Development of a standardized histopathology scoring system for intervertebral disc degeneration in rat models: An initiative of the ORS spine section

Background Rats are a widely accepted preclinical model for evaluating intervertebral disc (IVD) degeneration and regeneration. IVD morphology is commonly assessed using histology, which forms the foundation for quantifying the state of IVD degeneration. IVD degeneration severity is evaluated using different grading systems that focus on distinct degenerative features. A standard grading system would facilitate more accurate comparison across laboratories and more robust comparisons of different models and interventions. Aims This study aimed to develop a histology grading system to quantify IVD degeneration for different rat models. Materials & Methods This study involved a literature review, a survey of experts in the field, and a validation study using 25 slides that were scored by 15 graders from different international institutes to determine inter- and intra-rater reliability. Results A new IVD degeneration grading system was established and it consists of eight significant degenerative features, including nucleus pulposus (NP) shape, NP area, NP cell number, NP cell morphology, annulus fibrosus (AF) lamellar organization, AF tears/fissures/disruptions, NP-AF border appearance, as well as endplate disruptions/microfractures and osteophyte/ossification. The validation study indicated this system was easily adopted, and able to discern different severities of degenerative changes from different rat IVD degeneration models with high reproducibility for both experienced and inexperienced graders. In addition, a widely-accepted protocol for histological preparation of rat IVD samples based on the survey findings include paraffin embedding, sagittal orientation, section thickness < 10 μm, and staining using H&E and/or SO/FG to facilitate comparison across laboratories. Conclusion The proposed histological preparation protocol and grading system provide a platform for more precise comparisons and more robust evaluation of rat IVD degeneration models and interventions across laboratories

Magneto-Driven Gradients of Diamagnetic Objects for Engineering Complex Tissues

Engineering complex tissues represents an extraordinary challenge and, to date, there have been few strategies developed that can easily recapitulate native‐like cell and biofactor gradients in 3D materials. This is true despite the fact that mimicry of these gradients may be essential for the functionality of engineered graft tissues. Here, a non‐traditional magnetics‐based approach is developed to predictably position naturally diamagnetic objects in 3D hydrogels. Rather than magnetizing the objects within the hydrogel, the magnetic susceptibility of the surrounding hydrogel precursor solution is enhanced. In this way, a range of diamagnetic objects (e.g., polystyrene beads, drug delivery microcapsules, and living cells) are patterned in response to a brief exposure to a magnetic field. Upon photo‐crosslinking the hydrogel precursor, object positioning is maintained, and the magnetic contrast agent diffuses out of the hydrogel, supporting long‐term construct viability. This approach is applied to engineer cartilage constructs with a depth‐dependent cellularity mirroring that of native tissue. These are thought to be the first results showing that magnetically unaltered cells can be magneto‐patterned in hydrogels and cultured to generate heterogeneous tissues. This work provides a foundation for the formation of opposing magnetic‐susceptibility‐based gradients within a single continuous material

Intervertebral disc degeneration and regeneration: a motion segment perspective

Back and neck pain have become primary reasons for disability and healthcare spending globally. While the causes of back pain are multifactorial, intervertebral disc degeneration is frequently cited as a primary source of pain. The annulus fibrosus (AF) and nucleus pulposus (NP) subcomponents of the disc are common targets for regenerative therapeutics. However, disc degeneration is also associated with degenerative changes to adjacent spinal tissues, and successful regenerative therapies will likely need to consider and address the pathology of adjacent spinal structures beyond solely the disc subcomponents. This review summarises the current state of knowledge in the field regarding associations between back pain, disc degeneration, and degeneration of the cartilaginous and bony endplates, the AF-vertebral body interface, the facet joints and spinal muscles, in addition to a discussion of regenerative strategies for treating pain and degeneration from a whole motion segment perspective

Mixing in Circular and Non-circular Jets in Crossflow

Coherent structures and mixing in the flow field of a jet in crossflow have been studied using computational (large eddy simulation) and experimental (particle image velocimetry and laser-induced fluorescence) techniques. The mean scalar fields and turbulence statistics as determined by both are compared for circular, elliptic, and square nozzles. For the latter configurations, effects of orientation are considered. The computations reveal that the distribution of a passive scalar in a cross-sectional plane can be single- or double-peaked, depending on the nozzle shape and orientation. A proper orthogonal decomposition of the transverse velocity indicates that coherent structures may be responsible for this phenomenon. Nozzles which have a single-peaked distribution have stronger modes in transverse direction. The global mixing performance is superior for these nozzle types. This is the case for the blunt square nozzle and for the elliptic nozzle with high aspect ratio. It is further demonstrated that the flow field contains large regions in which a passive scalar is transported up the mean gradient (counter-gradient transport) which implies failure of the gradient diffusion hypothesis

