Response of thoracolumbar vertebral bodies to high rate compressive loading - biomed 2013.

Underbody blast (UBB) events created by improvised explosive devices are threats to warfighter survivability. High intensity blast waves emitted from these devices transfer large forces through vehicle structures to occupants, often resulting in injuries including debilitating spinal fractures. The vertical loading vector through the spine generates significant compressive forces at high strain rates. To better understand injury mechanisms and ultimately better protect vehicle occupants against UBB attacks, high-fidelity computational models are being developed to predict the human response to dynamic loading characteristic of these events. This effort details the results from a series of 23 high-rate compression tests on vertebral body specimen. A high-rate servo-hydraulic test system applied a range of compressive loading rates (.01 mm/s to 1238 mm/s) to vertebral bodies in the thoracolumbar region (T7-L5). The force-deflection curves generated indicate rate dependent sensitivity of vertebral stiffness, ultimate load and ultimate deflection. Specimen subjected to high-rate dynamic loading to failure experienced critical structural damage at 5.5% ± 2.1% deflection. Compared to quasi-static loading, vertebral bodies had greater stiffness, greater force to failure, and lower ultimate failure deflection at high rates. Post-failure, an average loss in height of 15% was observed, along with a mean reduction in strength of 48%. The resulting data from these tests will allow for enhanced biofidelity of computational models by characterizing the vertebral stiffness response and ultimate deflection at rates representative of UBB events.

Screening and characterization of microbial inhibitors against eukaryotic protein phosphatases (PP1 and PP2A).

AIM: To identify novel microbial inhibitors of protein phosphatase 1 (PP1). METHODS AND RESULTS: 750 actinomycetes and 408 microfungi were isolated from Sabah forest soils and screened for production of potential PP1 inhibitors using an in vivo screening system, in which candidate inhibitors were identified through mimicking the properties of PP1-deficient yeast cells. Acetone extracts of two fungi, H9318 (Penicillium) and H9978 (non-Penicillium) identified in this way showed inhibitory activity towards both mammalian PP1 and PP2A in an in vitro phosphatase assay, while extract from H7520 (Streptomyces) inhibited PP2A but not PP1. Consistently, using a drug-induced haploinsufficiency test, strains with either reduced PP1 or PP2A function were hypersensitive to H9318 and H9978 extracts whereas only the latter strain showed hypersensitivity to H7250 extract. H9318 extract was fractionated using RP-HPLC into two active peaks (S1 and S2). A yeast strain with reduced PP1 function showed hypersensitivity to fraction S2 whereas a strain with reduced PP2A function was hypersensitive to fraction S1. However, S1 and S2 inhibited both PP1 and PP2A activities to a similar extent. CONCLUSION: Three candidate PP inhibitors have been identified. SIGNIFICANCE AND IMPACT OF THE STUDY: Further development may generate useful research tools and ultimately therapeutic agents.

Evaluation of cervical laminectomy and laminoplasty. A longitudinal study in the goat model.

STUDY DESIGN: An evaluation of the longitudinal radiologic changes up to 6 months induced by multilevel laminectomy and laminoplasty and the biomechanical responses in the goat model, complemented by biomechanical studies of intact specimens. OBJECTIVES: To determine the long-term radiographic differences and biomechanical responses of laminectomy and laminoplasty in an in vivo animal model. SUMMARY OF BACKGROUND DATA: Previous clinical and laboratory studies have indicated that multilevel laminectomy can cause increased flexibility in the cervical spinal column. Although the potential for laminoplasty to resolve these changes has been suggested, other evaluations have not supported this contention. Clarification of this controversy with long-term in vivo studies has not been performed. METHODS: Ten adult goats were divided into two groups, one undergoing C3-C5 laminectomy and the other open-door laminoplasty. Lateral cervical spine radiographs were obtained at 4-week intervals for a 6-month period. After the goats were killed, biomechanical testing was performed using pure moment loading on the surgically treated specimens and on three intact (without surgery) cervical spinal columns. RESULTS: In the laminectomy preparations, the cervical curvature index was noted to decrease by 59% at 16 weeks (P < 0.028) and by 70% at 24 weeks (P < 0.002), whereas the decrease in laminoplasty was not significantly different. Biomechanical testing indicated a significantly increased sagittal-plane slack motion in the laminectomy group (55 degrees) compared with that in intact specimens (39 degrees), but no significant difference between the laminoplasty and intact groups with respect to this motion. Laminectomy was found to be significantly stiffer (36%) in flexion than in extension, whereas the contrary was true for laminoplasty (37%). CONCLUSIONS: Radiographic and biomechanical results in the goat model suggest that laminoplasty is superior to laminectomy in maintaining cervical alignment and preventing postoperative spinal deformities.

