reports concerning the superiority of more complex constructs regarding stiffness. The UMEX system appears to be a valid alternative for the treatment of long-bone fractures in very small animals.

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis

Summary Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

High resolution quantitative computed tomography-based assessment of trabecular microstructure and strength estimates by finite-element analysis of the spine, but not DXA, reflects vertebral fracture status in men with glucocorticoid-induced osteoporosis

High-resolution quantitative computed tomography (HRQCT)-based analysis of spinal bone density and microstructure, finite element analysis (FEA), and DXA were used to investigate the vertebral bone status of men with glucocorticoid-induced osteoporosis (GIO). DXA of L1–L3 and total hip, QCT of L1–L3, and HRQCT of T12 were available for 73 men (54.6±14.0years) with GIO. Prevalent vertebral fracture status was evaluated on radiographs using a semi-quantitative (SQ) score (normal=0 to severe fracture=3), and the spinal deformity index (SDI) score (sum of SQ scores of T4 to L4 vertebrae). Thirty-one (42.4%) subjects had prevalent vertebral fractures. Cortical BMD (Ct.BMD) and thickness (Ct.Th), trabecular BMD (Tb.BMD), apparent trabecular bone volume fraction (app.BV/TV), and apparent trabecular separation (app.Tb.Sp) were analyzed by HRQCT. Stiffness and strength of T12 were computed by HRQCT-based nonlinear FEA for axial compression, anterior bending and axial torsion. In logistic regressions adjusted for age, glucocorticoid dose and osteoporosis treatment, Tb.BMD was most closely associated with vertebral fracture status (standardized odds ratio [sOR]: Tb.BMD T12: 4.05 [95% CI: 1.8–9.0], Tb.BMD L1–L3: 3.95 [1.8–8.9]). Strength divided by cross-sectional area for axial compression showed the most significant association with spine fracture status among FEA variables (2.56 [1.29–5.07]). SDI was best predicted by a microstructural model using Ct.Th and app.Tb.Sp (r2=0.57, p<0.001). Spinal or hip DXA measurements did not show significant associations with fracture status or severity. In this cross-sectional study of males with GIO, QCT, HRQCT-based measurements and FEA variables were superior to DXA in discriminating between patients of differing prevalent vertebral fracture status. A microstructural model combining aspects of cortical and trabecular bone reflected fracture severity most accurately.

Measuring the bending of asymmetric planar EAP structures

The geometric characterization of low-voltage dielectric electro-active polymer (EAP) structures, comprised of nanometer thickness but areas of square centimeters, for applications such as artificial sphincters requires methods with nanometer precision. Direct optical detection is usually restricted to sub-micrometer resolution because of the wavelength of the light applied. Therefore, we propose to take advantage of the cantilever bending system with optical readout revealing a sub-micrometer resolution at the deflection of the free end. It is demonstrated that this approach allows us to detect bending of rather conventional planar asymmetric, dielectric EAP-structures applying voltages well below 10 V. For this purpose, we built 100 μm-thin silicone films between 50 nm-thin silver layers on a 25 μm-thin polyetheretherketone (PEEK) substrate. The increase of the applied voltage in steps of 50 V until 1 kV resulted in a cantilever bending that exhibits only in restricted ranges the expected square dependence. The mean laser beam displacement on the detector corresponded to 6 nm per volt. The apparatus will therefore become a powerful mean to analyze and thereby improve low-voltage dielectric EAP-structures to realize nanometer-thin layers for stack actuators to be incorporated into artificial sphincter systems for treating severe urinary and fecal incontinence.

Minimally Invasive Intraoperative Stiffness Measurement of Lumbar Spinal Motion Segments

