Annulus Fibrosus Research Articles

Omilancor mitigates the senescence of nucleus pulposus cells induced by DDP through targeting MAP2K6.

This study explores the potential of Omilancor in treating Intervertebral Disc Degeneration (IDD) through MAP2K6 targeting. We analyzed mRNA microarray datasets to pinpoint MAP2K6 as a key regulator implicated in IDD progression. Follow-up studies demonstrated that cisplatin (DDP) could prompt cellular senescence in vitro by upregulating MAP2K6 expression. Through molecular docking and other analyses, we identified Omilancor as a compound capable of binding to MAP2K6. This interaction effectively impeded the cellular senescence induced by DDP. We further showed that administration of Omilancor could significantly alleviate the degeneration of IVDs in annulus fibrosus puncture-induced rat model. Omilancor shows promise as a treatment for IDD by targeting MAP2K6-mediated cellular senescence.

Pannexin 3 deletion in mice results in knee osteoarthritis and intervertebral disc degeneration after forced treadmill running.

Pannexin 3 (Panx3) is a glycoprotein that forms mechanosensitive channels expressed in chondrocytes and annulus fibrosus cells of the intervertebral disc (IVD). Evidence suggests Panx3 plays contrasting roles in traumatic versus aging osteoarthritis (OA) and intervertebral disc degeneration (IDD). However, whether its deletion influences the response of joint tissue to forced useis unknown. The purpose of this study was to determine if Panx3 deletion in mice causes increased knee joint OA and IDD after forced treadmill running. Male and female wildtype (WT) and Panx3 knockout (KO) mice were randomized to either a no-exercise group (sedentary; SED) or daily forced treadmill running (forced exercise; FEX) from 24 to 30 weeks of age. Knee cartilage and IVD histopathology were evaluated by histology, while tibial secondary ossification centers were analyzed using microcomputed tomography (µCT). Both male and female Panx3 KO mice developed larger superficial defects of the tibial cartilage after forced treadmill running compared with SED WT mice. Additionally, Panx3 KO mice developed reduced bone volume, and female PANX3 KO mice had lengthening of the lateral tubercle at the intercondylar eminence. In the lower lumbar spine, both male and female Panx3 KO mice developed histopathological features of IDD after running compared to SED WT mice. These findings suggest that the combination of deleting Panx3 and forced treadmill running induces OA and causes histopathological changes associated with the degeneration of the IVDs in mice.

Extracellular Vesicles Functional “Brick‐Cement” Bio‐Integrated System for Annulus Fibrosus Repair

AbstractDue to the deficiency of mechanical supporting after discectomy and weak proliferative capacity of annulus fibrosus (AF) cells, the AF defect repair remains a clinical challenge. Herein, a myofibroblasts derived extracellular vesicles (M‐EVs) functional “brick‐cement” bio‐integrated system (M‐EVs@PGBgel) is developed to repair AF defect. The modified Poly(glycerol‐sebacate) (PGBS), “bio‐brick” layer, exhibited excellent support features on account of its elastomeric mechanical properties. The loaded M‐EVs in the “bio‐cement” layer activated ITGA6/PI3K/AKT pathway, regulated M2 macrophage polarization, thus synergistically promoting AF cell proliferation and migration. The “bio‐cement” layer integrated PGBS and remnant tissue at the defect through the Schiff base reaction and aided M‐EVs’ sustained release. This study demonstrated that M‐EVs@PGBgel significantly improved the disc's biological and mechanical properties in the AF defect microenvironments and promoted AF regeneration in vivo. The M‐EVs@PGBgel shows promise as an effective strategy to simultaneously address the mechanical imbalance and biological disruptions resulting from AF defect.

Pathomechanisms, Pathophysiology and Biomechanics of Degenerative Spine Disease: A Review of Literature

The intervertebral disc in human being is a complex structure and is made up of fibrous and cartilaginous tissues. It is characterized as tension-resisting structure while it allows limited range of motion in axial, bending or rotational posture. Degenerative process of this structure present with clinical morbidity to the patients and possess great challenges to the clinicians while offering care for disc’s pathology. Degeneration begins with imbalance of homeostasis maintained by content of nucleus pulposus and annulus fibrosus. Numerous factors; genetic, mechanical and nutritional, can initiate and or accelerate this degeneration process which ultimately alter the biomechanics of the spine. The aim of this review is to give an overview on the degeneration process, causes and factors influencing disc degeneration, the mechanisms of degeneration and the changes resulted from intervertebral disc degeneration.

