Background. Chronic low back pain is strongly linked to degeneration of the intervertebral disc (IVD), which currently lacks any targeted treatments. This study explores NPgel, a biomaterial combined with notochordal cells (NC), developmental precursor cells, as a potential solution. NCs, known for anti-catabolic effects on IVD cells, present a promising avenue for regenerating damaged IVD tissue. Methods. Bovine IVDs underwent enzymatic degeneration before NPgel (+/- NC) injection. Degenerated bovine IVDs were cultured under biomechanical loading for 21 days. Histology and immunohistochemistry assessed NC survival, phenotype, and matrix production. Within an in vivo sheep pilot study, NPgel (+/- NC) was injected into degenerated IVDs, blood was taken, and immune cell activation was monitored via flow cytometry over three months post-injection. Results. Within the ex vivo model, IVDs injected with NPgel (+/- NC) exhibited increased matrix expression and deposition. Viable NCs were detected post-culture, indicating survival and matrix production. In the in vivo model, NPgel injection into sheep IVDs did not significantly increase activation of immune cells compared to controls, suggesting no systemic inflammatory effects. Conclusion. NPgel, combined with NCs, shows promise for IVD regeneration. Ex vivo findings indicate NPgel supports NC survival and matrix production. Moreover, in vivo results demonstrate the absence of systemic immunogenic responses post-NPgel injection. This suggests NPgel's potential as a carrier for NCs in IVD regeneration therapy. These findings underscore NPgel's candidacy for further investigation in addressing chronic low back pain associated with IVD degeneration. Subsequent research, including long-term efficacy and safety evaluations, is imperative for clinical translation. Conflicts of interest. There are no conflicts of interest. Sources of funding. iPSpine, grant # 825925, Horizon 2020

Objectives. Low back pain is strongly associated with degeneration of the intervertebral disc (IVD). During degeneration, altered matrix synthesis and increased matrix degradation, together with accompanied cell loss is seen particularly in the nucleus pulposus (NP). It has been proposed that notochordal (NC) cells, embryonic precursors for the cells within the NP, could be utilized for mediating IVD regeneration. However, injectable biomaterials are likely to be required to support their phenotype and viability within the degenerate IVD. Therefore, viability and phenotype of NC cells were analysed and compared within biomaterial carriers subjected to physiological oxygen conditions over a four-week period were investigated. Methodology. Porcine NC cells were incorporated into three injectable hydrogels: NPgel (a L-pNIPAM-co-DMAc hydrogel), NPgel with decellularized NC-matrix powder (dNCM) and Albugel (an albumin/ hyaluronan hydrogel). The NCs and biomaterials constructs were cultured for up to four weeks under 5% oxygen (n=3 biological repeats). Histological, immunohistochemical and glycosaminoglycans (GAG) analysis were performed to investigate NC viability, phenotype and extracellular matrix synthesis and deposition. Results. Histological analysis revealed that NCs survive in the biomaterials after four weeks and maintained cell clustering in NPgel, Albugel and dNCM/NPgel. NPgel and Albugel maintained NC cell markers and extracellular matrix. NC containing constructs excreted more GAGs over the four weeks than the acellular controls. Conclusion. NC cells maintain their phenotype and characteristic features in vitro when encapsulated into biomaterials. NC cells and biomaterial construct could potentially become a therapy to treat and regenerate the IVD. Conflicts of interest: No conflicts of interest. Sources of funding: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 825925

Introduction. Intervertebral disc degeneration (IVDD) associated with low back pain is a major contributor to global disability. Current treatments are poorly efficient in the long-term resulting in medical complications. Therefore, minimally invasive injectable therapies are required to repopulate damaged tissues and aid regeneration. Among injectable biomaterials, self-assembling peptide hydrogels (SAPHs) represent potential candidates as 3D cell carriers. Moreover, the advent of graphene-related materials has opened the route for the fabrication of graphene-containing hydrogel nanocomposites to direct cellular fate. Here, we incorporated graphene oxide (GO) within a SAPH to develop a biocompatible and injectable hydrogel to be used as cell carrier to treat IVDD. Methods and results. Hydrogel morphology and mechanical properties have been investigated showing high mechanical properties (G'=12kPa) comparable with human native nucleus pulposus (NP) tissue (G'=10kPa), along with ease of handling and injectability in dry and body fluid conditions. Hydrogel nanocomposites resulted biocompatible for the encapsulation of bovine NP cells, showing higher viability (>80%) and metabolic activity in 3D cell culture over 7 days, compared to GO-free hydrogels. Moreover, GO has demonstrated to bind TGF-β3 biomolecules with high efficiency, suggesting the use of GO as local reservoir of growth factors within the injected hydrogel to promote extracellular matrix deposition and tissue repair. Conclusions. Our results show that incorporation of GO within the SAPH improves cell viability and metabolic activity. Furthermore, its tissue-mimicking mechanical properties and chemical tunability make it a promising candidate as injectable carrier of NP cells for the treatment of IVDD. Part of this work has been published (DOI: 10.1016/j.actbio.2019.05.004). Conflicts of interests: No conflicts of interest. Sources of funding: The authors thank the EPSRC & MRC CDT in Regenerative Medicine for its financial support (EP/L014904/1)