A perspective on the ORS Spine Section initiative to develop a multi‐species JOR Spine histopathology series

This perspective summarizes the genesis, development, and potential future directions of the multispecies JOR Spine histopathology series

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: recommendations of the ORS spine section

Intervertebral disc degeneration is strongly associated with chronic low back pain, a leading cause of disability worldwide. Current back pain treatment approaches (both surgical and conservative) are limited to addressing symptoms, not necessarily the root cause. Not surprisingly therefore, long‐term efficacy of most approaches is poor. Cell‐based disc regeneration strategies have shown promise in preclinical studies, and represent a relatively low‐risk, low‐cost, and durable therapeutic approach suitable for a potentially large patient population, thus making them attractive from both clinical and commercial standpoints. Despite such promise, no such therapies have been broadly adopted clinically. In this perspective we highlight primary obstacles and provide recommendations to help accelerate successful clinical translation of cell‐based disc regeneration therapies. The key areas addressed include: (a) Optimizing cell sources and delivery techniques; (b) Minimizing potential risks to patients; (c) Selecting physiologically and clinically relevant efficacy metrics; (d) Maximizing commercial potential; and (e) Recognizing the importance of multidisciplinary collaborations and engaging with clinicians from inception through to clinical trials

Large Eddy Simulation of Turbulent Flows in Combustor Related Geometries

Numerical simulations using Large Eddy Simulation (LES) are applied to turbulent swirling flow fields. The swirling motion is often introduced into combustors to act as flame holders or enhance the mixing between species. Different turbulence models capture the swirling motion more or less accurately. LES is well suited for understanding details of swirling flows. It resolves all the large scales in the flow field and only the small scales have to be modeled. The small unresolved scales are the Subgrid Scales (SGS) and the model must take into account the interaction between the small scales and their influence on the resolved scales. In order to separate the effects from the SGS models and the numerical scheme, the problem must be well resolved and be of high order. SGS models have been applied, investigated and compared in swirling flow fields. Four SGS models are considered: an implicit, a stress similarity, a dynamic divergence and an exact differential model. The implicit model uses no SGS model. For the stress similarity model, similar behaviour between the resolved and unresolved stresses is assumed. The model parameter in the dynamic divergence model are depending upon both space and time and it is recalculated during the whole simulation. If a particular form of differential filter function is applied, an explicit expression of the SGS stress tensor can be received. This is the exact differential model. In the simulations, the stress similarity model is shown to have the largest effect on the results. Otherwise, the SGS models only show minor effects on both mean velocities and turbulence intensities. A high order Cartesian grid method have been proposed and employed in the simulations. Cartesian grids have features that are very suitable for LES. The grid generation is simple and fast, it does not require a lot of computational storage and the discretized governing equations can be easily extended to higher orders. The drawback of Cartesian grids is that it does not represent complex geometries correctly. The boundary conditions can be misplaced by as much as a cell size and this reduces the order of the solution. A high order wall treatment is proposed to handle the low order wall problem and it is incorporated into the Cartesian grid method. The high order Cartesian grid method is shown to maintain the order of the discretization

Matematikundervisning genom problemlösning : En studie om lärares möjligheter att förändra sin undervisning

Syftet med denna studie var att undersöka och visa flera sätt att undervisa i matematik genom problemlösning samt att undersöka vilken inverkan forskning inom området har i praktiken. I undersökningen ingick intervjuer och lektionsobservationer hos tre lärare som systematiskt använder sig av problemlösning i sin undervisning. Resultaten från undersökningen visar att problemlösning kan användas på olika sätt och med olika syfte i matematikundervisningen. De visar också att det finns både gemensamma och särskiljande aspekter mellan de observerade lektionerna samt mellan lärarnas synsätt på problemlösning. Dessutom tyder resultaten på en viss sammankoppling mellan lärarnas undervisning och de forskningsresultat som finns rapporterade i litteraturen. Samtidigt indikerar resultaten att varje lärare har utvecklat en personlig undervisningsform utifrån sina egna förutsättningar som i några aspekter inte överensstämmer med de rapporterade resultaten inom området.The purpose of this study was to explore and give examples of teaching mathematics through problem solving and to investigate the impact of research in the field of teachers' practice. The investigation included interviews and lesson observations with three teachers which systematically use problem solving in their teaching. The results of my investigation showed that problem solving can be used in different ways and with different purposes in the mathematics education. They also showed that there are both common and distinctive aspects in the observed practices of teaching and in the teachers' approach to problem solving. In addition, the results suggest some connection between the teachers' teaching and the research findings reported in the literature. However, the results also indicate that each teacher has developed a personalized form of teaching according to their individual circumstances and that their practice may in some aspects differ from those results reported about teaching through problem solving