Degeneration of the intervertebral disc with new approaches for treating low back pain.

This review paper discusses the process of disc degeneration and the current understanding of cellular degradation in patients who present with low back pain. The role of surgical treatment for low back pain is analysed with emphasis on the proven value of spinal fusion. The interesting and novel developments of stem cell research in the treatment of low back pain are presented with special emphasis on the importance of the cartilaginous end plate and the role of IL-1 in future treatment modalities

Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models

Organ-on-chip (OOC) systems recapitulate key biological processes and responses in vitro exhibited by cells, tissues, and organs in vivo. Accordingly, these models of both health and disease hold great promise for improving fundamental research, drug development, personalized medicine, and testing of pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, the nature of which is tissue specific and may change with disease or injury. These biomechanical stimuli regulate cell behavior and can amplify, annul, or even reverse the response to a given biochemical cue or drug candidate. As such, the application of an appropriate physiological or pathological biomechanical environment is essential for the successful recapitulation of in vivo behavior in OOC models. Here we review the current range of commercially available OOC platforms which incorporate active biomechanical stimulation. We highlight recent findings demonstrating the importance of including mechanical stimuli in models used for drug development and outline emerging factors which regulate the cellular response to the biomechanical environment. We explore the incorporation of mechanical stimuli in different organ models and identify areas where further research and development is required. Challenges associated with the integration of mechanics alongside other OOC requirements including scaling to increase throughput and diagnostic imaging are discussed. In summary, compelling evidence demonstrates that the incorporation of biomechanical stimuli in these OOC or microphysiological systems is key to fully replicating in vivo physiology in health and disease

Hydroxyapatite nanoparticle injectable hydrogel scaffold to support osteogenic differentiation of human mesenchymal stem cells

Bone loss associated with degenerative disease and trauma is a clinical problem increasing with the aging population. Thus, effective bone augmentation strategies are required; however, many have the disadvantages that they require invasive surgery and often the addition of expensive growth factors to induce osteoblast differentiation. Here, we investigated a Laponite crosslinked, pNIPAMDMAc copolymer (L-pNIPAM-co-DMAc) hydrogel with hydroxyapatite nanoparticles (HAPna), which can be maintained as a liquid ex vivo, injected via narrowgauge needle into affected bone, followed by in situ gelation to deliver and induce osteogenic differentiation of human mesenchymal stem cells (hMSC). L-pNIPAMco-DMAc hydrogels were synthesised and HAPna added post polymerisation. Commercial hMSCs from one donor (Lonza) were incorporated in liquid hydrogel, the mixture solidified and cultured for up to 6 weeks. Viability of hMSCs was maintained within hydrogel constructs containing 0.5 mg/mL HAPna. SEM analysis demonstrated matrix deposition in cellular hydrogels which were absent in acellular controls. A significant increase in storage modulus (G’) was observed in cellular hydrogels with 0.5 mg/mL HAPna. Semi-quantitative immunohistochemistry and histological analysis demonstrated that bone differentiation markers and collagen deposition was induced within 48 h, with increased calcium deposition with time. The thermally triggered hydrogel system, described here, was sufficient without the need of additional growth factors or osteogenic media to induce osteogenic differentiation of commercial hMSCs. Preliminary data presented here will be expanded on multiple patient samples to ensure differentiation is seen in these samples. This system could potentially reduce treatment costs and simplify the tre

An in vitro investigation of the inflammatory response to the strain amplitudes which occur during high frequency oscillation ventilation and conventional mechanical ventilation

The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College Londo

Material Behaviours of Healthy, Degenerate and Hydrogel Injected Bovine Intervertebral Discs

