Costoplasty remains useful in the treatment of adolescent idiopathic scoliosis, rib hump and associated chest wall deformities. However traditional costoplasty increases morbidity and blood loss. We examine the feasibility and possible effectiveness of a more conservative costoplasty using an animal model. 4 fresh half Ovine rib cages from separate animals were obtained, stored at +4 °C and warmed to room temperature before testing. Each rib cage was randomly assigned to group 1, 2, 3 or 4. Ribs 2–10 were dissected out for testing. The ribs then underwent stepwise deconstruction according to their group. Beginning at the convexity, removing first the convex cortex, then the cancellous, then the cranial and caudal cortices to leave just the concave cortex. Testing for stiffness was by three-point bending on the concave side of each rib with the rib fixed at the head of the rib and 5 cm from the resected area. The ribs were deformed at a constant rate of 0.5 mm.sec . −. 1 up to a maximum load of 9.99 kg or until fracturing. Then stress was plotted against strain to find the Young's modulus of each group and statistics carried out with an ANOVA test. The ribs in each group were as follows: Group 1= control, group 2= 30 mm long convex side cortical bone removed 10 mm from lateral tubercle, group 3= convex, cortical and cancellous bone removal and group 4= removal of convex, caudal and cranial cortices with cancellous removal. The Young's Modulus of the groups were: 1= 3.38 N-m (+/− 0.84), 2= 2.65 N-m (+/− 1.58), 3= 1.55 N-m (+/− 0.55) and 4= 0.74 N-m (+/− 0.55). Groups 3 and 4 were significantly less stiff than group 1 (p< 0.01.) No ribs in groups 1, 2 and 4 fractured under the maximum load. 5/8 ribs in group 3 fractured before the maximum load was administered. By deconstructing the rib down to only the concave side it becomes significantly more flexible by approximately 4.5 times than the control Ribs. Coupled with its increase in flexibility it still retains its ability to withstand up to 10 kg of load without fracture. It may be possible to perform a costoplasty whilst preserving ventilatory integrity. This may improve rib hump correction, and curve correction due to increased flexibility of the stiff thoracic cage

Introduction. The response of the intervertebral disc to asymmetric forces may accelerate degeneration through changes in the matrix. Macroscopically, the disc sustains structural changes that may play a part in the progression of a scoliotic curve. Molecularly, disc degeneration is the outcome of the action of matrix metalloproteases (MMPs), members of a family of enzymes that bring about the degradation of extracellular matrix components. In this study we measured in vivo the expression of MMPs in a rat scoliotic intervertebral disc and studied the effect of the degree of the deformity on their production. Methods. Asymmetric forces were applied in the intervertebral disc between the ninth and tenth vertebrae at the base of a rat tail with the use of a mini Ilizarov external fixator, under anaesthesia. Animals were categorised into three groups according to the degree of the deformity. In group I, the deformity that was applied on the intervertebral disc was 10°, in group II 30°, and in group III 50°. All the animals used were female Wistar rats before adulthood, to take into account the effect of growth for the study of intervertebral disc changes. The intact intervertebral discs outside the fixator were used as controls. After the rats' death on day 35, the tails were prepared and analysed with an immunohistochemical protocol for chromogenic detection and location of MMPs 1 and 12 in tissue sections of the intervertebral discs. Results. We recorded an increase of the concentration of the MMPs in all groups compared with controls. The quantity of the MMPs increased as the degree of the deformity progressed. MMPs were detected mainly in fibrocartilage cells of the degenerative part, which were formed as result of the compression forces. We detected a differentiation of a large number of disc cells into chondrocytes at the transitional zone of the intervertebral disc adjacent to the vertebral end plates. Conclusions. The application of asymmetric forces on the intervertebral discs of a rat tail results in an increase of MMP expression in the disc cells. The amount of MMPs produced is proportional to the degree of the deformity and has an asymmetrical pattern of distribution into the intervertebral disc

