Electrochemically-Switched 2nd Order Non-Linear Optical Response in an Arylimido-Polyoxometalate with High Contrast and Cyclability.

Electrochemically switched 2nd order non-linear optical responses have been demonstrated for the first time in polyoxometalates (POMs), with an arylimido-derivative showing a leading combination of high on/off contrast (94 %), high visible transparency, and cyclability. Spectro-electrochemical and TD-DFT studies indicate that the switch-off results from weakened charge transfer (CT) character of the electronic transitions in the reduced state. This represents the first study of an imido-POM reduced state, and demonstrates the potential of POM hybrids as electrochemically activated molecular switches.

Center of mass and anatomical coordinate system definition for sheep head kinematics, with application to ovine models of traumatic brain injury.

Pathological outcomes of traumatic brain injury (TBI), including diffuse axonal injury, are influenced by the direction, magnitude, and duration of head acceleration during the injury exposure. Ovine models have been used to study injury mechanics and pathological outcomes of TBI. To accurately describe the kinematics of the head during an injury exposure, and better facilitate comparison with human head kinematics, anatomical coordinate systems (ACS) with an origin at the head or brain center of mass (CoM), and axes that align with the ovine Frankfort plane equivalent, are required. The aim of this study was to determine the mass properties of the sheep head and brain, and define an ACSvirtual for the head and brain, using anatomical landmarks on the skull with the aforementioned origins and orientation. Three-dimensional models of 10 merino sheep heads were constructed from computed tomography images, and the coordinates of the head and brain CoMs, relative to a previously reported sheep head coordinate system (ACSphysical ), were determined using the Hounsfield unit-mass density relationship. The ACSphysical origin was 34.8 ± 3.1 mm posterosuperior of the head CoM and 43.7 ± 1.7 anteroinferior of the brain CoM. Prominent internal anatomical landmarks were then used to define a new ACS (ACSvirtual ) with axes aligned with the Frankfort plane equivalent and an origin 10.4 ± 3.2 mm from the head CoM. The CoM and ACSvirtual defined in this study will increase the potential for comparison of head kinematics between ovine models and humans, in the context of TBI.

A Novel Nanostructured Surface on Titanium Implants Increases Osseointegration in a Sheep Model.

BACKGROUND: A nanostructured titanium surface that promotes antimicrobial activity and osseointegration would provide the opportunity to create medical implants that can prevent orthopaedic infection and improve bone integration. Although nanostructured surfaces can exhibit antimicrobial activity, it is not known whether these surfaces are safe and conducive to osseointegration. QUESTIONS/PURPOSES: Using a sheep animal model, we sought to determine whether the bony integration of medical-grade, titanium, porous-coated implants with a unique nanostructured surface modification (alkaline heat treatment [AHT]) previously shown to kill bacteria was better than that for a clinically accepted control surface of porous-coated titanium covered with hydroxyapatite (PCHA) after 12 weeks in vivo. The null hypothesis was that there would be no difference between implants with respect to the primary outcomes: interfacial shear strength and percent intersection surface (the percentage of implant surface with bone contact, as defined by a micro-CT protocol), and the secondary outcomes: stiffness, peak load, energy to failure, and micro-CT (bone volume/total volume [BV/TV], trabecular thickness [Tb.Th], and trabecular number [Tb.N]) and histomorphometric (bone-implant contact [BIC]) parameters. METHODS: Implants of each material (alkaline heat-treated and hydroxyapatite-coated titanium) were surgically inserted into femoral and tibial metaphyseal cancellous bone (16 per implant type; interference fit) and in tibial cortices at three diaphyseal locations (24 per implant type; line-to-line fit) in eight skeletally mature sheep. At 12 weeks postoperatively, bones were excised to assess osseointegration of AHT and PCHA implants via biomechanical push-through tests, micro-CT, and histomorphometry. Bone composition and remodeling patterns in adult sheep are similar to that of humans, and this model enables comparison of implants with ex vivo outcomes that are not permissible with humans. Comparisons of primary and secondary outcomes were undertaken with linear mixed-effects models that were developed for the cortical and cancellous groups separately and that included a random effect of animals, covariates to adjust for preoperative bodyweight, and implant location (left/right limb, femoral/tibial cancellous, cortical diaphyseal region, and medial/lateral cortex) as appropriate. Significance was set at an alpha of 0.05. RESULTS: The estimated marginal mean interfacial shear strength for cancellous bone, adjusted for covariates, was 1.6 MPa greater for AHT implants (9.3 MPa) than for PCHA implants (7.7 MPa) (95% CI 0.5 to 2.8; p = 0.006). Similarly, the estimated marginal mean interfacial shear strength for cortical bone, adjusted for covariates, was 6.6 MPa greater for AHT implants (25.5 MPa) than for PCHA implants (18.9 MPa) (95% CI 5.0 to 8.1; p < 0.001). No difference in the implant-bone percent intersection surface was detected for cancellous sites (cancellous AHT 55.1% and PCHA 58.7%; adjusted difference of estimated marginal mean -3.6% [95% CI -8.1% to 0.9%]; p = 0.11). In cortical bone, the estimated marginal mean percent intersection surface at the medial site, adjusted for covariates, was 11.8% higher for AHT implants (58.1%) than for PCHA (46.2% [95% CI 7.1% to 16.6%]; p < 0.001) and was not different at the lateral site (AHT 75.8% and PCHA 74.9%; adjusted difference of estimated marginal mean 0.9% [95% CI -3.8% to 5.7%]; p = 0.70). CONCLUSION: These data suggest there is stronger integration of bone on the AHT surface than on the PCHA surface at 12 weeks postimplantation in this sheep model. CLINICAL RELEVANCE: Given that the AHT implants formed a more robust interface with cortical and cancellous bone than the PCHA implants, a clinical noninferiority study using hip stems with identical geometries can now be performed to compare the same surfaces used in this study. The results of this preclinical study provide an ethical baseline to proceed with such a clinical study given the potential of the alkaline heat-treated surface to reduce periprosthetic joint infection and enhance implant osseointegration.

