Intact Disc Research Articles

Vascular loops mimicking herniated lumbar discs: fair warning.

The authors report their experience with twenty-one consecutive patients who presented with symptoms and imaging characteristics of a herniated lumbar disc; of whom, at the time of surgery had a vascular loop instead. The procedure was performed on 14 women and seven men with a mean age of 39years. Clinical complaints included lumbar aching with one limb overt radiculopathy in all patients; with additional sphincter dysfunction in two cases. Symptoms had developed within a mean period of three months. In all patients, the disc was exposed through an L5-S1 (n = 10); L4-L5 (n = 5) and L3-L4 (n = 6) open minimal laminotomy. In 16 patients, rather than a herniated disc they had a lumbar epidural varix, while an arterio-venous fistula was found in the remaining five cases. In all cases, the vascular disorder was resected and its subjacent disc was left intact. One patient had a postoperative blood transfusion. While the radiculopathy dysfunction improved in all patients, four patients reported lasting lumbar pain following surgery. The postoperative imaging confirmed the resolution of the vascular anomaly and an intact disc. The mean length of the follow-up period was 47months. Either epidural varix or arterio-venous fistula in the lumbar area may mimic a herniated disc on imaging studies. With the usual technique they can be operated safely. Resection of the anomaly can be sufficient for alleviating radiculopathy symptoms.

Cadaveric biomechanical studies of ADDISC total lumbar disc prosthesis

BackgroundMost total disc replacements provide excessive mobility and not reproduce spinal kinematics, inducing zygapophyseal joint arthritic changes and chronic back pain. In cadaveric lumbosacral spines, we studied if a new lumbar disc prosthesis kinematics mimics the intact intervertebral disc. MethodsIn eight cold preserved cadaveric lumbosacral spines, we registered the movement ranges in flexion, extension, right and left lateral bending, and rotation in the intact status, post-discectomy, and after our prosthesis implantation, comparing them for each specimen. FindingsComparing the intact lumbosacral spine with the L4-L5 prosthesis implanted specimens, we saw statistically significant differences in lateral bending and right rotation but not in the full range of rotation. Analyzing segments, we also noticed statistically significant differences at L4-L5 in flexion-extension and rotation. On the other hand, the L4-L5 discectomy, compared to the baseline spine condition, showed a statistically significant mobility increase in flexion, extension, lateral bending, and axial rotation, with an abnormal instantaneous center of rotation, which destabilizes the segment partly due to anterior annulus surgical removal. Disc prosthesis implantation reversed these changes in instantaneous center of rotation, but the prosthesis failed to restore the initial range of motion due to the destabilization of the ligaments in the operated disc. InterpretationThe ADDISC total disc replacement reproduces the intact disc kinematics and Instantaneous Center of Rotation, but the prosthesis fails to restore the initial range of motion due to ligament destabilization. More studies will be necessary to define a technique that restores the damaged ligaments when implanting the prosthesis.

Study on mechanical properties and failure mode of single-fissure sandstone discs under bi-directional linear loading

The tensile failure of discontinuous geological rock masses in underground spaces is an enduring issue in geotechnical engineering. Understanding the mechanical behaviour and failure characteristics of cracked rock under tension is vital for the safe practice of underground projects. In this study, bi-directional linear load tests were conducted on single-fissure sandstone discs under different stress ratios i (axial stress P1: lateral stress P2) = 1:1, 2:1, 3:1, 4:1, and ∞:1, with crack inclination angles α = 0°, 30°, 45°, 60°, and 90°. The specimens’ deformation characteristics, acoustic emission features, and microfracture characteristics were recorded using the digital image correlation (DIC), PIC-2 acoustic emission(AE) system, and the scanning electron microscopic (SEM). The results showed that the strength at α = 0° was not significantly different from that of intact discs. The AE results and test results indicated that the peak load and initiation load decreased when increasing α and i, and the initiation load approached the peak load. In addition, when the stress ratio was small(i ∼ 1:1), the failure mode of the specimens was mainly controlled by the lateral stress P2. As i increased, the constraint of the lateral stress weakened, and the final failure mode of the specimens was primarily determined by the crack inclination angles. Furthermore, fracture trajectories between adjacent load points were shear cracks, fractures along the axial load line were tensile cracks, and the failure between the end of the fissure and the axial load point was a tensile-shear mixed crack with tensile failure as the dominant mode. DIC displacement vector analysis and SEM results confirmed these failure characteristics. The findings provide a reference for underground support structures' design and safety maintenance.

