A finite element prediction of strain on cells in a highly porous collagen-glycosaminoglycan scaffold.

Tissue engineering often involves seeding cells into porous scaffolds and subjecting the scaffold to mechanical stimulation. Current experimental techniques have provided a plethora of data regarding cell responses within scaffolds, but the quantitative understanding of the load transfer process within a cell-seeded scaffold is still relatively unknown. The objective of this work was to develop a finite element representation of the transient and heterogeneous nature of a cell-seeded collagen-GAG-scaffold. By undertaking experimental investigation, characteristics such as scaffold architecture and shrinkage, cellular attachment patterns, and cellular dimensions were used to create a finite element model of a cell-seeded porous scaffold. The results demonstrate that a very wide range of microscopic strains act at the cellular level when a sample value of macroscopic (apparent) strain is applied to the collagen-GAG-scaffold. An external uniaxial strain of 10% generated a cellular strain as high as 49%, although the majority experienced less than approximately 5% strain. The finding that the strain on some cells could be higher than the macroscopic strain was unexpected and proves contrary to previous in vitro investigations. These findings indicate a complex system of biophysical stimuli created within the scaffolds and the difficulty of inducing the desired cellular responses from artificial environments. Future in vitro studies could also corroborate the results from this computational prediction to further explore mechanoregulatory mechanisms in tissue engineering.

Effects of intervertebral disk degeneration on the flexibility of the human thoracolumbar spine.

The objective of this study was to investigate the effects of intervertebral disk degeneration on the flexibility of the thoracolumbar spine in flexion and extension, both experimentally and computationally. A seven-level biomechanically tested human cadaveric spine (T11-L5) and a 3D finite element model of the same thoracolumbar spine were used for this purpose. The anatomically accurate computer model was generated from detailed computed tomography images and included the vertebral shell, the trabecular centrum, cartilage endplates, intervertebral disks, seven spinal ligament groups, and the facet joints. The cadaveric spinal segment and the specimen-specific finite element model were subjected to various compressive loads ranging from 75 to 975 N using the follower load principle and an oscillating bending moment of +/-5 Nm applied in the sagittal plane. The biomechanical behavior of the finite element model of the spine was validated with the experimental mechanical test data for the corresponding physical thoracolumbar spine specimen. In addition, the effect of intervertebral disk material property variation within the thoracolumbar spinal column on the spinal flexibility was extensively studied. The results of this study provided significant insight into how mechanical properties of the intervertebral disk influence spinal flexibility along the thoracolumbar spinal column. It was found that in order to get comparable results between experimental and computed data, the material properties of the intervertebral disks had to vary along the spinal column. However, these effects are diminished with increasing axial compressive load. Because of the trend between disk properties and spinal level, we further concluded that there might be a mechanism at play that links endplate size, body weight fraction, and segmental flexibility. More studies are needed to further investigate that relationship.

Generation of a finite element model of the thoracolumbar spine.

The goal of this study was to generate a realistic 3D FE model of the seven level thoracolumbar spine. This research focused on the development of a robust and efficient procedure for generating anatomical 3D FE models, directly from a series of medical images, i.e., CT data. A complex model of the spine was created by combining two different modelling approaches, namely the CAD and STL-CAD methods. In addition, the entire meshing procedure for the vertebrae was significantly speeded up by combining 3D tetrahedral elements with brick elements, relative to conventional mapped mesh generation procedures. The resulting model generation method allowed for flexibility in element choice and in element type combinations. The model was subjected to various compressive loads to asses the overall behaviour of the spine. This case study was performed to illustrate the usefulness of the FE model. In the authors' opinion, the model presented is an important tool in computational spine research as it can provide general information on spinal behaviour under various loading conditions whether healthy, diseased or damaged.

Vertebral osteoporosis and trabecular bone quality.