Tensile properties of human spinal dura mater and pericranium.

Autologous pericranium is a promising dural graft material. An optimal graft should exhibit similar mechanical properties to the native dura, but the mechanical properties of human pericranium have not been characterized, and studies of the biomechanical performance of human spinal dura are limited. The primary aim of this study was to measure the tensile structural and material properties of the pericranium, in the longitudinal and circumferential directions, and of the dura in each spinal region (cervical, thoracic and lumbar) and in three directions (longitudinal anterior and posterior, and circumferential). The secondary aim was to determine corresponding constitutive stress-strain equations using a one-term Ogden model. A total of 146 specimens were tested from 7 cadavers. Linear regression models assessed the effect of tissue type, region, and orientation on the structural and material properties. Pericranium was isotropic, while spinal dura was anisotropic with higher stiffness and strength in the longitudinal than the circumferential direction. Pericranium had lower strength and modulus than spinal dura across all regions in the longitudinal direction but was stronger and stiffer than dura in the circumferential direction. Spinal dura and pericranium had similar strain at peak force, toe, and yield, across all regions and directions. Human pericranium exhibits isotropic mechanical behavior that lies between that of the longitudinal and circumferential spinal dura. Further studies are required to determine if pericranium grafts behave like native dura under in vivo loading conditions. The Ogden parameters reported may be used for computational modeling of the central nervous system. Graphical abstract.

Investigating the Effect of Axial Compression and Distraction on Cervical Facet Mechanics During Supraphysiologic Anterior Shear.

Bilateral cervical facet dislocation (BFD) with facet fracture (Fx) often causes tetraplegia but is rarely recreated experimentally, possibly due to a lack of muscle replication. Intervertebral axial compression (due to muscle activation) or distraction (due to inertial loading), when combined with excessive anterior translation, may influence interfacet contact or separation and the subsequent production of BFD with or without Fx. This paper presents a methodology to produce C6/C7 BFD+Fx using anterior shear motion superimposed with 300 N compression or 2.5 mm distraction. The effect of these superimposed axial conditions on six-axis loads, and C6 inferior facet deflections and surface strains, was assessed. Twelve motion segments (70 ± 13 yr) achieved 2.19 mm of supraphysiologic anterior shear without embedding failure (supraphysiologic shear analysis point; SSP), and BFD+Fx was produced in all five specimens that reached 20 mm of shear. Linear mixed-effects models (α = 0.05) assessed the effect of axial condition. At the SSP, the compressed specimens experienced higher axial forces, facet shear strains, and sagittal facet deflections, compared to the distracted group. Facet fractures had similar radiographic appearance to those that are observed clinically, suggesting that intervertebral anterior shear motion contributes to BFD+Fx.

