Background. Current clinical treatment for spinal instability requires invasive spinal fusion with cages and screw instrumentation. We previously reported a novel injectable hydrogel (Bgel), which supports the delivery and differentiation of mesenchymal stem cells (MSCs) to bone forming cells and supports bone formation in vivo. Here, we investigated whether this system could be utilised to induce bone formation within intervertebral disc tissue as a potential injectable spinal fusion approach. Methodology. Bovine and Human Nucleus pulpous tissue explants were injected with Bgel with and without MSCs. Tissue samples were cultured under hypoxia (5%) in standard culture media for 4 weeks. Cell viability, histological assessment of matrix deposition, calcium formation, and cell phenotype analysis using immunohistochemistry for NP matrix and bone markers. Results. Following injection of B-gel into tissue explants following culture for 4 weeks, cells were visualized within the regions of the B-gel. Demonstrating that native cells were able to migrate into regions of B-gel. Increased collagen deposition was seen in tissue explants injected with Bgel, with increased collagen type I and X but decreased collagen type II staining in explants injected with Bgel. Tissue explants, in the absence of Bgel, showed limited calcium deposition, which was increased in B-gel injected explants. Furthermore, disc cells increased expression of bone markers (alkaline phosphatase & osteocalcin), but decreased NP matrix (Aggrecan and Collagen type II) following Bgel injection. Conclusion. This system could have potential to support spinal fusion via direct injection into the disc. Conflict of interest: C Le Maitre & C Sammon are inventors on the hydrogel discussed. Funding: This work was funded by GrowMed Tech Proof of Concept funding

Introduction. Patients with metastatic spinal cord compression (MSCC) or unstable spinal lesions warrant early surgical consultation. In multiple myeloma, chemotherapy and radiotherapy have the potential to decompress the spinal canal effectively in the presence of epidural lesions. Mechanical stability conferred by bracing may potentiate intraosseous and extraosseous bone formation, thus increasing spinal stability. This study aims to review the role of non-operative management in myeloma patients with a high degree of spinal instability, in a specialist tertiary centre. Methods. Retrospective analysis of a prospectively collected database of 83 patients with unstable myelomatous lesions of the spine, defined by a Spinal Instability Neoplastic Score (SINS) of 13–18. Data collected include patient demographics, systemic treatment, neurological status, radiological presence of cord compression, most unstable vertebral level and presence of intraosseous and extraosseous bone formation. Post-treatment scores were calculated based on follow-up imaging which was carried out at 2 weeks for cord compression and 12 weeks for spinal instability. A paired t-test was used to identify any significant difference between pre- and post-treatment SINS and linear regression was used to assess the association between variables and the change in SINS. Results. A significant reduction in SINS was observed from a pre-treatment average score of 14 to a score of 9, following treatment for myeloma (p<0.001). A higher initial score and a younger age were associated with a larger overall reduction in SINS (p<0.001 and p=0.02 respectively). No single variable (bisphosphates, chemotherapy, radiotherapy and steroids) had a significant association with SINS reduction. 25 (30%) patients had spinal cord compression, all of which showed radiological resolution of cord compression at 2 weeks. No patients developed neurological deterioration during treatment and all patients had an improvement in their pain scores. 64 (77%) patients had evidence of intraosseous and/or extraosseous bone formation on their follow-up scan. Conclusion. Non-operative management in the form of bracing and systemic therapy is a safe and effective treatment for spinal instability and spinal cord compression in myeloma. Treatment of unstable myelomatous lesions of the spine with or without cord compression should not follow traditional guidelines for MSCC. The decision to adopt a non-operative approach in this cohort of patients should ideally be made in a tertiary centre with expertise in multiple myeloma and in a multidisciplinary setting