Anisotropic Fracture of Sandstone with Biotreated Cracks

Biotreatment has the potential to be used in restoration and conservation of stone-cultural relics, but less research has been focused on the anisotropic strength of rock with biotreated cracks. In this study, a series of Brazilian splitting tests (BSTs) was conducted on the intact disc sandstone specimens to generate mimicking natural cracks. A specifically designed biocementing system was then adopted to form effective biocementation between the two halves of the specimen, as indicated by microimages. The sandstone specimens with a biotreated crack were then subjected to BSTs at different loading angles. The apparent tensile strength (ATS) of the biotreated specimen can reach and even exceed that of the intact specimen, with low anisotropy. Furthermore, four failure modes are identified based on optical photos. The aforementioned findings reveal that the biotreatment is a remarkable method for repairing cracks of stone-cultural relics.

Finite element analysis of optimized novel additively manufactured non-articulating prostheses for cervical total disc replacement.

Ball-and-socket designs of cervical total disc replacement (TDR) have been popular in recent years despite the disadvantages of polyethylene wear, heterotrophic ossification, increased facet contact force, and implant subsidence. In this study, a non-articulating, additively manufactured hybrid TDR with an ultra-high molecular weight polyethylene core and polycarbonate urethane (PCU) fiber jacket, was designed to mimic the motion of normal discs. A finite element (FE) study was conducted to optimize the lattice structure and assess the biomechanical performance of this new generation TDR with an intact disc and a commercial ball-and-socket Baguera®C TDR (Spineart SA, Geneva, Switzerland) on an intact C5-6 cervical spinal model. The lattice structure of the PCU fiber was constructed using the Tesseract or the Cross structures from the IntraLattice model in the Rhino software (McNeel North America, Seattle, WA) to create the hybrid I and hybrid II groups, respectively. The circumferential area of the PCU fiber was divided into three regions (anterior, lateral and posterior), and the cellular structures were adjusted. Optimal cellular distributions and structures were A2L5P2 in the hybrid I and A2L7P3 in the hybrid II groups. All but one of the maximum von Mises stresses were within the yield strength of the PCU material. The range of motions, facet joint stress, C6 vertebral superior endplate stress and path of instantaneous center of rotation of the hybrid I and II groups were closer to those of the intact group than those of the Baguera®C group under 100N follower load and pure moment of 1.5 Nm in four different planar motions. Restoration of normal cervical spinal kinematics and prevention of implant subsidence could be observed from the FE analysis results. Superior stress distribution in the PCU fiber and core in the hybrid II group revealed that the Cross lattice structure of a PCU fiber jacket could be a choice for a next-generation TDR. This promising outcome suggests the feasibility of implanting an additively manufactured multi-material artificial disc that allows for better physiological motion than the current ball-and-socket design.

Intradiscal treatment of the cartilage endplate for improving solute transport and disc nutrition.

Poor nutrient transport through the cartilage endplate (CEP) is a key factor in the etiology of intervertebral disc degeneration and may hinder the efficacy of biologic strategies for disc regeneration. Yet, there are currently no treatments for improving nutrient transport through the CEP. In this study we tested whether intradiscal delivery of a matrix-modifying enzyme to the CEP improves solute transport into whole human and bovine discs. Ten human lumbar motion segments harvested from five fresh cadaveric spines (38-66 years old) and nine bovine coccygeal motion segments harvested from three adult steers were treated intradiscally either with collagenase enzyme or control buffer that was loaded in alginate carrier. Motion segments were then incubated for 18h at 37 °C, the bony endplates removed, and the isolated discs were compressed under static (0.2MPa) and cyclic (0.4-0.8 MPa, 0.2Hz) loads while submerged in fluorescein tracer solution (376Da; 0.1mg/ml). Fluorescein concentrations from site-matched nucleus pulposus (NP) samples were compared between discs. CEP samples from each disc were digested and assayed for sulfated glycosaminoglycan (sGAG) and collagen contents. Results showed that enzymatic treatment of the CEP dramatically enhanced small solute transport into the disc. Discs with enzyme-treated CEPs had up to 10.8-fold (human) and 14.0-fold (bovine) higher fluorescein concentration in the NP compared to site-matched locations in discs with buffer-treated CEPs (p < 0.0001). Increases in solute transport were consistent with the effects of enzymatic treatment on CEP composition, which included reductions in sGAG content of 33.5% (human) and 40% (bovine). Whole disc biomechanical behavior-namely, creep strain and disc modulus-was similar between discs with enzyme- and buffer-treated CEPs. Taken together, these findings demonstrate the potential for matrix modification of the CEP to improve the transport of small solutes into whole intact discs.

