Objectives. Understanding lumbar facet joint involvement and biomechanical changes post spinal fusion is limited. This study aimed to establish an in vitro model assessing mechanical effects of fusion on human lumbar facet joints, employing synchronized motion, pressure, and stiffness analysis. Methods and Results. Seven human lumbar spinal units (age 54 to 92, ethics 15/YH/0096) underwent fusion via a partial nucleotomy model mimicking a lateral cage approach with PMMA cement injection. Mechanical testing pre and post-fusion included measuring compressive displacement and load, local motion capture, and pressure mapping at the facet joints. pQCT imaging (82 microns isotropic) was carried out at each stage to assess the integrity of the vertebral endplates and quantify the amount of cement injected. Before fusion, relative facet joint displacement (6.5 ± 4.1 mm) at maximum load (1.1 kN) exceeded crosshead displacement (3.9 ± 1.5 mm), with loads transferred across both facet joints. After fusion, facet displacement (2.0 ± 1.2 mm) reduced compared to pre-fusion, as was the crosshead displacement (2.2 ± 0.6 mm). Post-fusion loads (71.4 ± 73.2 N) transferred were reduced compared to pre-fusion levels (194.5 ± 125.4 N). Analysis of CT images showed no endplate damage post-fusion, whilst the IVD tissue: cement volume ratio did not correlate with the post-fusion behaviour of the specimens. Conclusion. An in vitro model showed significant facet movement reduction with stand-alone interbody cage placement. This technique identifies changes in facet movement post-fusion, potentially contributing to subsequent spinal degeneration, highlighting its utility in biomechanical assessment. Conflicts of interest. None. Sources of funding. This work was funded by EPSRC, under grant EP/W015617/1

The lordosis distribution index (LDI) describes distribution of lumbar lordosis, measured as the % of lower lumbar lordosis (L4-S1) compared to global lordosis (L1-S1) with normal value 50–50%. Maldistributed LDI is associated with higher revision in short lumbar fusions, 4 vertebrae1. We hypothesise maldistributed LDI is also associated with mechanical failure in longer fusions. Retrospective review of 29 consecutive ASD patients, aged 55+, undergoing long lumbar fusion, 4 levels, with >3-years follow-up. LDI, pelvic incidence (PI) and sagittal vertical axis (SVA) were measured on pre- and post-op whole spine standing X-rays (Fig A and B). Patients were categorized according to their pelvic incidence (PI) and postoperative LDI: Normal (LDI 50 80), Hypolordotic (LDI < 50), or Hyperlordotic (LDI > 80) and assessed for failure rate compared to normal LDI and PI <60. Mean follow-up 4.5 years. 19 patients had mechanical failures including junctional failure and metalware fracture. PI >60o was associated with higher mechanical failure rates (Chi^2 p<0.05). Hypolordotic LDI was associated with 82% mechanical failure (Chi^2 p<0.001), Hyperlordotic 88% mechanical failure (Chi^2 p<0.001) and Normal 8% mechanical failure (Table 1). Maldistributed LDI, whether Hyperlordotic or Hypolordotic, correlated with 10× greater mechanical failure rate compared to Normal LDI in long fusions. LDI is a useful measurement that should be considered, especially in high PI patients

We previously reported that osteoblasts at the curve apex in adolescent idiopathic scoliosis (AIS) exhibit a differential phenotype, compared to non-curve osteoblasts(1). However, the Hueter-Volkmann principle on vertebral body growth in spinal deformities (2) suggests this could be secondary to altered biomechanics. This study examined whether non-curve osteoblasts subjected to mechanical strain resemble the transcriptomic phenotype of curve apex osteoblasts. Facet spinal tissue was collected perioperatively from three sites, (i) the concave and (ii) convex side at the curve apex and (iii) from outside the curve (non-curve) from six AIS female patients (age 13–18 years; NRES 19/WM/0083). Non-curve osteoblasts were subjected to strain using a 4-point bending device. Osteoblast phenotype was determined by RNA sequencing and bioinformatic pathway analysis. RNAseq revealed that curve apex osteoblasts exhibited a differential transcriptome, with 1014 and 1301 differentially expressed genes (DEGs; p<0.05, fold-change >1.5) between convex/non-curve and concave/non-curve sites respectively. Non-curve osteoblasts subjected to strain showed increased protein expression of the mechanoresponsive biomarkers COX2 and C-Fos. Comparing unstimulated vs strain-induced non-curve osteoblasts, 423 DEGs were identified (p<0.05, fold-change >1.5). Of these DEGs, only 5% and 6% were common to the DEGs found at either side of the curve apex, compared to non-curve cells. Bioinformatic analysis of these strain-induced DEGs revealed a different array of canonical signalling pathways and cellular processes, to those significantly affected in cells at the curve apex. Mechanical strain of AIS osteoblasts in vitro did not induce the differential transcriptomic phenotype of AIS osteoblasts at the curve apex