Thread-structural microneedles loaded with engineered exosomes for annulus fibrosus repair by regulating mitophagy recovery and extracellular matrix homeostasis

Low back pain is among the most grave public health concerns worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The destruction of annulus fibrosus (AF) is the primary cause of IVDD. A sustainable and stable treatment system for IVDD is lacking because of the special organizational structure and low nutrient supply of AF. We here found that IVDD results in the impaired mitochondrial function of AF tissue, and mitochondrial autophagy (mitophagy) plays a protective role in this process. We therefore reported a thread-structural microneedle (T-MN) matching the ring structure of AF. Based on the adsorption effect of laminin, our T-MN could load with bone marrow mesenchymal stem cell-derived exosomes to envelope the regulating mitophagy microRNA (miRNA 378), named as T-MN@EXO@miR−378. In general, we offered in situ locking in the defect site of AF to prevent nucleus pulposus leakage and promoted AF repair. The design of the thread structure was aimed at bionically matching the layered AF structure, thereby providing stronger adhesion. The T-MN@EXO@miR−378 effectively attached to AF and slowly released therapeutic engineered exosomes, and prevented IVDD progression by restoring mitophagy, promoting AF cell proliferation and migration, and inhibiting the pathological remodeling of the extracellular matrix. This functional system can be used as an excellent tool for sustained drug release and has a certain prospect in substituting the conventional treatment of IVDD.

Comprehensive analysis of gene expression profiles of annulus fibrosus subtypes and hub genes in intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) has been considered a major cause of low back pain. Therefore, further molecular subtypes of IVDD and identification of potential critical genes are urgently needed. First, consensus clustering was used to classify patients with IVDD into two subtypes and key module genes for subtyping were identified using weighted gene co-expression network analysis (WGCNA). Then, key module genes for the disease were identified by WGCNA. Subsequently, SVM and GLM were used to identify hub genes. Based on the above genes, a nomogram was constructed to predict the subtypes of IVDD. Finally, we find that ROM1 is lowered in IVDD and is linked to various cancer prognoses. The present work offers innovative diagnostic and therapeutic biomarkers for molecular subtypes of IVDD.

In Vitro Characterization of Poly(Ethylene Glycol) Dimethacrylate-Nanofibrillated Cellulose as an Injectable Biomaterial for Herniated Nucleus Pulposus Substitute

Highlights:1. Novel synthetic biopolymer hydrogels were successfully prepared from pristine poly(ethylene glycol) dimethacrylate (PEGDMA) and nanofibrillated cellulose (NFC) using the photopolymerization method.2. PEGDMA-NFC biocomposite hydrogel can be developed as an affordable biomaterial for herniated nucleus pulposus substitute, with the potential to meet clinical application standards. Abstract Herniated nucleus pulposus develops when the intervertebral disc portudes through the annulus fibrosus due to the rupture of the annulus fibrosus or a decrease in proteoglycans. Hydrogel implant material can be injected into the disc space to restore disc thickness caused by disc degeneration with minimal invasiveness. This study aimed to characterize poly(ethylene glycol) dimethacrylate-nanofibrillated cellulose (PEGDMA-NFC) in vitro as a potential biomaterial for herniated nucleus pulposus substitute. This study utilized PEGDMA-NFC to treat first-degree herniated nucleus pulposus using the photopolymerization method. PEGDMA was selected because of its hydrophilic ability to produce hydrogel. The addition of NFC to the PEGDMA precursor was expected to show mechanical properties as a hydrogel bio composite candidate. The characterization of PEGDMA-NFC was conducted using three tests: Fourier-transform infrared spectroscopy (FTIR), viscosity assessment, and an in vitro injection testing model. The normal distribution of the data was analyzed using the Kolmogorov-Smirnov test, while the homogeneity was assessed using Levene's test. Homogenous and normally distributed data were analyzed using a one-way analysis of variance (ANOVA) with a p-value of <0.05. The explored concentrations of PEGDMA-NFC included a ratio of 1:0 for the control samples and ratios of 1:0.5 (K1), 1:0.75 (K2), and 1:1 (K3) for the experimental samples. The FTIR analysis revealed the presence of various functional groups in PEGDMA-NFC, indicating its potential classification as a hydrogel biomaterial. The characterization data showed that the K3 sample yielded the most favourable outcome with a viscosity value of 74.67 dPa·s. From the in vitro injection testing result, the addition of NFC demonstrated that the hydrogel would not rupture when released from the mold. The hydrogel could be injected with an 18 gauge needle. The statistical analysis results showed a significant difference among the samples (p<0.05). This study concludes that the PEGDMA-NFC hydrogel biocomposite can be effectively applied in herniated nucleus pulposus cases.