Nucleus Disc Replacement: Design and Material Selection FEA Analysis

Study Design. We selected the materials and implant design and performed Finite Element Analysis (FEA) studies. Background. Nucleus disc replacements, implanted since 1960, have undergone continuous evolution in materials and designs, but subsidence, extrusion, and in vivo degradation limit widespread use. Aim. The aim of this study is to create a new nucleus disc replacement that avoids the abovementioned drawbacks. Material and Methods. We created eighteen designs with varied materials and analyzed them with FEA in compression and shear tests in a lumbar spine model programmed in Ansys Parametric Design Language. Results. Bionate® 80A had the closest mechanical characteristics to the intact disc nucleus. Monobloc designs bore physiological stresses correctly but suffered significant deformations with permanent damage during surgical insertion through the annulus opening. In addition, sandwich designs were too rigid and had an unreliable curing process. Therefore, we chose an oval doughnut-like 5 mm wall monobloc Bionate® 80A nucleus replacement. It minimized implant stress in loading, distributed loads uniformly, and tolerated lateral compression during implantation. Conclusions. Out of the eighteen designs we analyzed with FEA, we found that the monobloc oval doughnut-like Bionate 80A nucleus replacement reproduced best the biomechanics of the natural disc nucleus and had the lowest subsidence risk as it transmits the load to the ring apophysis. Furthermore, implanting it through the annulotomy required to perform a lumbar microdiscectomy should be possible due to its elasticity. Furthermore, due to its elasticity implanting it through the average annulotomy required to perform a lumbar microdiscectomy should be possible.

Immuno-Modulatory Effects of Intervertebral Disc Cells.

Low back pain is a highly prevalent, chronic, and costly medical condition predominantly triggered by intervertebral disc degeneration (IDD). IDD is often caused by structural and biochemical changes in intervertebral discs (IVD) that prompt a pathologic shift from an anabolic to catabolic state, affecting extracellular matrix (ECM) production, enzyme generation, cytokine and chemokine production, neurotrophic and angiogenic factor production. The IVD is an immune-privileged organ. However, during degeneration immune cells and inflammatory factors can infiltrate through defects in the cartilage endplate and annulus fibrosus fissures, further accelerating the catabolic environment. Remarkably, though, catabolic ECM disruption also occurs in the absence of immune cell infiltration, largely due to native disc cell production of catabolic enzymes and cytokines. An unbalanced metabolism could be induced by many different factors, including a harsh microenvironment, biomechanical cues, genetics, and infection. The complex, multifactorial nature of IDD brings the challenge of identifying key factors which initiate the degenerative cascade, eventually leading to back pain. These factors are often investigated through methods including animal models, 3D cell culture, bioreactors, and computational models. However, the crosstalk between the IVD, immune system, and shifted metabolism is frequently misconstrued, often with the assumption that the presence of cytokines and chemokines is synonymous to inflammation or an immune response, which is not true for the intact disc. Therefore, this review will tackle immunomodulatory and IVD cell roles in IDD, clarifying the differences between cellular involvements and implications for therapeutic development and assessing models used to explore inflammatory or catabolic IVD environments.

Influence of implant parameters on biomechanical stability of TMJ replacement: A finite element analysis.