Purposes of the study and background. An increasing number of clinical studies involving a range of chronic pain conditions report widespread mechanical pressure pain hypersensitivity, which is commonly interpreted as resulting from central sensitization (CS). Secondary hyperalgesia (increased pinprick sensitivity surrounding the site of injury) is considered to be a manifestation of central sensitization. However, it has not been rigorously tested whether central sensitization induced by peripheral nociceptive input, involves widespread mechanical pressure pain hypersensitivity. The aim of this study was to assess whether high frequency electrical stimulation (HFS), which induces a robust secondary hyperalgesia, also induces a widespread decrease of pain pressure thresholds (PPTs). Summary of the methods and results. We measured PPTs bilaterally on the temples (temporalis muscles), on the legs (tibialis anterior muscles) and on the ventral forearm (flexor carpi radialis muscles) before, 20 min after, and 45 min after applying HFS on the ventral forearm of sixteen healthy young volunteers. To evaluate the presence of secondary hyperalgesia, mechanical pin-prick sensitivity was assessed on the skin surrounding the site where HFS was applied and also on the contralateral arm. HFS induced a significant increase in mechanical pinprick sensitivity on the HFS-treated arm. However, HFS did not decrease PPTs either in the area of increased pinprick sensitivity nor at more distant sites. Conclusion. The present study provides no evidence for the hypothesis that central sensitization, induced after intense activation of skin nociceptors, involves a widespread decrease of PPTs. No conflicts of interest. Sources of Funding: This study was funded by the Université Catholique de Louvain

To investigate whether restoration of mechanical function and spinal load-sharing following vertebroplasty depends upon cement distribution. Fifteen pairs of cadaver motion segments (51-91 yr) were loaded to induce fracture. One from each pair underwent vertebroplasty with PMMA, the other with a resin (Cortoss). Various mechanical parameters were measured before and after vertebroplasty. Micro-CT was used to determine volumetric cement fill, and plane radiographs (sagittal, frontal, and axial) to determine areal fill, for the whole vertebral body and for several specific regions. Correlations between volumetric fill and areal fill for the whole vertebral body, and between regional volumetric fill and changes in mechanical parameters following vertebroplasty, were assessed using linear regression. For Cortoss, areal and volumetric fills were significantly correlated (R=0.58-0.84) but cement distribution had no significant effect on any mechanical parameters following vertebroplasty. For PMMA, areal fills showed no correlation with volumetric fill, suggesting a non-uniform distribution of cement that influenced mechanical outcome. Increased filling of the vertebral body adjacent to the disc was associated with increased intradiscal pressure (R=0.56, p<0.05) in flexed posture, and reduced neural arch load bearing (F. N. ) in extended posture (R=0.76, p<0.01). Increased filling of the anterior vertebral body was associated with increased bending stiffness (R=0.55, p<0.05). Cortoss tends to spread evenly within the vertebral body, and its distribution has little influence on the mechanical outcome of vertebroplasty. PMMA spreads less evenly, and its mechanical benefits are increased when cement is concentrated in the anterior vertebral body and adjacent to the intervertebral disc