Aims. To systematically evaluate whether bracing can effectively achieve curve regression in patients with adolescent idiopathic scoliosis (AIS), and to identify any predictors of curve regression after bracing. Methods. Two independent reviewers performed a comprehensive literature search in PubMed, Ovid, Web of Science, Scopus, and Cochrane Library to obtain all published information about the effectiveness of bracing in achieving curve regression in AIS patients. Search terms included “brace treatment” or “bracing,” “idiopathic scoliosis,” and “curve regression” or “curve reduction.” Inclusion criteria were studies recruiting patients with AIS undergoing brace treatment and one of the study outcomes must be curve regression or reduction, defined as > 5° reduction in coronal Cobb angle of a major curve upon bracing completion. Exclusion criteria were studies including non-AIS patients, studies not reporting p-value or confidence interval, animal studies, case reports, case series, and systematic reviews. The GRADE approach to assessing quality of evidence was used to evaluate each publication. Results. After abstract and full-text screening, 205 out of 216 articles were excluded. The 11 included studies all reported occurrence of curve regression among AIS patients who were braced. Regression rate ranged from 16.7% to 100%. We found evidence that bracing is effective in achieving curve regression among compliant AIS patients eligible for bracing, i.e. curves of 25° to 40°. A similar effect was also found in patients with major curve sizes ranging from 40° to 60° when combined with scoliosis-specific exercises. There was also evidence showing that a low apical vertebral body height ratio, in-brace correction, smaller pre-brace Cobb angle, and daily pattern of brace-wear compliance predict curve regression after bracing. Conclusion. Bracing provides a corrective effect on scoliotic curves of AIS patients to achieve curve regression, given there is high compliance rate and the incorporation of exercises. Cite this article: Bone Joint J 2024;106-B(3):286–292

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In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc. Cite this article: Bone Joint Res 2013;2:169–78

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To report the development of the technique for minimally invasive lumbar decompression using robotic-assisted navigation.

Aims

The aim of this study was to investigate the incidence and characteristics of instrumentation failure (IF) after total en bloc spondylectomy (TES), and to analyze risk factors for IF.

To assess the effectiveness of unilateral sublaminar and concave rib tethering with convex rib resection through the period of peak growth in lambs. Morphometric growth data from 10 experimental Scottish Blackface sheep were compared to those from 5 control animals (no intervention) over 12 months. Standardized AP and Lateral radiographs were taken before and at monthly intervals after scoliosis creation. The Cobb angle was measured in the coronal and sagittal planes. Rotational mal-alignment was assessed by axial CT 7 months post surgery. In the supine position the control animals had no coronal plane deformity and a mean 5° lordosis (T4-T12). These figures did not alter with growth (doubling of body weight). Tethering (at age 5 weeks) produced an immediate scoliosis of 22±11° and a lordosis of 24±8° (means(sd). The degree of scoliosis was maintained over 7 months (at 20°) but lordosis increased (to 59±11°, p<0.01). There was an associated change in vertebral rotation. Surgery had no influence on rate of growth or animal development. Two animals died from Clostridium associated enterocolitis. There were no deaths associated with the surgical intervention. This ovine model gives a progressive spinal deformity in the sheep but primarily in the sagittal plane. This fact should be considered in studies designed to evaluate the effectiveness of surgical implants

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

Purpose of study and background. Low back pain affects 80% of the population at some point in their lives with 40% of cases attributed to intervertebral disc (IVD) degeneration. A number of potential regenerative approaches are under investigation worldwide, however their translation to clinic is currently hampered by an appropriate model for testing prior to clinical trials. Therefore, a more representative large animal model for IVD degeneration is needed to mimic human degeneration. Here we investigate a caprine IVD degeneration model in a loaded disc culture system which can mimic the native loading environment of the disc. Methods and Results. Goat discs were excised and cultured in a bioreactor under diurnal, simulated-physiological loading (SPL) conditions, following 3 days pre load, IVDs were degenerated enzymatically for 2hrs and subsequently loaded for 10 days under physiological loading. A PBS injected group was used as controls. Disc deformation was continuously monitored and changes in disc height recovery quantified using stretched-exponential fitting. Histological staining was performed on caprine discs to assess extracellular matrix production and immunohistochemistry performed to determine expression of catabolic protein expression. The injection of collagenase and cABC induced mechanical behavior akin to that seen in human degeneration. A decrease in collagens and glycosaminoglycans (GAGs) was seen in enzyme injected discs, which was accompanied by increased cellular expression for degradative enzymes and catabolic cytokines. Conclusion. This model provides a reproducible model of IVD degeneration which mimics human degeneration. This model allows the testing of biomaterials and other potential treatments of IVD degeneration on a scale more representative of the human disc. There are no conflicts of interest. Funded by MRC and Versus Arthritis