The articular disc reduces the stress distribution from the mandible to fossa. In total temporomandibular joint (TMJ) replacement, the implant is required to reduce the stress on fossa implant. Current studies lack standard and optimized parameters for the cylindrical dome on Christensen TMJ implant collar. This study briefed a novel TMJ implant head design and investigates the biomechanical behaviour by considering the articular disc. The radius of the head was varied with the height of the cylinder height to obtain the design of the experiment and the stress distribution was compared with an intact mandible-articular disc model by considering the viscoelastic property of the TMJ disc. The model was simulated at three different angles: 20°, 0° and -20° in the mediolateral direction to simulate the manducation. FEA analysis showed high stresses at the circular heads, and high strength is achieved with increased implant cylinder length and diameter. The results also showed a stress reduction of 50% on the fossa from the mandible. Hence, the newly designed head and suggested modifications may be used as a reference for further clinical improvement of Christensen TMJ as well as other TMJ implants.

Pro-inflammatory mediators expression by pulp cells following tooth whitening on restored enamel surface.

This paper aimed to assess the influence of adhesive restoration interface on the diffusion of hydrogen peroxide (H2O2), indirect toxicity, and pro-inflammatory mediators expression by odontoblast-like cells, after in-office tooth whitening. Dental cavities prepared in bovine enamel/dentin discs were adhesively restored and subjected or not to hydrolytic degradation (HD). A whitening gel with 35% H2O2 (WG) was applied for 45 min onto restored and non-restored specimens adapted to artificial pulp chambers giving rise to the groups: SD- intact discs (control); SD/HP- whitened intact discs; RT/HP- restored and whitened discs; and RT/HD/HP- restored and whitened discs subjected to HD. The extracts (culture medium + WG components diffused through enamel/dentin/restoration interface) were collected and applied to odontoblast-like MDPC-23 cells. The study evaluated the amount of H2O2 in the extracts, as well as the cell viability (CV), cell morphology (CM), and gene expression of inflammatory mediators (TNF-α and COX-2) by the pulp cells exposed to the extracts (ANOVA and Tukey tests; 5% significance). All whitened groups presented lower CV than SD (control; p<0.05). The highest CV reduction and gene expression of TNF-α and COX-2 was observed in the RT/HD/HP group in comparison with SD/HP and RT/HP (control; p<0.05). CM alterations occurred in all whitened groups. The intensity of these cell side effects was directly related with the amount of H2O2 in the extracts. We concluded that adhesive restoration of dental cavity increases the H2O2 diffusion after in-office whitening, enhancing the indirect toxicity of this therapy and trigger pro-inflammatory overexpression by MDPC-23 cells.

Disc and Actin Associated Protein 1 influences attachment in the intestinal parasite Giardia lamblia.

The deep-branching eukaryote Giardia lamblia is an extracellular parasite that attaches to the host intestine via a microtubule-based structure called the ventral disc. Control of attachment is mediated in part by the movement of two regions of the ventral disc that either permit or exclude the passage of fluid under the disc. Several known disc-associated proteins (DAPs) contribute to disc structure and function, but no force-generating protein has been identified among them. We recently identified several Giardia actin (GlActin) interacting proteins at the ventral disc, which could potentially employ actin polymerization for force generation and disc conformational changes. One of these proteins, Disc and Actin Associated Protein 1 (DAAP1), is highly enriched at the two regions of the disc previously shown to be important for fluid flow during attachment. In this study, we investigate the role of both GlActin and DAAP1 in ventral disc morphology and function. We confirmed interaction between GlActin and DAAP1 through coimmunoprecipitation, and used immunofluorescence to localize both proteins throughout the cell cycle and during trophozoite attachment. Similar to other DAPs, the association of DAAP1 with the disc is stable, except during cell division when the disc disassembles. Depletion of GlActin by translation-blocking antisense morpholinos resulted in both impaired attachment and defects in the ventral disc, indicating that GlActin contributes to disc-mediated attachment. Depletion of DAAP1 through CRISPR interference resulted in intact discs but impaired attachment, gating, and flow under the disc. As attachment is essential for infection, elucidation of these and other molecular mediators is a promising area for development of new therapeutics against a ubiquitous parasite.