OBJECTIVE: To test a new tiny-tipped intraoperative diagnostic tool that was designed to provide the surgeon with reliable stiffness data on the motion segment during microdiscectomy. A decrease in stiffness after nuclectomy and a measurable influence of muscle tension were assumed. If the influence of muscle tension on the motion segment could at least be ruled out, there should be no difference with regard to stiffness between women and men. If these criteria are met, this new intraoperative diagnostic tool could be used in further studies for objective decision-making regarding additional stabilization systems after microdiscectomy. METHODS: After evaluation of the influence of muscle relaxation during in vivo measurements with a spinal spreader between the spinous processes, 21 motion segments were investigated in 21 patients. Using a standardized protocol, including quantified muscle relaxation, spinal stiffness was measured before laminotomy and after nuclectomy. RESULTS: The decrease in stiffness after microdiscectomy was highly significant. There were no statistically significant differences between men and women. The average stiffness value before discectomy was 33.7 N/mm, and it decreased to 25.6 N/mm after discectomy. The average decrease in stiffness was 8.1 N/mm (24%). CONCLUSION: In the moderately degenerated spine, stiffness decreases significantly after microdiscectomy. Control for muscle relaxation is essential when measuring in vivo spinal stiffness. The new spinal spreader was found to provide reliable data. This spreader could be used in further studies for objective decision-making about additional stabilization systems after microdiscectomy.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Specimen specific parameter identification of ovine lumbar intervertebral discs: On the influence of fibre-matrix and fibre-fibre shear interactions.

Numerical models of the intervertebral disc, which address mechanical questions commonly make use of the difference in water content between annulus and nucleus, and thus fluid and solid parts are separated. Despite this simplification, models remain complex due to the anisotropy and nonlinearity of the annulus and regional variations of the collagen fibre density. Additionally, it has been shown that cross-links make a large contribution to the stiffness of the annulus. Because of this complex composite structure, it is difficult to reproduce several sets of experimental data with one single set of material parameters. This study addresses the question to which extent the ultrastructure of the intervertebral disc should be modelled so that its moment-angle behaviour can be adequately described. Therefore, a hyperelastic constitutive law, based on continuum mechanical principles was derived, which does not only consider the anisotropy from the collagen fibres, but also interactions among the fibres and between the fibres and the ground substance. Eight ovine lumbar intervertebral discs were tested on a custom made spinal loading simulator in flexion/extension, lateral bending and axial rotation. Specimen-specific geometrical models were generated using CT images and T2 maps to distinguish between annulus fibrosus and nucleus pulposus. For the identification of the material parameters the annulus fibrosus was described with two scenarios: with and without fibre-matrix and fibre-fibre interactions. Both scenarios showed a similar behaviour on a load displacement level. Comparing model predictions to the experimental data, the mean RMS of all specimens and all load cases was 0.54±0.15° without the interaction and 0.54±0.19° when the fibre-matrix and fibre-fibre interactions were included. However, due to the increased stiffness when cross-links effects were included, this scenario showed more physiological stress-strain relations in uniaxial and biaxial stress states. Thus, the present study suggests that fibre-matrix and fibre-fibre interactions should be considered in the constitutive law when the model addresses questions concerning the stress field of the annulus fibrosus.

Axial suspension test to assess pre-operative spinal flexibility in patients with adolescent idiopathic scoliosis.

INTRODUCTION An accurate description of the biomechanical behavior of the spine is crucial for the planning of scoliotic surgical correction as well as for the understanding of degenerative spine disorders. The current clinical assessments of spinal mechanics such as side-bending or fulcrum-bending tests rely on the displacement of the spine observed during motion of the patient. Since these tests focused solely on the spinal kinematics without considering mechanical loads, no quantification of the mechanical flexibility of the spine can be provided. METHODS A spinal suspension test (SST) has been developed to simultaneously monitor the force applied on the spine and the induced vertebral displacements. The system relies on cervical elevation of the patient and orthogonal radiographic images are used to measure the position of the vertebras. The system has been used to quantify the spinal flexibility on five AIS patients. RESULTS Based on the SST, the overall spinal flexibility varied between 0.3 °/Nm for the patient with the stiffer curve and 2 °/Nm for the less rigid curve. A linear correlation was observed between the overall spinal flexibility and the change in Cobb angle. In addition, the segmental flexibility calculated for five segments around the apex was 0.13 ± 0.07 °/Nm, which is similar to intra-operative stiffness measurements previously published. CONCLUSIONS In summary, the SST seems suitable to provide pre-operative information on the complex functional behavior and stiffness of spinal segments under physiological loading conditions. Such tools will become increasingly important in the future due to the ever-increasing complexity of the surgical instrumentation and procedures.