Introduction. We have developed a new synthetic hydrogel that can be injected directly into the intervertebral disc (IVD) without major surgery. Designed to improve fixation of joint prosthesis, support bone healing or improve spinal fusion, the liquid may support the differentiation of native IVD cells towards osteoblast-like cells cultured within the hydrogel. Here we investigate the potential of this gel system (Bgel) to induce bone formation within intervertebral disc tissue. Methods. IVD tissue obtained from patients undergoing discectomy, or cadaveric samples, were cultured within a novel explant device. The hydrogel was injected, with and without mesenchymal stem cells (MSCs), and cultured under hypoxia, to mimic the degenerate IVD environment, for 4 weeks. Explants were embedded to wax and native cellular migration into the hydrogel was investigated, together with cellular phenotype and matrix deposition. Results. Increased collagen deposition was seen in tissue explants injected with Bgel, with evidence of elevated native cell migration towards the hydrogel. Increased collagen staining was seen in explants injected with Bgel together with MSCs. Alizarin red staining was utilised to investigate calcium deposition. Tissue explants, in the absence of Bgel, showed limited calcium deposition. This was increased in hydrogel-treated samples, with large clumping regions in the tissue that was injected with Bgel and MSCs. Conclusion. The injection of our synthetic hydrogel into disc tissue explants increased the amount of collagen and calcium deposition. This was further enhanced by the incorporation of MSCs, suggesting the promotion of bone formation. Current work is investigating phenotypic markers for bone formation within these tissues. CS and CLM have a patent on the hydrogel system described in this abstract. Funded by EPSRC and Grow MedTech

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. Low back pain is the leading cause of musculoskeletal disease and the biggest cause of morbidity worldwide. Approximately 40% of these are cases are caused by disease of the intervertebral discs (IVDs): the shock absorbing, flexible material located between the bones (vertebrae) along the length of the spine. In severe cases, the spine becomes unstable and it becomes necessary to immobilise or fix the joint in position using a lumbar cage spacer between in the IVD and metal pins with supporting plates in the vertebrae. This is a complex, expensive, major surgery and it is associated with complications, such as spinal fusion failure and inappropriate implant position. These complications have a dramatic impact on the quality of life of the affected patients and the burden to society and the healthcare system is exacerbated. Methods and Results. We present an in vitro study looking at the effect of our Bgel hydrogel on mesenchymal stem cells (MSCs) and their bone forming capacity within lumbar cages: devices used to space the bones apart in the fusion operation, as a mechanism to improve fixation and intra cage bone formation. MSCs were isolated from human hip joint, expanded, seeded within Bgel, cast into well inserts or lumbar cages and cultured for 4 weeks. Using 3D X-ray imaging micro computed tomography (μCT) scans we show that the MSC in the presence Bgel begin to mineralise within the lumbar cages. Histology is currently ongoing and will be presented at the meeting. Conclusion. This study shows the potential to improve current spinal fusion practices with the potential to reduce complications. 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

Purpose of study and background. We have previously reported the development of injectable hydrogels for potential disc regeneration (NPgel) or bone formation which could be utilized in spinal fusion (Bgel). As there are multiple sources of mesenchymal stem cells (MSCs), this study investigated the incorporation of patient matched hMSCs derived from adipose tissue (AD) and bone marrow (BM) to determine their ability to differentiate within both hydrogel systems under different culture conditions. Methods and Results. Human fat pad and bone marrow derived MSCs were isolated from femoral heads of patients undergoing hip replacement surgery for osteoarthritis with informed consent. MSCs were encapsulated into either NPgel or Bgel and cultured for up to 6 weeks in 5% (NPgel) or 21% (Bgel) O. 2. Histology and immunohistochemistry was utilized to determine phenotype. Both fat and bone marrow derived MSCs, were able to differentiate into both cell lineages. NPgel culture conditions increased expression of matrix components such as collagen II and aggrecan and NP phenotypic markers FOXF1 and PAX1, whereas Bgel induced expression of collagen I and osteopontin, indicative of osteogenic differentiation. Conclusion. NPgel and Bgel were able to differentiate patient derived MSCs from different sources into both NP and osteogenic lineages, which may give rise to novel treatment strategies for IVD degeneration and spinal fusion, enabling choice for cell source according to patients' circumstances and needs. C Le Maitre and C Sammon hold a patent for the hydrogel described. Funded by MRC and Versus Arthritis

Aims

To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment.

Aims

Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.

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:. Several reports showed superior fusion rates, as high as 100%, using rhBMP-2 with ALIF cages. This has led to the widespread off-label use of rhBMP-2 in several other lumbar fusion procedures. There is paucity of reports analysing the clinic-radiological outcome of using rhBMP-2 to promote bone union in cases of symptomatic pseudoarthosis following lumbar spine fusion. Methods:. 52 consecutive patients who underwent revision spinal surgery for symptomatic pseudoarthosis utilizing rhBMP-2 between 2008 and 2013 were included in the study. Demographic, and surgical data were collected from medical records. Functional outcomes were recorded using the ODI. All patients had preoperative fine-cut CT scan to confirm pseudoarthosis. Postoperative CT-scan at 6 months was routinely done to confirm fusion. Results:. Average age at time of revision surgery was 54years (range 28–73). Average follow up was 3 years 5 months (range 2–5 years). Overall fusion rate of 92.3% (48/52) was achieved. The average ODI has improved from 56% preoperatively to 49% postoperatively. We had 1 infection case, and 5 complications related to metalwork. One case with neuronal complications was recorded. No rhBMP-2 related complications. There was no record of heterotopic bone formation in the spinal canal or the neuroforamen. Conclusion:. Recombinant BMP-2 is a safe and effective adjunct to revision lumbar spinal fusion surgery to alleviate back pain symptoms from pseudoarthosis. The limitations of the study include: retrospective review, lack of matched cohort utilising iliac crest bone graft, and relatively short follow-up