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

We evaluated the efficacy of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) in a mini-pig model of spinal anterior interbody fusion. A total of 14 male mini-pigs underwent three-level anterior lumbar interbody fusion using polyether etherketone (PEEK) cages containing porous hydroxyapatite (HA). Four groups of cages were prepared: 1) control (n = 10 segments); 2) 50 μg E-BMP-2 (n = 9); 3) 200 μg E-BMP-2 (n = 10); and 4) 800 μg E-BMP-2 (n = 9). At eight weeks after surgery the mini-pigs were killed and the specimens were evaluated by gross inspection and manual palpation, radiological evaluation including plain radiographs and micro-CT scans, and histological analysis. Rates of fusion within PEEK cages and overall union rates were calculated, and bone formation outside vertebrae was evaluated. One animal died post-operatively and was excluded, and one section was lost and also excluded, leaving 38 sites for assessment. This rate of fusion within cages was 30.0% (three of ten) in the control group, 44.4% (four of nine) in the 50 μg E-BMP-2 group, 60.0% (six of ten) in the 200 μg E-BMP-2 group, and 77.8% (seven of nine) in the 800 μg E-BMP-2 group. Fusion rate was significantly increased by the addition of E-BMP-2 and with increasing E-BMP-2 dose (p = 0.046). In a mini-pig spinal anterior interbody fusion model using porous HA as a carrier, the implantation of E-BMP-2-loaded PEEK cages improved the fusion rate compared with PEEK cages alone, an effect that was significantly increased with increasing E-BMP-2 dosage. Cite this article: Bone Joint J 2013;95-B:217–23

Introduction. Spinal deformations are a deviation of the natural arrangement of forces during growth. Environmental factors play a part in these deviations. The presence of lordosis in the thoracic spine is a causative factor in spinal deformations that needs to be addressed. Most biomechanical models of bracing have a scientific background. Has older knowledge lost its value? In living structures, all processes such as regulation of equilibrium in posture and movement use Newton's law and extended laws of Hooke for conservation of energy, momentum, and angular momentum under control of the central nervous system. Form follows function (phylogenetic and ontogenetic) in the spine as primary engine in movement in animals. The change in function in bipedals is that the coupling mechanism at the thoracolumbar joint now couples a reversed pendulum. Methods. A literature search shows a clear gap in the evolution in science on deformities during 1914–45. In 1792, Van Gesscher postulated two concepts in Observations on Deformations of the Spine (Dutch). First, the optimalisation of the balancing forces in men needs a specific optimum curvature to keep the weight of the head and shoulders above the hips. The second concept was the role of sitting in relation to changes around the discs at the thoracolumbar spine. Girls who read or knitted while sitting developed scoliosis more easily than did others. His extending (by lordosis) corrective corset was used for more than 150 years before plaster became popular. Andry described guidance and correction of growing spines with use of the moulding capability of muscular forces, with exercises and extending corsets (for so-called weak girls). Extension and avoidance of incorrect posture during sitting became a mainstay in orthopaedics (and schools). In 1907, Wullstein described experiments in young dogs to show how forced fiexion produces all characteristics of kyphotic deformities. In 1912, Murk Jansen did a critical review of all available knowledge and his own research in The Physiologic Scoliosis and its causes. Post mortem studies showed anatomical asymmetry in the left and right crura of the diaphragm, which indicated that asymmetric rotational forces in ventilation could induce predominant lateral curves. In-vivo tests show increased thoracolumbar kyphosis if siblings are put in seated positions too frequently and too soon. The stiffening in kyphosis creates a fulcrum to cantilever the opposing rotational forces to lateral curvatures. In experiments in rabbits, lower intrathoracic pressure was shown in the right pleural cavity. Common alertness of parents and teachers was underwritten. Some of this still survives. In progressed scoliosis, Sayre's method of corrective plastering in suspension and Calot's corrections in prone position under anaesthesia and plaster shelves with lordosis in bed became popular. In the Volkmann Hueter principle, the resilience of the deformable structures in the spine were identified–eg, the discs, the apophyses, and the cartilage in joints have a role in spinal deformity. Cobb drew attention to the clinical aspects of scoliosis. Roth provided a comprehensive explanation of how growth is organised and regulated by the oldest organ of animal life: the central nervous system in vertebrates. Between 1960 and 1985, Roth developed his concepts on neurovertebral and neuro-osseous growth relations and the tension-driven incongruence of growth. Roth provided new biological knowledge about how growth seems to support older clinical observations. In animal experiments, mechanical modelling, and radiological studies in scoliosis he stressed the role that growth has in the formation of the spine. A so-called short cord can indeed cause scoliosis. Recent studies with MRI in idiopathic scoliosis confirm this hypothesis. Personal observations In 2008, a study showed that forceful restoration of thoracolumbar lordosis can correct double major scoliotic curves. A consequent thoracolumbar kyphotic curve was found, and recently reproduced. The thoracolumbar lordotic intervention brace technique showed promising results. It relied on the older techniques, leaving only the fear for lordosis brought by Dickson. In personal observations, the presence of neuromuscular tightness or tension also present in progressive scoliosis as representatives of deforming and protective forces. Conclusions. Previous knowledge depicts spinal growth as result of a combination of neuro-osseous growth regulation in a very complex but understandable loco-motor system, in which external factors cause muscular reaction that obey all mechanical laws. Lifestyle factors seem to greatly affect deformations