Bone Volume Fraction and Fabric Anisotropy Are Better Determinants of Trabecular Bone Stiffness than Other Morphological Variables

As our population ages, more individuals suffer from osteoporosis. This disease leads to impaired trabecular architecture and increased fracture risk. It is essential to understand how morphological and mechanical properties of the cancellous bone are related. Morphologyelasticity relationships based on bone volume fraction (BV/TV) and fabric anisotropy explain up to 98% of the variation in elastic properties. Yet, other morphological variables such as individual trabeculae segmentation (ITS) and trabecular bone score (TBS) could improve the stiffness predictions. A total of 743 micro-computed tomography reconstructions of cubic trabecular bone samples extracted from femur, radius, vertebrae and iliac crest were analysed. Their morphology was assessed via 25 variables and their stiffness tensor (inline image) was computed from six independent load cases using micro finite element analyses. Variance inflation factors were calculated to evaluate collinearity between morphological variables and decide upon their inclusion in morphology-elasticity relationships. The statistically admissible morphological variables were included in a multi-linear regression modelling the dependent variable inline image. The contribution of each independent variable was evaluated (ANOVA). Our results show that BV/TV is the best determinant of inline image (inline image=0.889), especially in combination with fabric (inline image=0.968). Including the other independent predictors hardly affected the amount of variance explained by the model (inline image=0.975). Across all anatomical sites, BV/TV explained 87% of the variance of the bone elastic properties. Fabric further described 10% of the bone stiffness, but the improvement in variance explanation by adding other independent factors was marginal (<1%). These findings confirm that BV/TV and fabric are the best determinants of trabecular bone stiffness and show, against common belief, that other morphological variables do not bring any further contribution. These overall conclusions remain to be confirmed for specific bone diseases and post-elastic properties.

Image-based biomechanical assessment of vertebral body and intervertebral disc in the human lumbar spine

Life expectancy continuously increases but our society faces age-related conditions. Among musculoskeletal diseases, osteoporosis associated with risk of vertebral fracture and degenerative intervertebral disc (IVD) are painful pathologies responsible for tremendous healthcare costs. Hence, reliable diagnostic tools are necessary to plan a treatment or follow up its efficacy. Yet, radiographic and MRI techniques, respectively clinical standards for evaluation of bone strength and IVD degeneration, are unspecific and not objective. Increasingly used in biomedical engineering, CT-based finite element (FE) models constitute the state-of-art for vertebral strength prediction. However, as non-invasive biomechanical evaluation and personalised FE models of the IVD are not available, rigid boundary conditions (BCs) are applied on the FE models to avoid uncertainties of disc degeneration that might bias the predictions. Moreover, considering the impact of low back pain, the biomechanical status of the IVD is needed as a criterion for early disc degeneration. Thus, the first FE study focuses on two rigid BCs applied on the vertebral bodies during compression test of cadaver vertebral bodies, vertebral sections and PMMA embedding. The second FE study highlights the large influence of the intervertebral disc’s compliance on the vertebral strength, damage distribution and its initiation. The third study introduces a new protocol for normalisation of the IVD stiffness in compression, torsion and bending using MRI-based data to account for its morphology. In the last study, a new criterion (Otsu threshold) for disc degeneration based on quantitative MRI data (axial T2 map) is proposed. The results show that vertebral strength and damage distribution computed with rigid BCs are identical. Yet, large discrepancies in strength and damage localisation were observed when the vertebral bodies were loaded via IVDs. The normalisation protocol attenuated the effect of geometry on the IVD stiffnesses without complete suppression. Finally, the Otsu threshold computed in the posterior part of annulus fibrosus was related to the disc biomechanics and meet objectivity and simplicity required for a clinical application. In conclusion, the stiffness normalisation protocol necessary for consistent IVD comparisons and the relation found between degeneration, mechanical response of the IVD and Otsu threshold lead the way for non-invasive evaluation biomechanical status of the IVD. As the FE prediction of vertebral strength is largely influenced by the IVD conditions, this data could also improve the future FE models of osteoporotic vertebra.

Increased ambulatory arterial stiffness index in obese children.