Purpose of the study and background. The preliminary study aimed to establish clinical and research expert opinion with regards to the key components of an assessment of a person with Mechanical Low Back Pain (MLBP). We aimed to identify the key subjective questions and objective tests which would be helpful for clinicians to develop the most appropriate self-management exercise programme. This is the first part of the study to develop the ‘Back-to-Fit’ digital tool offering personalised self-management exercise solutions for people with MLBP. Summary of the methods. A Bristol online survey which included a questionnaire with a series of open and closed questions was developed using the literature and was distributed among clinicians/researchers with a background in the clinical management of MLBP. The questionnaire included 6 demographic questions followed by sections related to subjective questions and objective tests of the MLBP assessment. 71 participants responded to the survey. Results. In the subjective assessment component, ≥80% level of agreement was obtained for 17 of 26 proposed subjective questions and 05 of the 21 suggested objective tests. Two more questions and two objective tests to be included in the assessment had been suggested by the partcipants. Conclusion. These expert agreements on questions and opinions provides an indication of the key subjective and objective components to be included in a self-assessment tool in a personalised self-management platform for MLBP. Further testing with a multiple round Delphi study in a large sample of experts is now required to obtain consensus for the above findings. Conflicts of interest: No conflicts of interest. Sources of funding: Biomechanics and Bioengineering Research Centre Versus Arthritis, Cardiff University, UK

This short contribution aims to explain how intervertebral disc ‘degeneration’ differs from normal ageing, and to suggest how mechanical loading and constitutional factors interact to cause disc degeneration and prolapse. We suggest that disagreement on these matters in medico-legal practice often arises from a misunderstanding of the nature of ‘soft-tissue injuries’

Background. Several theories have been put forward with respect to the mechanical role of the thoracolumbar fascia (TLF) but none have been substantiated in part due to an inability to explore its function in vivo. This study explored the use of ultrasound to image the layers of the TLF in vivo. Methods. Initially a cadaveric dissection of the fascia was performed to gain an appreciation of the 3-D orientation and representation of the TLF in the lumbar region. A conventional ultrasound system (Diasus, Dynamic Imaging Ltd) was then used to image the 3 layers of the fascia on 40 normal subjects (18 males and 22 females, mean age 27.3±5.8 years) and the reliability of these measures was investigated on a subset of this population. Results. Using ultrasound, the posterior and middle layer of the TLF could be readily identified, however it was not possible to visualise the anterior layer due to the limitations of the scanner used. The thickness of the posterior layer ranged from 1.3 ±0.4 to 1.5±0.4 mm depending on location relative to the spinous process. The middle layer tended to be thinner being 1.0±0.4mm on average. Intra-observer errors were within acceptable ranges, although not ideal. Conclusion. Ultrasound may be an important tool for understanding the mechanical role of fascia, however this would necessitate the use of high resolution scanner to enhance the reliability of images. Further work is required to image changes in the presentation of fascia in different loaded functional positions

Introduction

Decreasing endplate porosity has been proposed as a risk factor for intervertebral disc degeneration, because it interferes with disc metabolite transport. However, endplate porosity has recently been shown to increase with age and disc degeneration. We hypothesise that this increase reflects adaptive remodelling in response to altered loading from adjacent discs.

Background

Low back pain (LBP) is widespread in all populations and is a worldwide health problem, which poses substantial challenges for clinical management. Individuals with LBP may reduce their symptoms by implementing self-managed at-home interventions. The theoretical design of the LumbaCurve™ promotes the principles of a passive gravity-assisted traction (PGAT) stretch of the lumbar and sacral region in order to reduce LBP. This study aimed to assess the clinical effectiveness of the LumbaCurve™ in the management of LBP when compared to a control group of standardised care.