Lumbar spine loads are reduced for activities of daily living when using a braced arm-to-thigh technique.

PURPOSE: To evaluate the effect of the braced arm-to-thigh technique (BATT) (versus self-selected techniques) on three-dimensional trunk kinematics and spinal loads for three common activities of daily living (ADLs) simulated in the laboratory: weeding (gardening), reaching for an object in a low cupboard, and car egress using the two-legs out technique. METHODS: Ten young healthy males performed each task using a self-selected technique, and then using the BATT. The pulling action of weeding was simulated using a magnet placed on a steel plate. Cupboard and car egress tasks were simulated using custom apparatus representing the dimensions of a kitchen cabinet and a medium-sized Australian car, respectively. Three-dimensional trunk kinematics and L4/L5 spinal loads were estimated using the Lifting Full-Body OpenSim model and compared between techniques. Paired t-tests were used to compare peak values between methods (self-selected vs BATT). RESULTS: The BATT significantly reduced peak extension moments (13-51%), and both compression (27-45%) and shear forces (31-62%) at L4/L5, compared to self-selected techniques for all three tasks (p < 0.05). Lateral bending angles increased with the BATT for weeding and cupboard tasks, but these changes were expected as the BATT inherently introduces asymmetric trunk motion. CONCLUSION: The BATT substantially reduced L4/L5 extension moments, and L4/L5 compression and shear forces, compared to self-selected methods, for three ADLs, in a small cohort of ten young healthy males without prior history of back pain. These study findings can be used to inform safe procedures for these three ADLs, as the results are considered representative of a mature population.

Medial grasping sutures significantly improve load to failure of the rotator cuff suture bridge repair.

BACKGROUND: The suture bridge (SB) transosseous-equivalent rotator cuff repair reduces re-tear rates compared with single-row or other double-row constructs. However, failure rates continue to be high, especially in large and massive tears. The aim of this study was to assess the biomechanical performance of a new SB repair with use of a medial grasping suture compared with the traditional SB repair. METHODS: Seven matched pairs of sheep infraspinatus tendons were randomly assigned to either SB or suture bridge with grasping suture (SBGS) repair. Each construct was subjected to cyclic loading and then loaded until failure under displacement control in a materials testing machine. Footprint displacement, ultimate load to failure, and mode of failure were assessed. RESULTS: The rotator cuff footprint displacement was less during tensile loading with the addition of the medial grasping suture. The ultimate load to failure was significantly greater for the SBGS repair group than for the SB repair group (334.0 N vs 79.8 N). The mode of failure was the tendon pulling off the footprint in all cases (type 1 tear). There were no failures in which the tendon tore at the medial row of anchors, leaving part of the tendon still on the footprint (type 2 tear). CONCLUSION: The addition of a medial grasping suture significantly improved the ultimate load to failure and reduced the footprint displacement of the SB rotator cuff repair in a biomechanical model.

Kinematics, kinetics, and new insights from a contemporary analysis of the first experiments to produce cervical facet dislocations in the laboratory.

Background: The first experimental study to produce cervical facet dislocation (CFD) in cadaver specimens captured the vertebral motions and axial forces that are important for understanding the injury mechanics. However, these data were not reported in the original manuscript, nor been presented in the limited subsequent studies of experimental CFD. Therefore, the aim of this study was to re-examine the analog data from the first experimental study to determine the local and global spinal motions, and applied axial force, at and preceding CFD. Methods: In the original study, quasistatic axial loading was applied to 14 cervical spines by compressing them between two metal plates. Specimens were fixed caudally via a steel spindle positioned within the spinal canal and a bone pin through the inferior-most vertebral body. Global rotation of the occiput was restricted but its anterior translation was unconstrained. The instant of CFD was identified on sagittal cineradiograph films (N = 10), from which global and intervertebral kinematics were also calculated. Corresponding axial force data (N = 6) were extracted, and peak force and force at the instant of injury were determined. Results: CFD occurred in eight specimens, with an intervertebral flexion angle of 34.8 ± 5.6 degrees, and a 3.1 ± 1.9 mm increase in anterior translation, at the injured level. For seven specimens, CFD was produced at the level of transition from upper neck lordosis to lower neck kyphosis. Five specimens with force data underwent CFD at 545 ± 147 N, preceded by a peak axial force (755 ± 233 N) that appeared to coincide with either fracture or soft tissue failure. Conclusions: Re-examining this rich dataset has provided quantitative evidence that small axial compression forces, combined with anterior eccentricity and upper neck extension, can cause flexion and shear in the lower neck, leading to soft tissue rupture and CFD.