Background. We have reported an injectable L-pNIPAM-co-DMAc hydrogel with hydroxyaptite nanoparticles (HAPna) which promotes mesenchymal stem cell (MSC) differentiation to bone cells without the need for growth factors. This hydrogel could potentially be used as an osteogenic and osteoconductive bone filler of spinal cages to improve vertebral body fusion. Here we investigated the biocompatibility and efficacy of the hydrogel in vivo using a proof of concept femur defect model. Methods. Rat sub-cut analysis was performed to investigate safety in vivo. A rat femur defect model was performed to evaluate efficacy. Four groups were investigated: sham operated controls; acellular L-pNIPAM-co-DMAc hydrogel; acellular L-pNIPAM-co-DMAc hydrogel with HAPna; L-pNIPAM-co-DMAc hydrogel with rat MSCs and HAPna. Following 4 weeks, defect site and organs were histologically examined to determine integration, repair and inflammatory response, as well as Micro-CT to assess mineralisation. Results. No inflammatory reactions or toxicity were seen in any animal. Enhanced bone healing was observed in aged exbreeder female rats where hydrogel was injected with increased deposition of collagen type I. Integration of the hydrogel with surrounding bone was observed without the need for delivered MSCs; native cell infiltration was also seen and bone formation was observed within all hydrogel systems investigated. Conclusion. This novel hydrogel is biocompatible, facilitates migration of cells, promotes increased bone formation and integrates with surrounding bone. This system could be injected to fill spaces within and surrounding spinal cages to aid in cage fixation and spinal fusion without the need for harvesting of bone autografts, thus reducing operative risk and surgical cost. Conflicts of Interest: None. Source of Funding: BMRC, MERI Sheffield Hallam University

Introduction. We prospectively examined the effect of pedicle screw placement at a young age (<5 years) for early-onset spinal deformity on the growth and development of pedicles and the spinal canal. Methods. Patients with early-onset deformity who received pedicle screw placement before the age of 5 years and had preoperative and final follow-up axial imaging were included. To increase sample size, patients who had the same criteria but with no preoperative axial images were also included. Anteroposterior and transverse diameters of the canal and pedicle length were measured on axial images cutting through the middle of the pedicle (figures 1 and 2). Results. 13 patients (five male, eight female) met inclusion criteria. Average age at surgery was 46·6 months (29–60), and average follow-up 49·8 months (24–82). 77 instrumented and 32 non-instrumented levels were studied. The table summarises measurements. In the nine patients without preoperative axial imaging, pedicle lengths and canal diameters seemed to accord with previously published normative morphological data for this age group. Conclusions. Animal studies have shown the potential slowing of pedicle and canal growth in immature spines with pedicle screws. This is the first study to examine the behaviour of instrumented immature human vertebrae prospectively. Early application of pedicle screws does not seem to cause adverse effects on pedicle and canal growth in young patients. This discordance between human and animal studies may have three explanations: (1) although the neurocentral cartilage is still visible it may not be physiologically active in this age group; (2) a single screw across may not exert sufficient compression; (3) or the canal may have means of remodelling that is yet not known

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Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

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Spinal fusion remains the gold standard in the treatment of idiopathic scoliosis. However, anterior vertebral body tethering (AVBT) is gaining widespread interest, despite the limited data on its efficacy. The aim of our study was to determine the clinical efficacy of AVBT in skeletally immature patients with idiopathic scoliosis.