Aims. Postoperative complication rates remain relatively high after adult spinal deformity (ASD) surgery. The extent to which modifiable patient-related factors influence complication rates in patients with ASD has not been effectively evaluated. The aim of this retrospective cohort study was to evaluate the association between modifiable patient-related factors and complications after corrective surgery for ASD. Methods. ASD patients with two-year data were included. Complications were categorized as follows: any complication, major, medical, surgical, major mechanical, major radiological, and reoperation. Modifiable risk factors included smoking, obesity, osteoporosis, alcohol use, depression, psychiatric diagnosis, and hypertension. Patients were stratified by the degree of baseline deformity (low degree of deformity (LowDef)/high degree of deformity (HighDef): below or above 20°) and age (Older/Younger: above or below 65 years). Complication rates were compared for modifiable risk factors in each age/deformity group, using multivariable logistic regression analysis to adjust for confounders. Results. A total of 480 ASD patients met the inclusion criteria. By two years, complication rates were 72% ≥ one complication, 28% major, 21% medical, 27% surgical, 11% major radiological, 8% major mechanical, and 22% required reoperation. Younger LowDef patients with osteoporosis were more likely to suffer either a major mechanical (odds ratio (OR) 5.9 (95% confidence interval (CI) 1.1 to 36.9); p = 0.048) or radiological complication (OR 7.0 (95% CI 1.9 to 25.9); p = 0.003). Younger HighDef patients were much more likely to develop complications if obese, especially major mechanical complications (OR 2.8 (95% CI 1.1 to 8.6); p = 0.044). Older HighDef patients developed more complications when diagnosed with depression, including major radiological complications (OR 3.5 (95% CI 1.1 to 10.6); p = 0.033). Overall, a diagnosis of depression proved to be a risk factor for the development of major radiological complications (OR 2.4 (95% CI 1.3 to 4.5); p = 0.005). Conclusion. Certain modifiable patient-related factors, especially osteoporosis, obesity, and mental health status, are associated with an increased risk of complications after surgery for spinal deformity. Surgeons should look for these conditions when assessing a patient for surgery, and optimize them to the fullest extent possible before proceeding to surgical correction so as to minimize the prospect of postoperative morbidity. Cite this article: Bone Joint J 2022;104-B(11):1249–1255

Aims. The aim of this study was to investigate the impact of the level of upper instrumented vertebra (UIV) in frail patients undergoing surgery for adult spine deformity (ASD). Methods. Patients with adult spinal deformity who had undergone T9-to-pelvis fusion were stratified using the ASD-Modified Frailty Index into not frail, frail, and severely frail categories. ASD was defined as at least one of: scoliosis ≥ 20°, sagittal vertical axis (SVA) ≥ 5 cm, or pelvic tilt ≥ 25°. Means comparisons tests were used to assess differences between both groups. Logistic regression analyses were used to analyze associations between frailty categories, UIV, and outcomes. Results. A total of 477 patients were included (mean age 60.3 years (SD 14.9), mean BMI 27.5 kg/m. 2. (SD 5.8), mean Charlson Comorbidity Index (CCI) 1.67 (SD 1.66)). Overall, 74% of patients were female (n = 353), and 49.6% of patients were not frail (237), 35.4% frail (n = 169), and 15% severely frail (n = 71). At baseline, differences in age, BMI, CCI, and deformity were significant (all p = 0.001). Overall, 15.5% of patients (n = 74) had experienced mechanical complications by two years (8.1% not frail (n = 36), 15.1% frail (n = 26), and 16.3% severely frail (n = 12); p = 0.013). Reoperations also differed between groups (20.2% (n = 48) vs 23.3% (n = 39) vs 32.6% (n = 23); p = 0.011). Controlling for osteoporosis, baseline deformity, and degree of correction (by sagittal age-adjusted score (SAAS) matching), frail and severely frail patients were more likely to experience mechanical complications if they had heart failure (odds ratio (OR) 6.6 (95% CI 1.6 to 26.7); p = 0.008), depression (OR 5.1 (95% CI 1.1 to 25.7); p = 0.048), or cancer (OR 1.5 (95% CI 1.1 to 1.4); p = 0.004). Frail and severely frail patients experienced higher rates of mechanical complication than ‘not frail’ patients at two years (19% (n = 45) vs 11.9% (n = 29); p = 0.003). When controlling for baseline deformity and degree of correction in severely frail and frail patients, severely frail patients were less likely to experience clinically relevant proximal junctional kyphosis or failure or mechanical complications by two years, if they had a more proximal UIV. Conclusion. Frail patients are at risk of a poor outcome after surgery for adult spinal deformity due to their comorbidities. Although a definitively prescriptive upper instrumented vertebra remains elusive, these patients appear to be at greater risk for a poor outcome if the upper instrumented vertebra is sited more distally. Cite this article: Bone Joint J 2024;106-B(11):1342–1347