An Extended Neck Position is Likely to Produce Cervical Spine Injuries Through Buckling in Accidental Head-First Impacts During Rugby Tackling.

Catastrophic cervical spine injuries in rugby often occur during tackling. The underlying mechanisms leading to these injuries remain unclear, with neck hyperflexion and buckling both proposed as the causative factor in the injury prevention literature. The aim of this study was to evaluate the effect of pre-impact head-neck posture on intervertebral neck loads and motions during a head-first rugby tackle. Using a validated, subject-specific musculoskeletal model of a rugby player, and computer simulations driven by in vivo and in vitro data, we examined the dynamic response of the cervical spine under such impact conditions. The simulations demonstrated that the initial head-neck sagittal-plane posture affected intervertebral loads and kinematics, with an extended neck resulting in buckling and supraphysiologic intervertebral shear and flexion loads and motions, typical of bilateral facet dislocation injuries. In contrast, an initially flexed neck increased axial compression forces and flexion angles without exceeding intervertebral physiological limits. These findings provide objective evidence that can inform injury prevention strategies or rugby law changes to improve the safety of the game of rugby.

Evaluation of Apparatus and Protocols to Measure Human Passive Neck Stiffness and Range of Motion.

Understanding of human neck stiffness and range of motion (ROM) with minimal neck muscle activation ("passive") is important for clinical and bioengineering applications. The aim of this study was to develop, implement, and evaluate the reliability of methods for assessing passive-lying stiffness and ROM, in six head-neck rotation directions. Six participants completed two assessment sessions. To perform passive-lying tests, the participant's head and torso were strapped to a bending (flexion, extension, lateral bending) or a rotation (axial rotation) apparatus, and clinical bed, respectively. The head and neck were manually rotated by the researcher to the participant's maximum ROM, to assess passive-lying stiffness. Participant-initiated ("active") head ROM was also assessed in the apparatus, and seated. Various measures of apparatus functionality were assessed. ROM was similar for all assessment configurations in each motion direction except flexion. In each direction, passive stiffness generally increased throughout neck rotation. Within-session reliability for stiffness (ICC > 0.656) and ROM (ICC > 0.872) was acceptable, but between-session reliability was low for some motion directions, probably due to intrinsic participant factors, participant-apparatus interaction, and the relatively low participant number. Moment-angle corridors from both assessment sessions were similar, suggesting that with greater sample size, these methods may be suitable for estimating population-level corridors.

Neck stiffness and range of motion for young males and females.

Well characterised mechanical response of the normal head-neck complex during passive motion is important to inform and verify physical surrogate and computational models of the human neck, and to inform normal baseline for clinical assessments. For 10 male and 10 female participants aged 20 to 29, the range of motion (ROM) of the neck about three anatomical axes was evaluated in active-seated, passive-lying and active-lying configurations, and the neck stiffness was evaluated in passive-lying. Electromyographic signals from the agonist muscles, normalised to maximum voluntary contractions, were used to provide feedback during passive motions. The effect of sex and configuration on ROM, and the effect of sex on linear estimates of stiffness in three regions of the moment-angle curve, were assessed with linear mixed models and generalised linear models. There were no differences in male and female ROM across all motion directions and configurations. Flexion and axial rotation ROM were configuration dependent. The passive-lying moment-angle relationship was typically non-linear, with higher stiffness (slope) closer to end of ROM. When normalising the passive moment-angle curve to active lying ROM, passive stiffness was sex dependent only for lateral bending region 1 and 2. Aggregate moment-angle corridors were similar for males and females in flexion and extension, but exhibited a higher degree of variation in applied moment for males in lateral bending and axial rotation. These data provide the passive response of the neck to low rate bending and axial rotation angular displacement, which may be useful for computational and surrogate modelling of the human neck.