A biomechanical testing method to assess tissue adhesives for annulus closure

Intervertebral disc (IVD) degeneration has been linked to Low Back Pain (LBP) which affects over 80% of the population ranking first in terms of disability worldwide. Degeneration progresses with age and is often accompanied by annulus fibrosus (AF) tearing and nucleus pulposus (NP) herniation. Existing therapies fail to restore IVD function and may worsen AF defects, increasing the risk of reherniation in nearly 30% of patients. Current AF closure options are ineffective, presenting biological or mechanical limitations. Bioadhesives have potential use in this area, however methods to assess performance are limited. Herein, we propose a biomechanical testing method to assess bioadhesives’ capacity to seal AF tears.Two candidate bioadhesives to seal AF tears were evaluated; a tough hydrogel adhesive, and a cyanoacrylate-based glue. The adhesion energy at the interface between bovine discs and the tough hydrogel adhesive was quantified using a peel test (n=4). An experimental method to measure the burst pressure of IVDs was then developed. This method was used to quantify the burst pressure of intact (n=7), injured (AF punctured with a 21G needle; n=7), and sealed IVDs (after applying either the tough hydrogel adhesive patch as a sealant; n=5, or the cyanoacrylate-based glue over the AF tear; n=6).The tough adhesive yielded a strong adhesion energy of 239 ± 49 J/m2 during the peel tests. A maximum pressure of 13.2 ± 3.8 MPa was observed for intact discs in the burst pressure tests, which reduced by 61.4% to 5.1 ± 1.5 MPa in the injured IVDs (p < 0.01)). Application of a cyanoacrylate-based glue to injured IVDs did not recover the burst pressure with statistical significance, however, application of the tough adhesive to injured IVDs, restored burst pressure to 12.3 ± 4.5 MPa, which was not significantly different to the intact burst pressures.In this study, a simple biomechanical method to assess the performance of bioadhesives to seal AF tears based upon burst pressure has been established. Using this method it was found that a tough hydrogel adhesive was able to seal an AF injury, such that the IVD burst pressures were similar to those measured in intact specimens. This method can be used to provide a biomechanical assessment of bioadhesives under high magnitude loading and can complement existing cyclic testing methods that are currently used to assess AF closure devices, improving their assessment before clinical use.

P8. Correlations between sagittal plane disc dimensions and principal surface strains across the L3-4 intact IVD during in vitro multidirectional loading