Vertebral fractures due to osteoporosis commonly occur under non-traumatic loading conditions. This problem affects more than 1 in 3 women and 1 in 10 men over a lifetime. Measurement of bone mineral density (BMD) has traditionally been used as a method for diagnosis of vertebral osteoporosis. However, this method does not fully account for the influence of changes in the trabecular bone quality, such as micro-architecture, tissue properties and levels of microdamage, on the strength of the vertebra. Studies have shown that deterioration of the vertebral trabecular architecture results in a more anisotropic structure which has a greater susceptibility to fracture. Transverse trabeculae are preferentially thinned and perforated while the remaining vertical trabeculae maintain their thickness. Such a structure is likely to be more susceptible to buckling under normal compression loads and has a decreased ability to withstand unusual or off-axis loads. Changes in tissue material mechanical properties and levels of microdamage due to osteoporosis may also compromise the fracture resistance of vertebral trabecular bone. New diagnostic techniques are required which will account for the influence of these changes in bone quality. This paper reviews the influence of the trabecular architecture, tissue properties and microdamage on fracture risk for vertebral osteoporosis. The morphological characteristics of normal and osteoporotic architectures are compared and their potential influence on the strength of the vertebra is examined. The limitations of current diagnostic methods for osteoporosis are identified and areas for future research are outlined.

Activity of Staphylococcus epidermidis phenol-soluble modulin peptides expressed in Staphylococcus carnosus.

Staphylococcus epidermidis releases a group of peptides termed phenol-soluble modulin (PSM) that stimulate macrophages. The structure of 3 peptides (PSM alpha, PSM beta, and PSM gamma ) have been described. We report a fourth peptide (PSM delta ), which is a 23mer with the structure fMSIVSTIIEVVKTIVDIVKKFKK. The gene for each of the 4 peptides was introduced singly into Staphylococcus carnosus, and the PSM-like activity of culture medium and bacterial extract were significantly greater than those of the parent strain. PSM peptides from each of the S. carnosus-expressing strains were purified and analyzed by liquid chromatography-mass spectrometry. The products, which appeared to form aggregates, were active in the activation of human immunodeficiency virus type 1 long-terminal repeat and the production of tumor necrosis factor- alpha by the macrophage cell line THP-1. These findings suggest that PSM peptides are responsible, in part, for the modulin-like activity of staphylococci and may contribute to the development of severe staphylococcal sepsis.

Differential diagnosis of dementia: a prospective evaluation of the DAT Inventory.

OBJECTIVE: To compare prospectively the concordance between the diagnosis of dementia based on clinical criteria and using the DAT Inventory. DESIGN, SETTING, AND PARTICIPANTS: A prospective study of 81 consecutive patients referred to a Memory Clinic. Only patients for whom a definitive diagnosis of dementia was established after 8 to 20 months follow-up were retained in the study (n = 76). MEASUREMENTS: The sensitivity, specificity, positive and negative predictive values, and overall diagnostic accuracy of the DAT Inventory were calculated. Kappa values were also computed. RESULTS: Based on all patients (n = 76), sensitivity and specificity were 71% and 95%, respectively, with 98% positive prediction, 56% negative prediction, 78% overall accuracy, and kappa of 0.54. Of 21 cases not meeting NINCDS/ADRDA criteria for DAT, one patient with multi-infarct dementia was misclassified as DAT on the DAT Inventory. Of 55 DAT cases (NINCDS/ADRDA criteria), 16 patients, predominantly very mild or mixed cases, were classified as non-DAT on the DAT Inventory. When mixed, very mild, and borderline cases were excluded (remaining n = 54), DAT Inventory sensitivity increased to 94%, and specificity remained unchanged at 95%, with 97% positive and 91% negative prediction, 94% overall accuracy, and kappa of 0.88. CONCLUSIONS: In general, scores above the designated cutoff point (> 14/20) on the DAT Inventory are consistent with a clinical diagnosis of DAT (NINCDS/ADRDA criteria). Concordance is best in cases of mild to moderate dementia (Clinical Dementia Rating 1-2). The Inventory is less discriminating as a differential diagnostic instrument in cases of very mild dementia, atypical presentations of DAT, or in cases of mixed pathology.