Facet deflection and strain are dependent on axial compression and distraction in C5-C7 spinal segments under constrained flexion.

Background: Facet fractures are frequently associated with clinically observed cervical facet dislocations (CFDs); however, to date there has only been one experimental study, using functional spinal units (FSUs), which has systematically produced CFD with concomitant facet fracture. The role of axial compression and distraction on the mechanical response of the cervical facets under intervertebral motions associated with CFD in FSUs has previously been shown. The same has not been demonstrated in multi-segment lower cervical spine specimens under flexion loading (postulated to be the local injury vector associated with CFD). Methods: This study investigated the mechanical response of the bilateral inferior C6 facets of thirteen C5-C7 specimens (67±13 yr, 6 male) during non-destructive constrained flexion, superimposed with each of five axial conditions: (1) 50 N compression (simulating weight of the head); (2-4) 300, 500, and 1000 N compression (simulating the spectrum of intervertebral compression resulting from neck muscle bracing prior to head-first impact and/or externally applied compressive forces); and, (5) 2 mm of C6/C7 distraction (simulating the intervertebral distraction present during inertial loading of the cervical spine by the weight of the head). Linear mixed-effects models (α = 0.05) assessed the effect of axial condition. Results: Increasing amounts of intervertebral compression superimposed on flexion rotations, resulted in increased facet surface strains (range of estimated mean difference relative to Neutral: maximum principal = 77 to 110 µÎµ, minimum principal = 126 to 293 µÎµ, maximum shear = 203 to 375 µÎµ) and angular deflection of the bilateral inferior C6 facets relative to the C6 vertebral body (range of estimated mean difference relative to Neutral = 0.59° to 1.47°). Conclusions: These findings suggest increased facet engagement and higher load transfer through the facet joint, and potentially a higher likelihood of facet fracture under the compressed axial conditions.

Bridge improvement work: maximising non-linear optical performance in polyoxometalate derivatives.

New phenyl and stilbene-bridged polyoxometalate (POM) charge-transfer chromophores with diphenylamino donor groups produce, respectively, the highest intrinsic and absolute quadratic hyperpolarisabilities measured for such species. The ß0,zzz obtained for the phenyl bridge - at 180 × 10-30 esu - is remarkable for a short conjugated system while changing to the stilbene (260 × 10-30 esu) produces a substantial increase in non-linearity for a minimal red-shift in the absorption profile. Together with TD-DFT calculations, the results show that maximising conjugation in the π-bridge is vital to high performance in such "POMophores".

Cerebrospinal fluid pressures resulting from experimental traumatic spinal cord injuries in a pig model.

Despite considerable effort over the last four decades, research has failed to translate into consistently effective treatment options for spinal cord injury (SCI). This is partly attributed to differences between the injury response of humans and rodent models. Some of this difference could be because the cerebrospinal fluid (CSF) layer of the human spine is relatively large, while that of the rodents is extremely thin. We sought to characterize the fluid impulse induced in the CSF by experimental SCIs of moderate and high human-like severity, and to compare this with previous studies in which fluid impulse has been associated with neural tissue injury. We used a new in vivo pig model (n = 6 per injury group, mean age 124.5 days, 20.9 kg) incorporating four miniature pressure transducers that were implanted in pairs in the subarachnoid space, cranial, and caudal to the injury at 30 mm and 100 mm. Tissue sparing was assessed with Eriochrome Cyanine and Neutral Red staining. The median peak pressures near the injury were 522.5 and 868.8 mmHg (range 96.7-1430.0) and far from the injury were 7.6 and 36.3 mmHg (range 3.8-83.7), for the moderate and high injury severities, respectively. Pressure impulse (mmHg.ms), apparent wave speed, and apparent attenuation factor were also evaluated. The data indicates that the fluid pressure wave may be sufficient to affect the severity and extent of primary tissue damage close to the injury site. However, the CSF pressure was close to normal physiologic values at 100 mm from the injury. The high injury severity animals had less tissue sparing than the moderate injury severity animals; this difference was statistically significant only within 1.6 mm of the epicenter. These results indicate that future research seeking to elucidate the mechanical origins of primary tissue damage in SCI should consider the effects of CSF. This pig model provides advantages for basic and preclinical SCI research due to its similarities to human scale, including the existence of a human-like CSF fluid layer.