<h3>BACKGROUND CONTEXT</h3> Understanding the biomechanical behavior of the intact intervertebral disc (IVD) is of great importance when studying disc disease. Experimental data describing the relationship between disc size and sub-regional principal strains of the intact lumbar intervertebral disc during multi-directional loading are lacking. <h3>PURPOSE</h3> The purpose of this study was to investigate possible relationships between lateral view disc dimensions and principal surface strains across different regions of an intact L3-4 disc assessed using digital image correlation (DIC) during multi-directional loading. <h3>STUDY DESIGN/SETTING</h3> Correlation analysis of dimensional data obtained from lateral X-rays of intact L3-4 lumbar discs at rest and principal surface strains of the same discs obtained from digital image correlation analysis during in vitro loading. <h3>PATIENT SAMPLE</h3> There were 14 cadaveric spine segments including 6F/8M, mean(±SD) age: 45±13years; BMD: 0.916±0.120 g/cm2. <h3>OUTCOME MEASURES</h3> Correlation coefficients (and p-values) between disc dimensions (sagittal view disc height and area) and principal surface strains during multi-directional loading, in sub-regions of intact L3-4 IVD. <h3>METHODS</h3> The mean height and depth of the L3-4 IVD of 14 seemingly healthy human spine segments at rest were determined using lateral view X-rays and ImageJ. The IVDs were part of L3-S1 spine segments that were tested using non-destructive loading (7.5 Nm) in flexion (FL), extension (EX), right lateral bending (RLB) right/left axial rotation (RAR/LAR), followed by compression (Comp, 400 N). Mean principal strains (Pmax and Pmin) in four similarly sized quarters of the L3-4 IVD were assessed using 3D DIC (Vic-3D) during loading with cameras positioned directly lateral on the specimen's left side. Relationships between sagittal view disc dimensions at rest and mean principal strains per lateral view disc quarter [Q1(ant)-Q4(post)] during loading were studied using Pearson Correlation analysis (SigmaPlot v14 with p<0.05). <h3>RESULTS</h3> Disc height correlated significantly and positively with Pmax (tensile/stretching strain) mid-anteriorly (Q2) during Comp (R=0.545, p=0.044). There were no other significant correlations between disc height and principal strains in any other region of the disc during any direction of loading (p>0.05). In the mid-posterior disc region (Q3), Pmax correlated significantly and negatively with sagittal plane disc area during FL (R=-0.538, p=0.047) and RLB (R=-0.592, p=0.033, Fig.), showing that a larger disc (taller and deeper) bulges/stretches less during flexion and right lateral bending than a smaller disc (narrow disc height combined with shorter vertebral depth, anterior-posteriorly), mid-posteriorly. Pmin (compressive strain) correlated significantly and positively with sagittal plane disc area in the mid-posterior disc region during Comp (Q3: R=0.650, p=0.012; and Q4: R=0.619, p=0.018), indicating that a larger disc (taller and deeper) shrinks less vertically than a small disc posteriorly during compression. <h3>CONCLUSIONS</h3> Significant relationships were found between disc dimensions and mean principal strains in sagittal view sub-regions of the L3-4 intervertebral disc, during different directions of loading. These relationships aid in understanding intact disc biomechanical behavior during loading and will help improve the quality of finite element models of lumbar spine segments. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Visualizing patterns of intervertebral disc damage with dual-energy computed tomography: assessment of diagnostic accuracy in an ex vivo spine biophantom.

BackgroundPreviously, dual-energy computed tomography (DECT) has been established for imaging spinal fractures as an alternative modality to magnetic resonance imaging (MRI).PurposeTo analyze the diagnostic accuracy of DECT in visualizing intervertebral disc (IVD) damage.Material and MethodsThe lumbar spine of a Great Dane dog was used as an ex vivo biophantom. DECT was performed as sequential volume technique on a single-source CT scanner. IVDs were imaged before and after an injection of sodium chloride solution and after anterior discectomy in single-source sequential volume DECT technique using 80 and 135 kVp. Chondroitin/Collagen maps (cMaps) were reconstructed at 1 mm and compared with standard CT. Standardized regions of interest (ROI) were placed in the anterior anulus fibrosus, nucleus pulposus, and other sites. Three blinded readers classified all images as intact disc, nucleus lesion, or anulus lesion. Additionally, clinical examples from patients with IVD lesions were retrospectively identified from the radiological database.ResultsInterrater reliability was almost perfect with a Fleiss kappa of 0.833 (95% confidence interval [CI] 0.83–0.835) for DECT, compared with 0.780 (95% CI 0.778–0.782) for standard CT. For overall detection accuracy of IVD, DECT achieved 91.0% sensitivity (95% CI 83.6–95.8) and 92.0% specificity (95% CI 80.8–97.8). Standard CT showed 91.0% sensitivity (95% CI 83.6–95.8) and 78.0% specificity (95% CI 64.0–88.5).ConclusionDECT reliably identified IVD damage in an ex vivo biophantom. Clinical examples of patients with different lesions illustrate the accurate depiction of IVD microstructure. These data emphasize the diagnostic potential of DECT cMaps.

The Role of Vertebral Porosity and Implant Loading Mode on Bone-Tissue Stress in the Human Vertebral Body Following Lumbar Total Disc Arthroplasty.