Objectives Low back pain (LBP) is an increasing drain on developed economies due to direct medical costs and lost working days. The majority of medical costs can be attributed to long-term problems resulting from specific physiological conditions. Acute injury and/or chronic degeneration of the intervertebral disc (IVD) has been linked with long term pain with high levels of nerve in-growth in degenerate IVDs. The fact that disc degeneration is a structural failing and not just a pathogenesis of pain may lead to reduced mobility and quality of life (QOL). Mesenchymal stem cell (MSC) interventions have been proposed as a treatment for degenerate IVDs but little is known about how the injection of a hydrogel matrix required by such interventions affects the material properties of the intervertebral disc and what effects this might have on disc health. This study aims to determine the difference in material behaviours of healthy, degenerate and hydrogel injected IVDs subjected to cyclic loading simulating activities of daily living (ADL). Materials and Methods Bovine coccygeal discs were dissected whole from tail sections and split in to three equal test groups; healthy, degenerate and hydrogel injected. Degenerate and hydrogel injected groups were injected with a 2 mg/ml collagenase solution and incubated at 37°C for 2 hours to simulate moderate degeneration, the hydrogel injected group then received a hydrogel injection. All discs were then subjected to sinusoidal loading at 2Hz at force levels equivalent to those in the human spine during walking and mechanical data analysed to determine respective material behaviours of each group. Results Under axial loading simulating walking in the lumbar spine compression (absolute and relative strain) and stiffness of discs varied across all three test groups. Conclusions Cyclic loading simulating activities of daily living was found to result in different material behaviours in bovine intervertebral discs that were moderately degenerated and/or injected with hydrogel relative to healthy discs

Self-reflection and academic performance: is there a relationship?

The purposes of the present study were two-fold: first, to evaluate whether reflection journal writing was effective in promoting self-reflection and learning, and whether students become better at self-reflection if they engage continuously in reflection journal writing. To that end, the reflection journals of 690 first-year applied science students at a local polytechnic were studied by means of an automated coding procedures using software. Data was collected twice, once at the beginning and again towards the end of an academic year. Outcomes of the textual content analyses revealed that students reflected on both the process and contents of their learning: critical review of past learning experiences, learning strategies and summaries of what was learned. Correlational analyses showed weak to moderate inter-relationship

Collapse of a giant iceberg in a dynamic Southern Ocean marine ecosystem: In situ observations of A-68A at South Georgia

Large icebergs (>20 km long) are responsible for most of the freshwater discharged into the Southern Ocean. We report on in situ and satellite observations made during the break-up phase around South Georgia of the giant tabular iceberg A-68A. The in situ measurements were obtained during a 4-day visit by a research vessel in February 2021, where physical, chemical and biological measurements were made at a range of distances away from the main and subsidiary icebergs. These results were compared to a far-field station 133 km away. Up�stream of the iceberg field, water column structure was similar to ambient water although there was evidence of iceberg-associated phytoplankton as a likely remnant of the passage of the icebergs. Nevertheless, enhancement of primary productivity along the path of the icebergs was not resolved in either in situ or monthly mean satellite observations. There was a considerable brash-ice field moving ahead of the icebergs which limited the number of downstream sampling stations. One downstream station within 2 km of iceberg A-68P showed several ice-melt influenced features that distinguished it from most other stations. Firstly, there was a strong stratified meltwater influenced layer that reached to around 120 m. This had the effect of deepening underlying water masses, with the core of the temperature minimum layer around 50 m deeper than elsewhere. Secondly, there was evidence of rapid downward displacement of both particulate material and certain phytoplankton taxa that may be a further result of this water mass deepening. Thirdly, macronutrient profiles were altered, with concentrations of nitrate, silicic acid and phosphate characteristic of deeper layers being found closer to the surface and a dilution of the ambient nutrient pool just above the iceberg draft that we ascribe to meltwater released from basal melting. Meanwhile, nutrient recycling processes associated with organic matter remineralisation were also modified by the physical restructuring of the water column and biotic components. Finally, the ice-associated phytoplankton taxa Pseudo-nitszchia/Nitszchia, found in both upstream and downstream locations, were abundant at this < 2 km-distant station through melting out from the iceberg and subsequent rapid growth. Overall, we resolved alterations to water column structure, nutrient profiles and phytoplankton community composition at fine to medium scales around the iceberg field. Nevertheless, although there may have been longer term and larger scale impacts, the dynamic oceanographic environment, including the presence of a strong oceanographic front and shelf-edge processes, dominated during the collapse of A-68A