Geometric and Inertial Properties of the Pig Head and Brain in an Anatomical Coordinate System.

Porcine models in injury biomechanics research often involve measuring head or brain kinematics. Translation of data from porcine models to other biomechanical models requires geometric and inertial properties of the pig head and brain, and a translationally relevant anatomical coordinate system (ACS). In this study, the head and brain mass, center of mass (CoM), and mass moments of inertia (MoI) were characterized, and an ACS was proposed for the pre-adolescent domestic pig. Density-calibrated computed tomography scans were obtained for the heads of eleven Large White × Landrace pigs (18-48 kg) and were segmented. An ACS with a porcine-equivalent Frankfort plane was defined using externally palpable landmarks (right/left frontal process of the zygomatic bone and zygomatic process of the frontal bone). The head and brain constituted 7.80 ± 0.79% and 0.33 ± 0.08% of the body mass, respectively. The head and brain CoMs were primarily ventral and caudal to the ACS origin, respectively. The mean head and brain principal MoI (in the ACS with origin at respective CoM) ranged from 61.7 to 109.7 kg cm2, and 0.2 to 0.6 kg cm2, respectively. These data may aid the comparison of head and brain kinematics/kinetics data and the translation between porcine and human injury models.

The Structural Response of the Human Head to a Vertex Impact.

In experimental models of cervical spine trauma caused by near-vertex head-first impact, a surrogate headform may be substituted for the cadaveric head. To inform headform design and to verify that such substitution is valid, the force-deformation response of the human head with boundary conditions relevant to cervical spine head-first impact models is required. There are currently no biomechanics data that characterize the force-deformation response of the isolated head supported at the occiput and compressed at the vertex by a flat impactor. The effect of impact velocity (1, 2 or 3 m/s) on the response of human heads (N = 22) subjected to vertex impacts, while supported by a rigid occipital mount, was investigated. 1 and 2 m/s impacts elicited force-deformation responses with two linear regions, while 3 m/s impacts resulted in a single linear region and skull base ring fractures. Peak force and stiffness increased from 1 to 2 and 3 m/s. Deformation at peak force and absorbed energy increased from 1 to 2 m/s, but decreased from 2 to 3 m/s. The data reported herein enhances the limited knowledge on the human head's response to a vertex impact, which may allow for validation of surrogate head models in this loading scenario.

Evaluating the effect of post-traumatic hypoxia on the development of axonal injury following traumatic brain injury in sheep.

Damage to the axonal white matter tracts within the brain is a key cause of neurological impairment and long-term disability following traumatic brain injury (TBI). Understanding how axonal injury develops following TBI requires gyrencephalic models that undergo shear strain and tissue deformation similar to the clinical situation and investigation of the effects of post-injury insults like hypoxia. The aim of this study was to determine the effect of post-traumatic hypoxia on axonal injury and inflammation in a sheep model of TBI. Fourteen male Merino sheep were allocated to receive a single TBI via a modified humane captive bolt animal stunner, or sham surgery, followed by either a 15 min period of hypoxia or maintenance of normoxia. Head kinematics were measured in injured animals. Brains were assessed for axonal damage, microglia and astrocyte accumulation and inflammatory cytokine expression at 4 hrs following injury. Early axonal injury was characterised by calpain activation, with significantly increased SNTF immunoreactivity, a proteolytic fragment of alpha-II spectrin, but not with impaired axonal transport, as measured by amyloid precursor protein (APP) immunoreactivity. Early axonal injury was associated with an increase in GFAP levels within the CSF, but not with increases in IBA1 or GFAP+ve cells, nor in levels of TNFα, IL1ß or IL6 within the cerebrospinal fluid or white matter. No additive effect of post-injury hypoxia was noted on axonal injury or inflammation. This study provides further support that axonal injury post-TBI is driven by different pathophysiological mechanisms, and detection requires specific markers targeting multiple injury mechanisms. Treatment may also need to be tailored for injury severity and timing post-injury to target the correct injury pathway.