Purpose of study and background. Psychological factors are considered to play a role in development and maintenance of chronic low back pain (CLBP). Stress or anxiety can change pain sensitivity; however, this has predominantly been studied in healthy individuals with limited work in individuals with musculoskeletal pain. The objective of this study was to quantify the effect of acute exposure to a psychosocial stressor on mechanical pain sensitivity in individuals with and without CLBP. Summary of methods and results. Six individuals with CLBP and 10 individuals without CLBP performed a 10-minute computer task under conditions of low and high psychosocial stress. Psychosocial stress was manipulated using mental maths and memory tasks combined with social evaluative threat. The effect of the stressor was evaluated using blood pressure, heart rate and the state anxiety component of the Spielberger State-Trait Anxiety Index. Mechanical pressure pain threshold (PPT) was recorded on the tibialis anterior muscle using a handheld digital pressure algometer. The stress manipulation increased self-reported anxiety (p<0.001), but not blood pressure or heart rate (p>0.06). Change in PPT from low to high stress was greater in the CLBP group (median ΔPPT = −0.5 kg/cm. 2. ) than in the control group (−0.15 kg/cm. 2. ; p=0.005). Conclusion. Individuals experienced an increase in pain sensitivity after acute exposure to a stressor designed to mimic low-level workplace stressors, and this increase was greater in individuals with CLBP than asymptomatic individuals. These results indicate that this experimental model can be used to study links between pain sensitivity and psychosocial stressors and increase our understanding of their potential role in CLBP. Conflicts of Interest: No conflicts of interest. Sources of funding: No funding obtained

Background. We have previously reported an injectable hydrogel (NPgel), which could deliver patients own stem cells, via small bore needles, decreasing damage to the annulus fibrosus. NPgel drives differentiation to NP cells and can inhibit the degenerate niche. However, clinical success of NPgel is dependent on the capacity to inject NPgel into naturally degenerate human discs, restore mechanical function to the IVD, prevent extrusion during loading and induce regeneration. This study assessed injectability of NPgel into human IVD, influence on mechanical properties, regeneration ability in an ex vivo culture system and retention under failure testing. Methodology. Cadaveric human discs were used to calculate disc height and to determine Youngs Modulus during simulated walking pre and post injection of NPgel, extrusion testing performed. Whole human IVDs were injected with NPgel +/− human BMPCs and maintained in culture under physiological loading regime for 4 weeks. Pre and post culture MRI imaging and in line biomechanical characteristics determined. Histology and immunochemistry performed for anabolic and catabolic factors. Results. NPgel injection significantly increased disc height and Youngs modulus with no extrusion observed during failure testing. T1ρ intensity was increased during culture in those injected with NPgel +/− cells compared to non-injected discs, and biomechanical restoration. Histological analysis has demonstrated excellent tissue attachment to the injected gel, and cellular migration into acellular gel systems. With increased matrix production and decreased catabolic factor expression. Conclusion. These results provide essential proof of concept data supporting the use of NPgel as an injectable therapy for disc regeneration. Conflict of interest: C Le Maitre & C Sammon are inventors on the hydrogel discussed. Funding: This work was funded by MRC and Versus Arthritis

Background. An improved understanding of intervertebral disc (IVD) structure and function is required for treatment development. Loading induces micro-fractures at the interface between the nucleus pulposus (NP) and the annulus fibrosus (AF), which is hypothesized to induce a cascade of cellular changes leading to degeneration. However, there is limited understanding of the structural relationship between the NP and AF at this interface and particularly response to load. Here, X-ray scattering is utilised to provide hierarchical morphometric information of collagen structure across the IVD, especially the interface region under load. Methodology. IVDs were imaged using the I22 SAXS/WAXS beamline at Diamond Light Source. Peaks associated with the D-banded structure of collagen fibrils were fitted to quantify their azimuthal distribution, as well the magnitude and direction of internal strains under static and applied strain (0–20%). Results. IVD tissue regions exhibited structural “AF-like” and “NP-like” fingerprints. Demonstrating high internal strains on collagen fibres particularly within the NP region of the disc. AF and NP regions showed distinct collagen orientation and internal strains with an apparent lack of bracing structure seen at the interface between the differential mechanical tissues. X-ray scattering under tensile strain provided structural information at high resolution, with clear differences observed between normal and degenerate discs under load. Conclusion. X ray scattering has been utilised to develop an improved understanding of collagen structure across the intervertebral disc which can be utilised to gain an increased understanding of load induced propagation of micro fissures and disc degeneration. Conflict of Interest: No conflict of interest. Funding: BioPro Network, UCL for funding this study through support from the MRC (MR/R025673/1)