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Spinal deformity surgery carries the risk of neurological injury. Neurophysiological monitoring allows early identification of intraoperative cord injury which enables early intervention resulting in a better prognosis. Although multimodal monitoring is the ideal, resource constraints make surgeon-directed intraoperative transcranial motor evoked potential (TcMEP) monitoring a useful compromise. Our experience using surgeon-directed TcMEP is presented in terms of viability, safety, and efficacy.

AO Spine Reference Centre & Institute of Health & Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. Traumatic spinal cord injury (SCI) is a devastating condition with no curative therapy. Pro-inflammatory therapy has been suggested recently to try and reduce the inhibitory glial scar and promote neural regeneration and healing. The aim of this study is to investigate the potential of sustained delivery of angiogenic/pro-inflammatory growth factors to reduce the secondary degeneration after spinal cord injury. Adult male Wistar Kyoto rats (200-300g; 12-16weeks old) were subjected to cord hemisections via a T10 laminectomy. Animals were randomised to treatment or control groups after the spinal cord injury had been induced. Treatment consisted of implantation of a mini-osmotic pump capable of delivering 5 micrograms vascular endothelial growth factor (VEGF) and 5 micrograms platelet-derived growth factor (PDGF), via a catheter, to the site of the lesion, over 7 days(n=6). Control animals were subjected to either cord lesion only (n=6) or lesion plus mini-pump delivering PBS (phosphate-buffered saline) solution (n=6). Rats were sacrificed at one month and the spinal cords were harvested and examined by immunohistology, using anti-neurofilament-200 and anti-Glial Acidic Fibrillary Acidic Protein (GFAP) antibodies. RESULTS: Active treatment spinal cords showed a higher level with aboration of the axonal filament through the defect and more dense neurofilament-200 staining at the lesion site compared to both control groups. The treatment also showed the elevated presence of activated microglia in the lesion, whilst distal to the lesion the microglia and astrocytes retained an unreactive phenotype. Pro-inflammatory therapy in the rat spinal cord-injury model showed favourable histological findings after sustained delivery of PDGF and VEGF

Introduction. Adolescent idiopathic scoliosis (AIS) is the most common paediatric spinal deformity, affecting about 3% of school-aged children worldwide. This disorder occurs in otherwise healthy children who bear no obvious deficiencies in the components of the spinal column itself. The cause of AIS is poorly understood, as is implied by the name. Lesions of the bony composition of the vertebrae, the vertebral endplates, the paraspinous muscles, or the neurological system each have been proposed to explain disease pathogenesis. Progress has been hampered by the absence of an obvious AIS animal model. Consequently we have used genetic studies in human populations to identify factors underlying AIS susceptibility. The complex inheritance and population frequency of AIS suggest that many genetic factors are involved in this disease. To search comprehensively for such factors we previously undertook the first genome-wide association study (GWAS) of AIS susceptibility in a cohort of 419 families in Texas, USA. We found that chromosome 3 SNPs in the proximity of the CHL1 gene yielded strongest results, which we replicated in additional cohorts (rs10510181 OR 1·49, 95% CI 1·29–173, p=2·58×10–8). CHL1 is of interest because it encodes an axon guidance protein and is functionally related to the ROBO3 gene that causes hereditary gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Here we expanded the study to 702 Texas families. Methods. We tested more than 327 000 single-nucleotide polymorphisms (SNPs) across all human autosomes for association with disease. Results. Results of the study in 702 Texas families yielded evidence for association with SNPs in a second axon guidance gene, DSCAM, which encodes a protein in the same structural and functional class with Chl1 and Robo3 (rs2222973 combined OR 0·59, 95% CI 0·48–0·74; p=1·46×10–6). We additionally found AIS associations with loci in CNTNAP2, whose protein product interacts directly with L1 and Robo class proteins and participates in axon pathfinding. Conclusions. These data support genetic variation in axon guidance genes as risk factors in AIS. Our results provide new insight into disease pathogenesis and suggest that late-onset scoliosis may be correlated with secondary neurological development