Effect of age and loading rate on human cervical spine injury threshold.

STUDY DESIGN: Statistical analysis of human cadaver cervical spine compression experiments. OBJECTIVES: To quantify the cervical spine compressive injury threshold as a function of the person's age, gender, and external loading rate. SUMMARY OF BACKGROUND DATA: Results of epidemiologic studies have indicated that most survivors of cervical spinal cord injury have spinal column fractures and dislocations that result from a compression or compression-flexion force vector. Cervical spinal column injury thresholds are dependent on many factors. Delineation of the injury thresholds according to age, gender, and loading rate is necessary to improve clinical assessments and prevention strategies. METHODS: Twenty-five human cadaver head-neck compression tests were included in the analysis. Two statistical models were used to quantify the effects of age, gender, and loading rate on the force required to induce failure in the cervical spine. A multiple linear regression model provided a direct equation that quantified the effects of the variables, and a proportional hazards model was used to quantify probability of injury with each factor. RESULTS: The regression model had a correlation coefficient of 0.87. There was an interactive effect between age and loading rate: Increasing age reduced the effect of loading rate and at approximately 82 years, loading rate had no effect. Men were consistently 600 N stronger than women. The 50% probability of failure for a 50-year-old man at a 4.5-m/sec loading rate was approximately 3.9 kN. Differences in probability curves followed the same trends as seen in the regression model. CONCLUSIONS: The effects of age on cervical spine injury threshold are coupled with the rate of loading experienced through the external force vector that causes the trauma. Assessment of injury mechanisms and thresholds should be based on the person's age, gender, and loading rate to determine treatment and prevent injuries.

Static and dynamic bending responses of the human cervical spine.

The quasi-static and dynamic bending responses of the human mid-lower cervical spine were determined using cadaver intervertebral joints fixed at the base to a six-axis load cell. Flexion bending moment was applied to the superior end of the specimen using an electrohydraulic piston. Each specimen was tested under three cycles of quasi-static load-unload and one high-speed dynamic load. A total of five specimens were included in this study. The maximum intervertebral rotation ranged from 11.0 to 15.4 deg for quasi-static tests and from 22.9 to 34.4 deg for dynamic tests. The resulting peak moments at the center of the intervertebral joint ranged from 3.8 to 6.9 Nm for quasi-static tests and from 14.0 to 31.8 Nm for dynamic tests. The quasi-static stiffness ranged from 0.80 to 1.35 Nm/deg with a mean of 1.03 Nm/deg (+/- 0.11 Nm/deg). The dynamic stiffness ranged from 1.08 to 2.00 Nm/deg with a mean of 1.50 Nm/deg (+/- 0.17 Nm/deg). The differences between the two stiffnesses were statistically significant (p < 0.01). Exponential functions were derived to describe the quasi-static and dynamic moment-rotation responses. These results provide input data for lumped-parameter models and validation data for finite element models to better investigate the biomechanics of the human cervical spine.

Finite element analysis of cervical facetectomy.