Micro-computed tomography- (micro-CT-) based finite element analysis of cadaveric human lumbar vertebrae virtually implanted with total disc arthroplasty (TDA) implants. (1) Assess the relationship between vertebral porosity and maximum levels of bone-tissue stress following TDA; (2) determine whether the implant's loading mode (axial compression vs. sagittal bending) alters the relationship between vertebral porosity and bone-tissue stress. Implant subsidence may be related to the bone biomechanics in the underlying vertebral body, which are poorly understood. For example, it remains unclear how the stresses that develop in the supporting bone tissue depend on the implant's loading mode or on typical inter-individual variations in vertebral morphology. Data from micro-CT scans from 12 human lumbar vertebrae (8 males, 4 females; 51-89 years of age; bone volume fraction [BV/TV] = 0.060-0.145) were used to construct high-resolution finite element models (37 μm element edge length) comprising disc-vertebra-implant motion segments. Implants were loaded to 800 N of force in axial compression, flexion-, and extension-induced impingement. For comparison, the same net loads were applied via an intact disc without an implant. Linear regression was used to assess the relationship between BV/TV, loading mode, and the specimen-specific change in stress caused by implantation. The increase in maximum bone-tissue stress caused by implantation depended on loading mode (P < 0.001), increasing more in bending-induced impingement than axial compression (for the same applied force). The change in maximum stress was significantly associated with BV/TV (P = 0.002): higher porosity vertebrae experienced a disproportionate increase in stress compared with lower porosity vertebrae. There was a significant interaction between loading mode and BV/TV (P = 0.002), indicating that loading mode altered the relationship between BV/TV and the change in maximum bone-tissue stress. Typically-sized TDA implants disproportionately increase the bone-tissue stress in more porous vertebrae; this affect is accentuated when the implant impinges in sagittal bending.Level of Evidence: N/A.

Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated

We found ADAM8 enzymatic activity elevated in degenerative human intervertebral disc (IVD). Here, we examined the discs in ADAM8-inactivation mice that carry a mutation preventing self-activation of the enzyme. Surprisingly, elevated gene expression for inflammatory markers (Cxcl1, IL6) was observed in injured discs of ADAM8 mutant mice, along with elevated expression of type 2 collagen gene (Col2a1), compared with wild type controls. Injured annulus fibrosus of mutant and wild type mice contained a higher proportion of large collagen fibers compared with intact discs, as documented by microscopic examination under circular polarized light. In the intact IVDs, Adam8EQ mouse AF contained lower proportion of yellow (intermediate) fiber than WT mice. This suggests that ADAM8 may regulate inflammation and collagen fiber assembly. The seemingly contradictory findings of elevated inflammatory markers in mutant mice and excessive ADAM8 activity in human degenerative discs suggest that ADAM8 may interact with other enzymatic and pro-inflammatory processes needed for tissue maintenance and repair. As a future therapeutic intervention to retard intervertebral disc degeneration, partial inhibition of ADAM8 proteolysis may be more desirable than complete inactivation of this enzyme.

AAV6 as an effective gene delivery vector for prolonged transgene expression in intervertebral disc cells in vivo

Intervertebral disc degeneration is the main contributor to low back pain, now the leading cause of disability worldwide. Gene transfer, either in a therapeutic attempt or in basic research to understand the mechanisms of disc degeneration, is a fascinating and promising tool to manipulate the complex physiology of the disc. Viral vectors based on the adeno-associated virus (AAV) have emerged as powerful transgene delivery vehicles yet a systematic investigation into their respective tropism, transduction efficiency, and relative toxicity have not yet been performed in the disc in vivo. Herein, we used in vivo bioluminescence imaging to systematically compare multiple AAV serotypes, injection volumes, titers, promoters, and luciferase reporters to determine which result in high transduction efficiency of murine nucleus pulposus (NP) cells in vivo. We find that AAV6 using a CAG promoter to drive transgene expression, delivered into the NP of murine caudal discs at a titer of 1011 GC/mL, provides excellent transduction efficiency/kinetics and low toxicity in vivo. We also show, for the first time, that the transduction of NP cells can be significantly boosted in vivo by the use of small cell permeabilization peptides. Finally, to our knowledge, we are the first to demonstrate the use of optical tissue clearing and three-dimensional lightsheet microscopy in the disc, which was used to visualize fine details of tissue and cell architecture in whole intact discs following AAV6 delivery. Taken together, these data will contribute to the success of using AAV-mediated gene delivery for basic and translational studies of the IVD.