Survival Model of Thoracic Contusion Spinal Cord Injury in the Domestic Pig.

Spinal cord injury (SCI) frequently results in motor, sensory, and autonomic dysfunction for which there is currently no cure. Recent pre-clinical and clinical research has led to promising advances in treatment; however, therapeutics indicating promise in rodents have not translated successfully in human trials, likely due, in part, to gross anatomical and physiological differences between the species. Therefore, large animal models of SCI may facilitate the study of secondary injury processes that are influenced by scale, and may assist the translation of potential therapeutic interventions. The aim of this study was to characterize two severities of thoracic contusion SCI in female domestic pigs, measuring motor function and spinal cord lesion characteristics, over 2 weeks post-SCI. A custom-instrumented weight-drop injury device was used to release a 50 g impactor from 10 cm (n = 3) or 20 cm (n = 7) onto the exposed dura, to induce a contusion at the T10 thoracic spinal level. Hind limb motor function was assessed at 8 and 13 days post-SCI using a 10-point scale. Volume and extent of lesion-associated signal hyperintensity in T2-weighted magnetic resonance (MR) images were assessed at 3, 7, and 14 days post-injury. Animals were transcardially perfused at 14 days post-SCI and spinal cord tissue was harvested for histological analysis. Bowel function was retained in all animals and transient urinary retention occurred in one animal after catheter removal. All animals displayed hind limb motor deficits. Animals in the 10-cm group demonstrated some stepping and weight-bearing and scored a median 2-3 points higher on the 10-point motor function scale at 8 and 13 days post-SCI, than did the 20-cm group. Histological lesion volume was 20% greater, and 30% less white matter was spared, in the 20-cm group than in the 10-cm group. The MR signal hyperintensity in the 20-cm injury group had a median cranial-caudal extent approximately 1.5 times greater than the 10-cm injury group at all three time-points, and median volumes 1.8, 2.5, and 4.5 times greater at day 3, 7, and 14 post-injury, respectively. Regional differences in axonal injury were observed between groups, with amyloid precursor protein immunoreactivity greatest in the 20-cm group in spinal cord sections adjacent to the injury epicenter. This study demonstrated graded injuries in a domestic pig strain, with outcome measures comparable to miniature pig models of contusion SCI. The model provides a vehicle for the study of SCI and potential treatments, particularly where miniature pig strains are not available and/or where small animal models are not appropriate for the research question.

Neurological scoring and gait kinematics to assess functional outcome in an ovine model of ischaemic stroke.

Background: Assessment of functional impairment following ischaemic stroke is essential to determine outcome and efficacy of intervention in both clinical patients and pre-clinical models. Although paradigms are well described for rodents, comparable methods for large animals, such as sheep, remain limited. This study aimed to develop methods to assess function in an ovine model of ischaemic stroke using composite neurological scoring and gait kinematics from motion capture. Methods: Merino sheep (n = 26) were anaesthetised and subjected to 2 hours middle cerebral artery occlusion. Animals underwent functional assessment at baseline (8-, 5-, and 1-day pre-stroke), and 3 days post-stroke. Neurological scoring was carried out to determine changes in neurological status. Ten infrared cameras measured the trajectories of 42 retro-reflective markers for calculation of gait kinematics. Magnetic resonance imaging (MRI) was performed at 3 days post-stroke to determine infarct volume. Intraclass Correlation Coefficients (ICC's) were used to assess the repeatability of neurological scoring and gait kinematics across baseline trials. The average of all baselines was used to compare changes in neurological scoring and kinematics at 3 days post-stroke. A principal component analysis (PCA) was performed to determine the relationship between neurological score, gait kinematics, and infarct volume post-stroke. Results: Neurological scoring was moderately repeatable across baseline trials (ICC > 0.50) and detected marked impairment post-stroke (p < 0.05). Baseline gait measures showed moderate to good repeatability for the majority of assessed variables (ICC > 0.50). Following stroke, kinematic measures indicative of stroke deficit were detected including an increase in stance and stride duration (p < 0.05). MRI demonstrated infarction involving the cortex and/or thalamus (median 2.7 cm3, IQR 1.4 to 11.9). PCA produced two components, although association between variables was inconclusive. Conclusion: This study developed repeatable methods to assess function in sheep using composite scoring and gait kinematics, allowing for the evaluation of deficit 3 days post-stroke. Despite utility of each method independently, there was poor association observed between gait kinematics, composite scoring, and infarct volume on PCA. This suggests that each of these measures has discreet utility for the assessment of stroke deficit, and that multimodal approaches are necessary to comprehensively characterise functional impairment.