Introduction. Nucleus replacement surgery has the potential to be an early treatment option for chronic lower back pain. The surgery involves removal (nuclectomy) and replacement of the native degenerated nucleus with a material designed to restore the disc's physiological properties. Multiple techniques have been considered to perform a nuclectomy, however the advantages and disadvantages of each are not well understood. The aim of this study was to quantitatively compare three nuclectomy techniques: automated-shaver, rongeurs, and laser. Methods and results. Fifteen human vertebra-disc-vertebra lumbar specimens were split into three groups. Before and after nuclectomy axial mechanical tests were performed and T2-weighted 9.4T MRIs were acquired for each specimen. Using the automated-shaver and rongeur similar volumes of disc material were removed (2.51±1.10% and 2.76±1.39% of the total disc volume, respectively), whilst considerably less material was removed when using the laser (0.12±0.07%). Using the automated-shaver and rongeur significantly reduced the toe-region stiffness, while the linear region stiffness was significantly reduced only in the rongeur group. From the MRIs, more homogeneous cavities were seen in the center of the disc when using the automated shaver compared to rongeur, whilst laser ablation resulted in small, localized cavities. Conclusion. Results suggest that the current laser parameters are not suitable for removal of large volumes of material unless the technique is optimised for this application. Both rongeurs and automated-shavers can be used to remove large volumes of material but the reduced risk of collateral damage to surrounding tissues suggests that an automated-shaver may be more suitable. Conflicts of interest: No conflicts of interest. Sources of funding: Part of this work was funded by an Imperial College Research Fellowship for NN and an EPSRC DTP CASE Conversion Studentship for TR (EP/R513052/1)

Aims. The outcome following the development of neurological complications after corrective surgery for scoliosis varies from full recovery to a permanent deficit. This study aimed to assess the prognosis and recovery of major neurological deficits in these patients, and to determine the risk factors for non-recovery, at a minimum follow-up of two years. Methods. A major neurological deficit was identified in 65 of 8,870 patients who underwent corrective surgery for scoliosis, including eight with complete paraplegia and 57 with incomplete paraplegia. There were 23 male and 42 female patients. Their mean age was 25.0 years (SD 16.3). The aetiology of the scoliosis was idiopathic (n = 6), congenital (n = 23), neuromuscular (n = 11), neurofibromatosis type 1 (n = 6), and others (n = 19). Neurological function was determined by the American Spinal Injury Association (ASIA) impairment scale at a mean follow-up of 45.4 months (SD 17.2). the patients were divided into those with recovery and those with no recovery according to the ASIA scale during follow-up. Results. The incidence of major deficit was 0.73%. At six-month follow-up, 39 patients (60%) had complete recovery and ten (15.4%) had incomplete recovery; these percentages improved to 70.8% (46) and 16.9% (11) at follow-up of two years, respectively. Eight patients showed no recovery at the final follow-up. The cause of injury was mechanical in 39 patients and ischaemic in five. For 11 patients with misplaced implants and haematoma formation, nine had complete recovery. Fisher’s exact test showed a significant difference in the aetiology of the scoliosis (p = 0.007) and preoperative deficit (p = 0.016) between the recovery and non-recovery groups. A preoperative deficit was found to be significantly associated with non-recovery (odds ratio 8.5 (95% confidence interval 1.676 to 43.109); p = 0.010) in a multivariate regression model. Conclusion. For patients with scoliosis who develop a major neurological deficit after corrective surgery, recovery (complete and incomplete) can be expected in 87.7%. The first three to six months is the time window for recovery. In patients with misplaced implants and haematoma formation, the prognosis is satisfactory with appropriate early intervention. Patients with a preoperative neurological deficit are at a significant risk of having a permanent deficit. Cite this article: Bone Joint J 2022;104-B(1):103–111