OBJECTIVE Altered arterial stiffness is a recognized risk factor of poor cardiovascular health. Ambulatory arterial stiffness index (AASI, defined as one minus the regression slope of diastolic on systolic blood pressure values derived from a 24 h arterial blood pressure monitoring, ABPM) is an upcoming and readily available marker of arterial stiffness. Our hypothesis was that AASI is increased in obese children compared to age- and gender matched healthy subjects. METHODS AASI was calculated from ABPM in 101 obese children (BMI ≥ 1.88 SDS according to age- and sex-specific BMI charts), 45% girls, median BMI SDS 2.8 (interquartile range (IQR) 2.5-3.4), median age 11.5 years (9.1-13.4) and compared with an age and gender matched healthy control group of 71 subjects with median BMI SDS 0.0 (-0.8-0.5). Multivariate regression analysis was applied to identify significant independent factors explaining AASI variability in this population. RESULTS AASI was significantly higher in obese children compared to controls (0.388 (0.254-0.499) versus 0.190 (0.070-0.320), p < 0.0001), but blood pressure values were similar. In a multivariate analysis including obese children only, AASI was independently predicted by 24-h systolic blood pressure SDS (p = 0.012); in a multivariate analysis including obese children and controls BMI SDS and pulse pressure independently influenced AASI (p < 0.001). CONCLUSIONS This study shows that AASI, a surrogate marker of arterial stiffness, is increased in obese children. AASI seems to be influenced by BMI and pulse pressure independently of systolic and diastolic blood pressure values, suggesting that other factors are involved in increased arterial stiffness in obese children.

Arterial stiffness is increased in asthmatic children.

UNLABELLED Altered arterial stiffness is a recognized risk factor of poor cardiovascular health. Chronic inflammation may increase arterial stiffness. We tested whether arterial stiffness is increased children with asthma, a chronic disease characterized by fluctuating airway and systemic inflammation. Arterial stiffness, expressed as carotid-femoral pulse wave velocity (PWVcf), was measured in 37 mild-to-moderate asthmatic children: 11 girls, median (range) age 11.1 years (6-15). PWVcf in asthma was compared to PWVcf in 65 healthy controls matched for age, height, and gender previously studied in Germany and was correlated with airway inflammation and obstruction. PWVcf was higher in asthmatic children compared to controls: PWVcf median (interquartile range) was 4.7 m/s (4.5-4.9) vs. 4.3 m/s (4.1-4.7), p < 0.0001. In asthmatic children, PWVcf was inversely associated (r (2) = 0.20, p = 0.004) with forced expiratory volume in 1 s (FEV1). This association remained significant after adjusting for possible confounders including body mass index, blood pressure, steroid use, and FeNO. CONCLUSION Arterial stiffness is increased in children with mild-to-moderate asthma. The association between impaired lung function and increased arterial stiffness suggests that severity of disease translates into detrimental effects on the cardiovascular system.

Mechanical restoration and failure analyses of a hydrogel and scaffold composite strategy for annulus fibrosus repair

Unrepaired defects in the annulus fibrosus of intervertebral disks are associated with degeneration and persistent back pain. A clinical need exists for a disk repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disk height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disk biomechanics with low herniation risk, suggesting further evaluation for disk repair may be warranted. Statement of significance Lower back pain is the leading cause of global disability and commonly caused by defects and failure of intervertebral disk tissues resulting in herniation and compression of adjacent nerves. Annulus fibrosus repair materials and techniques have not been successful due to the challenging mechanical and chemical microenvironment and the needs to restore biomechanical behaviors and promote healing with negligible herniation risk while being delivered during surgical procedures. This work addressed this challenging biomaterial and clinical problem using novel materials including an adhesive hydrogel, a scaffold capable of cell delivery, and a membrane to prevent herniation. Composite repair strategies were evaluated and optimized in quantitative three-part study that rigorously evaluated disk repair and provided a framework for evaluating alternate repair techniques.

Biomechanical evaluation of different angle-stable locking plate systems for mandibular surgery

PURPOSE To compare the initial stability and stability after fatigue of three different locking systems (Synthes(®), Stryker(®) and Medartis(®)) for mandibular fixation and reconstruction. METHOD Standard mandible locking plates with identical profile height (1,5 mm), comparable length and screws with identical diameter (2,0 mm) were used. Plates were fixed with six screws according a preparation protocol. Four point bending tests were then performed using artificial bone material to compare their initial stability and failure limit under realistic loading conditions. Loading of the plates was performed using of a servo hydraulic driven testing machine. The stiffness of the implant/bone construct was calculated using a linear regression on the experimental data included in a range of applied moment between 2 Nm and 6 Nm. RESULTS No statistical difference in the elastic stiffness was visible between the three types of plate. However, differences were observed between the systems concerning the maximal load supported. The Stryker and Synthes systems were able to support a significantly higher moment. CONCLUSION For clinical application all systems show good and reliable results. Practical aspects such as handling, possible angulation of screw fixation, possibility of screw/plate removal, etc. may favour one or the other plating system.