Transient swelling behavior of the bovine caudal disc

The intervertebral disc is an avascular composite structure, comprised of the nucleus pulposus (NP) and the annulus fibrosus (AF). Previous tissue-level experiments either examined relative differences in swelling capacity of the two disc regions at a single time point or tested explant structures that did not replicate in situ boundary conditions. Previous joint-level studies that investigated time-dependent fluid flow into the disc provided limited information about swelling-induced intradiscal strains with respect to time and boundary constraints. Therefore, the objective of this study was to investigate time-dependent swelling behavior of the intervertebral disc ex situ. The first study investigated time-dependent free-swelling response of the whole disc and the disc's subcomponents separately (i.e., NP and AF). Findings from this study showed that the swelling rate and swelling capacity of NP explants under free-swelling conditions were greater than AF explants. The second study evaluated the effect of boundary conditions on in-plane strain distributions of intact discs and AF rings. Swelling-induced strain was highly heterogeneous in AF rings, where negative circumferential strains were observed in the inner AF and tensile circumferential strains were observed in the outer AF. Radial strains in AF rings were an order of magnitude greater than circumferential strains. Restricting fluid flow only to the outer AF periphery reduced the swelling of the inner AF. Swelling of intact discs affected both NP and AF swelling behaviors, where NP hydration decreased by 60%. Furthermore, the presence of the NP reduced peak radial strains in the AF and resulted in uniform strain distribution throughout the AF. In conclusion, these studies highlight that tissue hydration and swelling-induced strains largely depend on regional biochemical composition and geometric boundary constraints.

Crack initiation and failure of block-in-matrix rocks under Brazilian test using digital image correlation

Bimrocks feature stiff blocks randomly distributed in a soft matrix. Despite their wide distribution in nature, their significant effects on the failure of rock structures such as slopes, mines and tunnels have not been fully understood. Bimrocks behave differently as compared with other rock types since they contain mix of blocks of different strength, size and volume distribution and a matrix of different physical and mechanical characteristics. The purpose of this study is to investigate deformation behaviour and crack development trends of bimrocks containing blocks of different sizes (small <1 mm, medium 2–4 mm, and large 5–8 mm). The Brazilian disc test is performed with the digital image correlation (DIC) technique being employed for deformation analysis. It is found that the size of blocks significantly influences the deformation and failure behaviour of a bimrock. Bimrocks with large blocks exhibit both tensile cracks parallel to the loading direction and shear cracks inclined towards the loading direction. Moreover, the development of plastic deformation is highly dependent upon block size. In particular, bimrocks with large blocks exhibit obvious development of plastic deformation, while no plastic deformation is observed for those with small blocks in the pre-peak loading stage. In fact, the specimens with small blocks cannot be called a bimrock since they behave similar to a homogenous intact disc specimen in which a crack splits the disc into two halves in a typical Brazilian test.

Testing the impact of discoplasty on the biomechanics of the intervertebral disc with simulated degeneration: An in vitro study

Percutaneous Cement Discoplasty has recently been developed to relieve pain in highly degenerated intervertebral discs presenting a vacuum phenomenon in patients that cannot undergo major surgery. Little is currently known about the biomechanical effects of discoplasty. This study aimed at investigating the feasibility of modelling empty discs and subsequent discoplasty surgery and measuring their impact over the specimen geometry and mechanical behaviour. Ten porcine lumbar spine segments were tested in flexion, extension, and lateral bending under 5.4 Nm (with a 200 N compressive force and a 27 mm offset). Tests were performed in three conditions for each specimen: with intact disc, after nucleotomy and after discoplasty. A 3D Digital Image Correlation (DIC) system was used to measure the surface displacements and strains. The posterior disc height, range of motion (ROM), and stiffness were measured at the peak load. CT scans were performed to confirm that the cement distribution was acceptable. Discoplasty recovered the height loss caused by nucleotomy (p = 0.04) with respect to the intact condition, but it did not impact significantly either the ROM or the stiffness. The strains over the disc surface increased after nucleotomy, while discoplasty concentrated the strains on the endplates. In conclusion, this preliminary study has shown that discoplasty recovered the intervertebral posterior height, opening the neuroforamen as clinically observed, but it did not influence the spine mobility or stiffness. This study confirms that this in vitro approach can be used to investigate discoplasty.