Kinematic evaluation of one- and two-level Maverick lumbar total disc replacement caudal to a long thoracolumbar spinal fusion.

PURPOSE: Adjacent level degeneration that occurs above and/or below long fusion constructs is a documented clinical problem that is widely believed to be associated with the considerable change in stiffness caused by the fusion. Some researchers have suggested that early degeneration at spinal joints adjacent to a fusion could be treated by implanting total disc replacements at these levels. It is thought that further degeneration could be prevented through the disc replacement's design aims to reproduce normal disc heights, kinematics and tissue loading. For this reason, there is a clinical need to evaluate if a total disc replacement can maintain both the quantity of motion (i.e. range) and the quality of motion (i.e. center of rotation and coupling) at segments adjacent to a long spinal fusion. The purpose of this study was to experimentally evaluate range of motion (ROM-the intervertebral motion measured) and helical axis of motion (HAM) changes due to one- and two-level Maverick total disc replacement (TDR) adjacent to a long spinal fusion. METHODS: Seven spine specimens (T8-S1) were used in this study (66 ± 19 years old, 3F/4 M). A continuous pure moment of ±5.0 Nm was applied to the specimen in flexion-extension (FE), lateral bending (LB) and axial rotation (AR), with a compressive follower preload of 400 N. The 5.0 Nm data were analyzed to evaluate the operated segment biomechanics at the level of the disc replacements. The data were also analyzed at lower moments using a modified version of Panjabi's proposed "hybrid" method to evaluate adjacent segment kinematics (intervertebral motion at the segments adjacent to the fusion) under identical overall (T8-S1) specimen rotations. The motion of each vertebra was monitored with an optoelectronic camera system. The biomechanical test was completed for (1) the intact condition and repeated after each surgical technique was applied to the specimen, (2) capsulotomy at L4-L5 and L5-S1, (3) T8-L4 fusion and capsulotomy at L4-L5 and L5-S1, (4) Maverick at L4-L5, and (5) Maverick at L5-S1. The capsulotomy was performed to allow measurement of facet joint loads in a companion study. Paired t tests were used to determine if differences in the kinematic parameters measured were significant. Holm-Sidak corrections for multiple comparisons were applied where appropriate. RESULTS: Under the 5.0 Nm loads, L4-L5 ROMs tended to decrease in all directions following L4-L5 Maverick replacement (mean = 22 %, compared to the fused condition). Two-level Maverick implantation also tended to reduce L4-S1 ROM (mean 18, 7 and 31 % in FE, LB and AR, respectively, compared to the fused condition without TDR). Following TDR replacement, the HAM location tended to shift posteriorly in FE (at L5-S1), anteriorly in AR, and inferiorly in LB. However, although the above-mentioned trends were observed, neither one- nor two-level TDR replacement showed statistically significant ROM or HAM change in any of the three directions. At the identical T8-S1 posture identified by the modified hybrid analysis, the L4-L5 and L5-S1 levels underwent significant larger motions, relative to the overall specimen rotation, after fusion. In the hybrid analysis, there were no significant differences between the ROM after fusion with intact natural discs at L4-L5 and L5-S1 and the motions at those levels with one or two TDRs implanted. CONCLUSIONS: The present results demonstrated that one or two Maverick discs implanted subjacent to a long thoracolumbar fusion preserved considerable and intact-like ranges of motion and maintained motion patterns similar to the intact specimen, in this ex vivo study with applied pure moments and compressive follower preload. The hybrid analysis demonstrated that, after fusion, the TDR-implanted levels are required to undergo large rotations, relative to those necessary before fusion, in order to achieve the same motion between T8 and S1. Additional clinical and biomechanical research is necessary to determine if such a kinematic demand would be made on these levels clinically and the biomechanical performance of these implants if it were.