To evaluate and describe the plain radiographic changes observed with time in fusions using SiS-CaP. We describe, for the first time, 4 stages of bone substitute fusion mass (BSFM) radiographic appearance in relation to time post-op. Retrospective, radiological evaluation. Over 200 plain radiographs were evaluated. 70 consecutive fusions for degenerative spinal stenosis were included, in all cases performed by the same surgeon using the same operative technique. Follow-up was from 3 months to 2 years post-op. Radiographs were evaluated for the presence or absence of SiS-CaP granules, bone formation and for evidence of pseudarthrosis. Trends were seen within the BSFM with respect to time. At 6-12 weeks post-op a ‘homogenous granular stage’ indicates the presence of the unchanged SiS-CaP. At 12 weeks, small pockets appear within the BSFM in the ‘vacuolation stage’, indicating bioresorption of the graft. Vacuoles become increasingly radio-opaque indicating bone proliferation during the ‘homogenous lamellar stage’. At variable time between 6 months and 2 years, the BSFM becomes encapsulated in the ‘cortication stage’ visible as a sclerotic rim around the BSFM. We have seen a clear trend in the behaviour of the fusion mass in this case series. The radiological stages we have described above can be closely correlated with previously reported in-vitro and in-vivo studies looking at the micro-function of SiS-CaP. We hope that this description will help to judge the progress of graft incorporation and fusion. Further study of inter and intra-observer correlation will be required

To assess radiological fusion rates in posterolateral fusions using SiS-CaP. Retrospective, radiological follow-up study. Single surgeon series of 76 consecutive patients were evaluated, in a regional spinal unit. All patients had clinical and radiological (MRI) spinal canal stenosis secondary to degenerative spondylosis or spondylolisthesis. Surgery consisted of instrumentation, decompression and meticulous preparation of the posterolateral graft bed by removal of all soft tissues posterior to the inter-transverse membrane and decortication of transverse processes (TPs). SiS-CaP putty was injected into this gutter and moulded around the instrumentation. Good quality, well prepared bone chips from the posterior decompression were seeded into the putty. Patient radiographs were reviewed at 3-6 months, 1 year and 2 years. Radiographs were assessed using a protocol to examine granularity, bone formation and evidence of pseudarthrosis, based upon previously reported literature . 1. and our personal experience. Of the 76 patients, 26 were excluded. M:F was 21:29. Mean age was 58yrs. Average number of motion segments fused per case was 2.2. There was one pseudarthrosis with metalwork fracture, and thus a total fusion rate of 98%. In addition, one patient had scanty bridging of TPs, and one patient had lucency around the S1 screws. SiS-CaP, as a bone graft substitute in posterolateral instrumented fusions, gives comparable results to published fusion rates using autologous iliac crest grafting and/or Bone Morphogenic Protein . 2. Moreover, it avoids the associated morbidity of iliac bone harvest

Background. For bone grafting procedures, the use of autologous bone is considered the gold standard, as it is has a better healing capacity compared to other alternatives as allograft and synthetic bone substitutes. However, as there are several drawbacks related to autografting (infection, nerve- or vascular damage, chronic pain problems, abdominal herniation), there has been a targeted effort to improve the healing capacities of synthetic bone substitutes. Aim. To evaluate the performance of a carbonated osteoionductive hydroxyapatite (CHA) scaffold of clinical relevant size (Ø=15mm, H=50mm) in a sheep model of multi level posterolateral intertransverse lumbar spine fusion after activation with autologous bone marrow nuclear cells (BMNC) in a flow perfusion bioreactor. Method. Two groups were included in the study, autograft (n=6) and CHA scaffold (n=6) CHA. A paired design was used between and within the groups as lumbar posterolateral arthrodesis was performed in sheep on two levels (L2-L3, L5-L6) +/− BMNC, respectively. Before implantation, the CHA scaffold was cultured in a flow perfusion bioreactor system with BMNC for 21 days, and the autograft group was supplemented with isolated BMNC during the procedure. Micro tomography was used to evaluate fusion rate and the microarchitectural properties of the explants after an observation period of four months. Results. In the autograft group, the healing rate was 83.3% irrespective of the presence BMNC, and in the CHA group, 66.7% fused in the presence of BMNC, and 33.3% without. The microarchitectural data suggested the autograft group to be superior to the CHA scaffold regarding mechanical properties, however porosity decreased significantly (p=0.001) in the CHA scaffold group suggesting deposition of mineralized bone matrix. Conclusion. Based on the fusion rate and micro architectural properties, we consider the CHA scaffold fully capable of new bone formation, and that the presence of BMNC has a positive effect on the fusion rate in a challenging model of bone healing