Introduction. Research has suggested baby wearing results in happier healthier babies [1]. Various designs of carrier are available, is there one which has less impact on the biomechanics of the cervical spine?. Methods. 18 volunteers (9 male and female) performed a warm up procedure on the neck (movement through each range of motion), repeated thrice. Measurement of the active cervical range of motion (ACROM) in flexion and extension using a Cervical Range of Motion device, described in previous studies [2]. Volunteers were then allocated a baby carrier to wear including a specially designed “baby” mannequin (dimensions based on population average statistics for a 1yro). Volunteers continued with ADLs, returning after 2 hours. With the carrier removed, measurements were repeated (without warm-up). Volunteers were assessed at the same time of day, thrice (control, single carrier, double carrier) with at least 1 day between carrying. Results. ACROM measurements following the use of either single or double shoulder carrier, or no carrier showed through a paired t-test significance of <0.02, found a change from post-stretching to post-carrying in those wearing the single shoulder carrier, this was the only test period to result in a decrease in both extension and total ACROM for flexion-extension. Conclusions. Carrying an average 1 yro using a single shoulder carrier can lead to accelerated rate of change in extension of ACROM. These results may have an implication to healthy bodies, thus highly likely that choice of carrier in those with extant cervical spine dysfunction might lead to exacerbation of the problems and pain. Conflicts of interest: No conflicts of interest. Sources of funding: No funding obtained

Aims

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.

Aims

Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

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. Idiopathic scoliosis is a spine disorder of unknown origin with a prevalence of 1·5-3% in the general population. Apart from the large multifactorial form sample of idiopathic scoliosis, there is a good evidence for the existence of a monogenic subgroup in which the disease is inherited in a dominant manner. However, results from published work suggest a strong heterogeneity in locations of the mutated genes. Methods. With a high resolution genome-wide scan, we undertook linkage analyses in three large multigenerational families with idiopathic scoliosis compatible with dominant inheritance, including 11–12 affected members or obligate carriers. Results. In two of these families, our results suggested intrafamilial genetic heterogeneity, whereas in the other we recorded a perfect marker disease co-segregation in two distinct chromosomal regions. We can state that one of these two locations is a novel idiopathic scoliosis disease gene locus, since the probability of having by chance this perfect co-segregation twice in the genome is very low (p=0·001). Lastly, in all three families studied, we excluded compatibility with linkage to the previously mapped dominant idiopathic scoliosis loci on chromosomes 19p13.3, 17p11.2, 9q34, 17q25, and 18q. Conclusions. Our findings confirm that there is a high genetic heterogeneity within the subgroup of dominant forms of idiopathic scoliosis

Two collagen type IX gene polymorphisms that introduce a tryptophan residue into the protein’s triple-helical domain have been linked to an increased risk of lumbar disc disease. To determine whether a particular subset of symptomatic lumbar disease is specifically associated with these polymorphisms, we performed a prospective case-control study of 107 patients who underwent surgery of the lumbar spine. Patients were assigned to one of five clinical categories (fracture, disc degeneration, disc herniation, spinal stenosis without spondylolisthesis and spinal stenosis with spondylolisthesis) based on history, imaging results, and findings during surgery. Of the 11 tryptophan-positive patients, eight had spinal stenosis with spondylolisthesis and three had disc herniation. The presence of the tryptophan allele was significantly associated with African-American or Asian designation for race (odds ratio 4.61, 95% CI 0.63 to 25.35) and with the diagnosis of spinal stenosis with spondylolisthesis (odds ratio 6.81, 95% CI 1.47 to 41.95). Our findings indicate that tryptophan polymorphisms predispose carriers to the development of symptomatic spinal stenosis associated with spondylolisthesis which requires surgery

This study assessed the frequency of acute injury to the spinal cord in Irish Rugby over a period of ten years, between 1995 and 2004. There were 12 such injuries; 11 were cervical and one was thoracic. Ten occurred in adults and two in schoolboys. All were males playing Rugby Union and the mean age at injury was 21.6 years (16 to 36). The most common mechanism of injury was hyperflexion of the cervical spine and the players injured most frequently were playing at full back, hooker or on the wing. Most injuries were sustained during the tackle phase of play. Six players felt their injury was preventable. Eight are permanently disabled as a result of their injury.

Increasing numbers of posterior lumbar fusions are being performed. The purpose of this study was to identify trends in demographics, mortality and major complications in patients undergoing primary posterior lumbar fusion. We accessed data collected for the Nationwide Inpatient Sample for each year between 1998 and 2008 and analysed trends in the number of lumbar fusions, mean patient age, comorbidity burden, length of hospital stay, discharge status, major peri-operative complications and mortality. An estimated 1 288 496 primary posterior lumbar fusion operations were performed between 1998 and 2008 in the United States. The total number of procedures, mean patient age and comorbidity burden increased over time. Hospital length of stay decreased, although the in-hospital mortality (adjusted and unadjusted for changes in length of hospital stay) remained stable. However, a significant increase was observed in peri-operative septic, pulmonary and cardiac complications. Although in-hospital mortality rates did not change over time in the setting of increases in mean patient age and comorbidity burden, some major peri-operative complications increased. These trends highlight the need for appropriate peri-operative services to optimise outcomes in an increasingly morbid and older population of patients undergoing lumbar fusion.