STUDY DESIGN: Moment-rotation responses and disc anulus stresses of intact and facetectomized C4-C6 cervical spinal units were analyzed using detailed, three-dimensional, finite element models. OBJECTIVES: To evaluate biomechanical effects of progressive unilateral and bilateral facet resections on cervical spine segmental mobility (external response) and disc anulus stress (internal response). SUMMARY OF BACKGROUND DATA: Experimental studies have demonstrated that facetectomy significantly increases segmental mobility of the cervical spine. The biomechanical effects of facetectomy on the internal response, however, have not been investigated. METHODS: Moment-rotation responses of C4 with respect to C6 and von Mises stress in the disc anulus were examined using finite element models of a 0% (intact), 25%, 50%, 75%, and 100% unilaterally and bilaterally facetectomized cervical spinal unit. The model simulations were conducted under the pure-moment loading of 1.8 Nm in flexion, extension, lateral bending, and axial torsion. The intact model also was validated experimentally under the same conditions. RESULTS: The moment-rotation responses of the intact unit were within the ranges of experimental data. Cervical rotations increased with the increased degree of facet resection. The greatest change occurred between 50% and 75% facet resections in bilateral facetectomy. Similar patterns were found for disc anulus stresses, but to a greater extent. The maximum increase in rotation (11%) and in anulus stress (30%) occurred in lateral bending. Torsion was the least affected loading mode. The effects of unilateral facetectomy were considerably less than those of 75% bilateral facetectomy. CONCLUSIONS: Facetectomy has a greater effect on anulus stress than on intervertebral joint stiffness. Significant increase in anulus stresses and segmental mobility may occur when bilateral facet resection exceeds 50%.

Finite element modeling of cervical laminectomy with graded facetectomy.

In this study, an anatomically accurate three-dimensional finite element model of the human lower cervical spine (C4-C6) was used to study the biomechanical effects of cervical laminectomy with and without graded facetectomy. The intact finite element model was validated under flexion, extension, lateral bending, and axial torsion load vectors of 1.8 Nm magnitude. The moment rotation response of the finite element model matched well with experimental data. The gross external (angular motion) and the internal (superior and inferior intervertebral disc stress) responses were delineated under the four physiological loading modes for these iatrogenic changes. Results indicated that laminectomy markedly altered the cervical angular motion and the disc stress under flexion compared with all other loading modes. Facetectomy increased the angular motion and the inferior disc stress notably under flexion but did not affect the adjacent superior disc stress. Facet resection of > 50% caused pronounced increases in angular rotation and intervertebral disc stresses. These findings suggest that the resection of more than one-half of this structure may require additional procedures to restore the strength of the cervical column. Although gross external motion response can be obtained by experimental studies, the internal stress response can only be determined using mathematical models such as the finite element model used in the present study. The accentuated changes in the disc stress compared with the changes in the external rotation may be clinically relevant because increased internal load/stress can result in disc degeneration. The present three-dimensional finite element model offers additional information to better understand the extrinsic and intrinsic responses of the iatrogenically altered cervical spine.

Finite element model of the human lower cervical spine: parametric analysis of the C4-C6 unit.

In this study, a three-dimensional finite element model of the human lower cervical spine (C4-C6) was constructed. The mathematical model was based on close-up CT scans from a young human cadaver. Cortical shell, cancellous core, endplates, and posterior elements including the lateral masses, pedicle, lamina, and transverse and spinous processes, and the intervertebral disks, were simulated. Using the material properties from literature, the 10,371-element model was exercised under an axial compressive mode of loading. The finite element model response agreed with literature. As a logical step, a parametric study was conducted by evaluating the biomechanical response secondary to changes in the elastic moduli of the intervertebral disk and the endplates. In the stress analysis, the minimum principal compressive stress was used for the cancellous core of the vertebral body and von Mises stress was used for the endplate component. The model output indicated that an increase in the elastic modulii of the disk resulted in an increase in the endplate stresses at all the three spinal levels. In addition, the inferior endplate of the middle vertebral body responded with the highest mean compressive stress followed by its superior counterpart. Furthermore, the middle vertebral body produced the highest compressive stresses compared to its counterparts. These findings appear to correlate with experimental results as well as common clinical experience wherein cervical fractures are induced due to external compressive forces. As a first step, this model will lead to more advanced simulations as additional data become available.