Objectives

Pulsed electromagnetic field (PEMF) stimulation was evaluated after anterior cervical discectomy and fusion (ACDF) procedures in a randomized, controlled clinical study performed for United States Food and Drug Administration (FDA) approval. PEMF significantly increased fusion rates at six months, but 12-month fusion outcomes for subjects at elevated risk for pseudoarthrosis were not thoroughly reported. The objective of the current study was to evaluate the effect of PEMF treatment on subjects at increased risk for pseudoarthrosis after ACDF procedures.

Aims

Patients with multiple myeloma (MM) develop deposits in the spine which may lead to vertebral compression fractures (VCFs). Our aim was to establish which spinopelvic parameters are associated with the greatest disability in patients with spinal myeloma and VCFs.

Aims

The aims of this study were to evaluate the clinical and radiological outcomes of instrumented posterolateral fusion (PLF) performed in patients with rheumatoid arthritis (RA).

The presacral retroperitoneal approach for axial lumbar interbody fusion (presacral ALIF) is not widely reported, particularly with regard to the mid-term outcome. This prospective study describes the clinical outcomes, complications and rates of fusion at a follow-up of two years for 26 patients who underwent this minimally invasive technique along with further stabilisation using pedicle screws. The fusion was single-level at the L5-S1 spinal segment in 17 patients and two-level at L4–5 and L5-S1 in the other nine. The visual analogue scale for pain and Oswestry Disability Index scores were recorded pre-operatively and during the 24-month study period. The evaluation of fusion was by thin-cut CT scans at six and 12 months, and flexion-extension plain radiographs at six, 12 and 24 months. Significant reductions in pain and disability occurred as early as three weeks postoperatively and were maintained. Fusion was achieved in 22 of 24 patients (92%) at 12 months and in 23 patients (96%) at 24 months. One patient (4%) with a pseudarthrosis underwent successful revision by augmentation of the posterolateral fusion mass through a standard open midline approach.

There were no severe adverse events associated with presacral ALIF, which in this series demonstrated clinical outcomes and fusion rates comparable with those of reports of other methods of interbody fusion.

We carried out a prospective study to determine whether the addition of a recombinant human bone morphogenetic protein (rhBMP-2) to a machined allograft spacer would improve the rate of intervertebral body fusion in the spine. We studied 77 patients who were to undergo an interbody fusion with allograft and instrumentation. The first 36 patients received allograft with adjuvant rhBMP-2 (allograft/rhBMP-2 group), and the next 41, allograft and demineralised bone matrix (allograft/demineralised bone matrix group). Each patient was assessed clinically and radiologically both pre-operatively and at each follow-up visit using standard methods. Follow-up continued for two years.

Every patient in the allograft/rhBMP-2 group had fused by six months. However, early graft lucency and significant (> 10%) subsidence were seen radiologically in 27 of 55 levels in this group. The mean graft height subsidence was 27% (13% to 42%) for anterior lumbar interbody fusion, 24% (13% to 40%) for transforaminal lumbar interbody fusion, and 53% (40% to 58%) for anterior cervical discectomy and fusion. Those who had undergone fusion using allograft and demineralised bone matrix lost only a mean of 4.6% (0% to 15%) of their graft height.

Although a high rate of fusion (100%) was achieved with rhBMP-2, significant subsidence occurred in more than half of the levels (23 of 37) in the lumbar spine and 33% (6 of 18) in the cervical spine. A 98% fusion rate (62 of 63 levels) was achieved without rhBMP-2 and without the associated graft subsidence. Consequently, we no longer use rhBMP-2 with allograft in our practice if the allograft has to provide significant structural support.