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.Sacha Cavelier, Ryan D. Quarrington, Claire F. Jone

The Effect of Axial Compression and Distraction on Cervical Facet Cartilage Apposition During Shear and Bending Motions

During cervical spine trauma, complex intervertebral motions can cause a reduction in facet joint cartilage apposition area (CAA), leading to cervical facet dislocation (CFD). Intervertebral compression and distraction likely alter the magnitude and location of CAA, and may influence the risk of facet fracture. The aim of this study was to investigate facet joint CAA resulting from intervertebral distraction (2.5 mm) or compression (50, 300 N) superimposed on shear and bending motions. Intervertebral and facet joint kinematics were applied to multi rigid-body kinematic models of twelve C6/C7 motion segments (70 ± 13 year, nine male) with specimen-specific cartilage profiles. CAA was qualitatively and quantitatively compared between distraction and compression conditions for each motion; linear mixed-effects models (a = 0.05) were applied. Distraction significantly decreased CAA throughout all motions, compared to the compressed conditions (p<0.001), and shifted the apposition region towards the facet tip. These observations were consistent bilaterally for both asymmetric and symmetric motions. The results indicate that axial neck loads, which are altered by muscle activation and head loading, influences facet apposition. Investigating CAA in longer cervical spine segments subjected to quasistatic or dynamic loading may provide insight into dislocation and fracture mechanisms.Ryan D. Quarrington, Darcy W. Thompson-Bagsshaw and Claire F. Jone

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

OnlinePublIn 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.Darcy W. Thompson, Bagshaw, Ryan D. Quarrington, Andrew M. Dwyer, Nigel R. Jones, Claire F. Jone

Prevention of adhesions post-abdominal surgery: Assessing the safety and efficacy of Chitogel with Deferiprone in a rat model

Introduction: Adhesions are often considered to be an inevitable consequence of abdominal and pelvic surgery, jeopardizing the medium and long-term success of these procedures. Numerous strategies have been tested to reduce adhesion formation, however, to date, no surgical or medical therapeutic approaches have been successful in its prevention. This study demonstrates the safety and efficacy of Chitogel with Deferiprone and/or antibacterial Gallium Protoporphyrin in different concentrations in preventing adhesion formation after abdominal surgery. Materials and Methods: DS: 112 adult (8-10 week old) male Wistar albino rats were subjected to midline laparotomy and caecal abrasion, with 48 rats having an additional enterotomy and suturing. Kaolin (0.005g/ml) was applied to further accelerate adhesion formation. The abrasion model rats were randomized to receive saline, Chitogel, or Chitogel plus Deferiprone (5, 10 or 20 mM), together with Gallium Protoporphyrin (250μg/mL). The abrasion with enterotomy rats were randomised to receive saline, Chitogel or Chitogel with Deferiprone (1 or 5 mM). At day 21, rats were euthanised, and adhesions graded macroscopically and microscopically; the tensile strength of the repaired caecum was determined by an investigator blinded to the treatment groups. Results: Chitogel with Deferiprone 5 mM significantly reduced adhesion formation (p<0.01) when pathologically assessed in a rat abrasion model. Chitogel with Deferiprone 5 mM and 1 mM also significantly reduced adhesions (p<0.05) after abrasion with enterotomy. Def-Chitogel 1mM treatment did not weaken the enterotomy site with treated sites having significantly better tensile strength compared to control saline treated enterotomy rats. Conclusions: Chitogel with Deferiprone 1 mM constitutes an effective preventative anti-adhesion barrier after abdominal surgery in a rat model. Moreover, this therapeutic combination of agents is safe and does not weaken the healing of the sutured enterotomy site.Rajan Sundaresan Vediappan, Catherine Bennett, Clare Cooksley, John Finnie, Markus Trochsler, Ryan D. Quarrington, Claire F. Jones, Ahmed Bassiouni, Stephen Moratti, Alkis J. Psaltis, Guy Maddern, Sarah Vreugde, P.J. Wormal

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.Ryan D. Quarrington, Robert Bauze, Claire F. Jone

Quantitative evaluation of facet deflection, stiffness, strain and failure load during simulated cervical spine trauma

Abstract not availableRyan D. Quarrington, John J. Costi, Brian J.C. Freeman, Claire F. Jone

Elevated levels of active Transforming Growth Factor beta1 in the subchondral bone relate spatially to cartilage loss and impaired bone quality in human knee osteoarthritis

Abstract not availableD. Muratovic, D.M. Findlay, R.D. Quarrington, X. Cao, L.B. Solomon, G.J. Atkins, J.S. Kuliwab

Characterising spinal cerebrospinal fluid flow in the pig with phase-contrast magnetic resonance imaging

Background: Detecting changes in pulsatile cerebrospinal fuid (CSF) fow may assist clinical management decisions, but spinal CSF fow is relatively understudied. Traumatic spinal cord injuries (SCI) often cause spinal cord swelling and subarachnoid space (SAS) obstruction, potentially causing pulsatile CSF fow changes. Pigs are emerging as a favoured large animal SCI model; therefore, the aim of this study was to characterise CSF fow along the healthy pig spine. Methods: Phase-contrast magnetic resonance images (PC-MRI), retrospectively cardiac gated, were acquired for fourteen laterally recumbent, anaesthetised and ventilated, female domestic pigs (22–29 kg). Axial images were obtained at C2/C3, T8/T9, T11/T12 and L1/L2. Dorsal and ventral SAS regions of interest (ROI) were manually segmented. CSF fow and velocity were determined throughout a cardiac cycle. Linear mixed-efects models, with post-hoc comparisons, were used to identify diferences in peak systolic/diastolic fow, and maximum velocity (cranial/caudal), across spinal levels and dorsal/ventral SAS. Velocity wave speed from C2/C3 to L1/L2 was calculated. Results: PC-MRI data were obtained for 11/14 animals. Pulsatile CSF fow was observed at all spinal levels. Peak systolic fow was greater at C2/C3 (dorsal: − 0.32±0.14 mL/s, ventral: − 0.15±0.13 mL/s) than T8/T9 dorsally (− 0.04±0.03 mL/s; p0.05). Peak diastolic fow was greater at C2/C3 (0.29±0.08 mL/s) compared to T8/T9 (0.03±0.03 mL/s, p<0.001) dorsally, but not diferent ventrally (p=1.000). Cranial and caudal maximum velocity at C2/C3 were greater than thoracolumbar levels dorsally (p<0.001), and T8/T9 and L1/L2 ventrally (p=0.022). Diastolic velocity wave speed was 1.41±0.39 m/s dorsally and 1.22±0.21 m/s ventrally, and systolic velocity wave speed was 1.02±0.25 m/s dorsally and 0.91±0.22 m/s ventrally. Conclusions: In anaesthetised and ventilated domestic pigs, spinal CSF has lower pulsatile fow and slower velocity wave propagation, compared to humans. This study provides baseline CSF fow at spinal levels relevant for future SCI research in this animal model.Madeleine Amy Bessen, Christine Diana Gayen, Ryan David Quarrington, Angela Catherine Walls, Anna Victoria Leonard, Vartan Kurtcuoglu, and Claire Frances Jone

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 longterm 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, IL1β 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.Jessica M. Sharkey, Ryan D. Quarrington, Justin L. Krieg, Lola Kaukas, Renee J. Turner, Anna Leonard, Claire F. Jones, Frances Corriga