Purpose of study and background. Degeneration of the intervertebral disc is a strong contributor of low back pain. Studies have shown that both, mechanical unloading and overloading, lead to disc degeneration. This is intuitively clear if one considers that an intervertebral disc essentially is a poro-elastic material embedded with cells, which depend on fluid flow for the transport of nutrients and waste products. As such, mechanical loading is also required for regeneration. It is unclear, however, how much loading is beneficial or detrimental for the healthy or degenerated disc. Methods and Results. We developed a loaded disc culture system for the long-term study of disc physiology. This way we could control both the mechanical and biochemical conditions. If no loading was applied, about half of the cells died within a week. Cells died under a low dynamic loading regime after three weeks. A diurnal loading regime rescued cell viability, gene expression profile and mechanical behavior of the discs. Both static and dynamic overloading induced damage to the discs and led to catabolic and inflammatory gene expressions. Conclusion. Intervertebral discs need a certain dosage of mechanical loading to remain viable. Under overloading, cells deform, change gene expression and become degenerative. The matrix is also remodeled, thereby further decreasing the hydrostatic pressure on the cells and increasing their deformation. This induces a vicious circle of disc degeneration, which needs to be reversed in order to repair the disc. The loaded disc culture system also allows evaluating new therapies for disc degeneration. There are no conflicts of interest. Funded by ZonMW program “Alternatives for live animal testing”, grant #11400090;. BioMedical Materials Program, grant # P2.01 IDiDas; Dutch Arthritis Funds, personal grant KSE

Introduction. Musculoskeletal diseases are the biggest cause of morbidity worldwide, with low back pain (LBP) being the leading cause. Forty percent of LBP cases are caused by disease of shock absorbers in the spine known as intervertebral discs (IVDs). The IVDs enable the spine to twist and bend, whilst absorbing load during normal daily activities. The durability of this tissue is sustained by the cells of the spine and so during disease or mechanical damage these cells can behave abnormally further damaging the disc and stimulating local nerves causing extreme pain. Degradation of the intervertebral disc (IVD) currently has no preventative treatment; an injectable hydrogel biomaterial could reinforce disc mechanical properties and promote tissue regeneration. Methods and Results. We present an injectable range of hydrogel biomaterials made from water, clay and polymer that set at 37°C. The materials were made at 80°C polymerised in water and stored at 70°C to remain liquid. The physical properties of the materials were assessed using various methods, including mechanical assessment using temperature-controlled rheometry to monitor the liquid-hydrogel transition. Conclusion. Results showed that by changing three factors within the formulation we can produce a range of materials with suitable mechanical and morphological properties for a variety of tissues of the spine. These types of biomaterials have the potential to provide the first efficacious early-mid stage treatment for IVD disease and reduce the cost of LBP on our health services. Conflicts of interest: CS and CLM are named inventors on the patent for NPgel/BGel. Funded by the Medical Research Council and Versus Arthritis UK: SNiPER

Introduction. Injectable hydrogels via minimally invasive surgery reduce the risk of infection, scar formation and the cost of treatment. Degradation of the intervertebral disc (IVD) currently has no preventative treatment. An injectable hydrogel material could restore disc height, reinforce local mechanical properties, and promote tissue regeneration. We present a hydrogel material Laponite. ®. associated poly(N-isopropylacrylamide)-co-poly(dimethylacrylamide) (NPGel). Understanding how the components of this hydrogel system influence material properties, is crucial for tailoring treatment strategies for the IVD and other tissues. Methods & Results. The effect of hydrogel wt./wt., clay and co-monomer percentages were assessed using a box-Behnken design. Rheometry, SEM, FTIR and swelling was used to measure changes in material properties in simulated physiological conditions. Rheometry revealed gelation temperature of hydrogel materials could be modified with dimethyl-acrylamide co-monomer; however, final maximum mechanical properties remained unaffected. Increasing the weight % and clay % increased resultant mechanical properties from ∼500–2500 G' (Pa), increased viscosity, but retained the ability to flow through a 26G needle at 39°C. Discussion & Conclusions. By increasing the weight and clay percentage of the material we can attain greater mechanical properties, this could be beneficial for orthopaedic or even dental applications. By modifying the co-monomer percentage, we can control gelation temperature important for ensuring the material is fully set at 37°C, this could also be utilised to locally deliver drugs from the implanted material. Our current work is focused on comparing our NPGel material formulation with human IVD tissue. Acknowledgements. We would like to thank Arthritis Research UK grant number 21497 for supporting this research. No conflicts of interest. Sources of Funding: Funded by Arthritis Research UK grant number 21497