Finite element modeling of the C4-C6 cervical spine unit.

This study was conducted to develop a detailed, three-dimensional, anatomically accurate finite element model of the human cervical spine structure using close-up computed tomography scans and to validate against experimental data. The finite element model of the three vertebra segment C4-C6 unit consisted of 9178 solid elements and 1193 thin shell elements. The force-displacement response under axial compression correlated well with experimental data. Because of the inclusion of three levels in the spinal structure, it was possible to determine the internal mechanics of the various components at each level. The applicability of the model was illustrated by adopting appropriate material properties from literature. Results indicated that, the stresses in the anterior column were higher compared to the posterior column at the inferior level, while the opposite was found to be true at the superior level. The superior and inferior endplate stresses were higher in the middle vertebral body compared to the adjacent vertebrae. In addition, the stresses in the cancellous core of the middle, unconstrained vertebral body were higher. The present three-dimensional finite element model offers an additional facet to a better understanding of the biomechanics of the human cervical spine.

Finite element applications in human cervical spine modeling.

The authors present a comprehensive state-of-the-art and critical review of the finite element models of the human cervical spine. They also focused on the developments in model construction (geometry generation), constitutive law (material property) identification, loading and boundary condition details, and validation, the most important phase. A data base of available experimental sources is also provided, which can be used by the modeler for validating the finite element model. The potential developments in finite element modeling of the human cervical spine are discussed.

An experimental technique to induce and quantify complex cyclic forces to the lumbar spine.

The human spine is a complex, heterogeneous nonlinear and viscoelastic structure. In addition, in vivo loading is not uniaxial. Although many studies on the mechanical behavior of the spine under "pure" forces and single cycle load applications exist, little research is conducted with complex cyclic loads. In this study, we developed a technique to induce and quantify controlled complex physiological loads to the lumbar spinal column under cyclic (chronic) conditions. The methods described include specimen preparation and mounting to induce controlled complex loading (cyclic compression-flexion vector was chosen as an example), instrumentation, and biomechanical data to achieve the objectives. The results indicated that the specimen sustained the external load in a combined compression-flexion mechanism without considerable off-axis forces (lateral shears) and moments (lateral bending and torsion). By mounting the anchoring bolt in appropriate places (such as an anterolateral placement to induce compression-flexion-lateral bending), this technique can be used to apply and continuously quantify complex physiological acute or cyclic loads to describe the biomechanics of the spine. This procedure of inducing complex loads eliminates the difficulty in applying the principles of superposition, using the response from individual "pure" forces to account for the nonlinearity and viscoelasticity of the human lumbar spinal column.

Response of the ligamentous lumbar spine to cyclic bending loads.

The effect of a "pure" cyclic flexion bending moment on the three-dimensional load-displacement behavior of fresh ligamentous lumbar spine was investigated. The load-displacement behavior, for 11 L1-sacrum specimens, pre- and post-cyclic fatigue bending tests were quantified using a Selspot II system. A special fixture was designed to mount the specimen within the MTS system to administer "pure" cyclic flexion bending, under displacement control, for 5 hours. The testing was accomplished in a 100% humidity chamber at 0.5 Hz. The maximum cyclic bending moment, based on the literature dealing with loads experienced by the spine during activities involving lifting, was set at 3.0 Nm. An increase in motion of the order of 10% in the extension loading mode was observed. The increase in motion in other loading modes was not significant. In the extension loading mode, the increase in the anteroposterior displacement (retrodisplacement) in general was higher than the corresponding rotation component. The results suggest that the bending moment of low magnitude, usually experienced by the spine during activities of daily living, alone may not trigger the mechanical failure processes in the disc. The presence of high axial compressive loads on the disc seems to be the main contributing factor in this process. The presence of bending moments and axial twist along with axial compressive load may accelerate the unstable processes leading to low back pain.