Acute Pain Management in Vatakaphaja Gridhrasi

Gridhrasi is one of the Vataja Nanatmaja Vyadhi in which the vitiated Vata afflicts the Kandara and Sira of lower limb leading to Stambha, Ruk, Toda along with Spandana starting from Kati Pradesha to Prustha, Janu, Jangha and Pada of either one side or both side of the lower limbs. Due to similarities in the clinical presentation, it can be studied under the spectrum of Intervertebral Disc Prolapse of lumbar spine. It is a condition affecting the spine in which the annulus fibrosus is damaged enabling nucleus pulposus to herniate, due to which there will be compression of Spinal Cord or the exiting nerve roots causing severe pain in the low back radiating to lower limbs. The incidence of Herniated disc is about 5 to 20 cases per 1000 adults annually and is most common in male patients when compared with female. In this case a male patient of age 36 suffering with acute pain in the low back region was effectively managed by Nadi Sweda followed by dry cupping for 7 days, followed by Patra Pinda Sweda for 7 days. The study shows significant relief in the pain and remarkable improvement in the range of movement of lumbar spine.

Increased HIF-2α activity in the nucleus pulposus causes intervertebral disc degeneration in the aging mouse spine.

Hypoxia-inducible factors (HIFs) are essential to the homeostasis of hypoxic tissues. Although HIF-2α, is expressed in nucleus pulposus (NP) cells, consequences of elevated HIF-2 activity on disc health remains unknown. We expressed HIF-2α with proline to alanine substitutions (P405A; P531A) in the Oxygen-dependent degradation domain (HIF-2αdPA) in the NP tissue using an inducible, nucleus pulposus-specific K19CreERT allele to study HIF-2α function in the adult intervertebral disc. Expression of HIF-2α in NP impacted disc morphology, as evident from small but significantly higher scores of degeneration in NP of 24-month-old K19CreERT; HIF-2αdPA (K19-dPA) mice. Noteworthy, comparisons of grades within each genotype between 14 months and 24 months indicated that HIF-2α overexpression contributed to more pronounced changes than aging alone. The annulus fibrosus (AF) compartment in the 14-month-old K19-dPA mice exhibited lower collagen turnover and Fourier transform-infrared (FTIR) spectroscopic imaging analyses showed changes in the biochemical composition of the 14- and 24-month-old K19-dPA mice. Moreover, there were changes in aggrecan, chondroitin sulfate, and COMP abundance without alterations in NP phenotypic marker CA3, suggesting the overexpression of HIF-2α had some impact on matrix composition but not the cell phenotype. Mechanistically, the global transcriptomic analysis showed enrichment of differentially expressed genes in themes closely related to NP cell function such as cilia, SLIT/ROBO pathway, and HIF/Hypoxia signaling at both 14- and 24-month. Together, these findings underscore the role of HIF-2α in the pathogenesis of disc degeneration in the aged spine.

Prevertebral Anchored Kevlar Band to Recover Intact Spine Movement Ranges in Lumbar Disc Arthroplasty

Anterior longitudinal ligament and annulus fibrosus removal in total disc replacement induces excessive spinal mobility with zygapophyseal joint overload and osteoarthritic changes causing chronic back pain. To control disc arthroplasty-induced hypermobility with a Kevlar® band. A 3 × 3 cm Kevlar® band implanted in twelve human lumbar cadaveric spines substituted the anterior longitudinal ligament and annulus in disc arthroplasty. Biomechanical studies compared the intact spine, after discectomy, post-disc arthroplasty, and with the Kevlar® band inserted. The Kevlar® band recovered the extension and axial rotation movement ranges without regaining the intact status. Improvement was moderate in lateral bending. The Instantaneous Axis of Rotation improved the discectomy and total disc prosthesis conditions without recovering the initial state. The disc above the operated one also showed increased mobility, particularly in extension and axial rotation, improved by Kevlar® band insertion without recovering the intact spine values. The Kevlar® band improves excess mobility ranges induced by anterior longitudinal ligament and anterior annulus removal in disc arthroplasty in the operated and supra-adjacent discs without recovering the baseline status.

Exploring the Impact of TLR-2 Signaling on miRNA Dysregulation in Intervertebral Disc Degeneration.

Toll-like receptors (TLRs) are key mediators of inflammation in intervertebral disc (IVD) degeneration. TLR-2 activation contributes to the degenerative process by increasing the expression of extracellular matrix-degrading enzymes, pro-inflammatory cytokines, and neurotrophins. As potent post-transcriptional regulators, microRNAs can modulate intracellular mechanisms, and their dysregulation is known to contribute to numerous pathologies. This study aims to investigate the impact of TLR-2 signaling on miRNA dysregulation in the context of IVD degeneration. Small-RNA sequencing of degenerated IVD cells shows the dysregulation of ten miRNAs following TLR-2 activation by PAM2CSK4. The miR-155-5p is most significantly upregulated in degenerated and non-degenerated annulus fibrosus and nucleus pulposus cells. Sequence-based target and pathway prediction shows the involvement of miR-155-5p in inflammation- and cell fate-related pathways and TLR-2-induced miR-155-5p expression leads to the downregulation of its target c-FOS. Furthermore, changes specific to the activation of TLR-2 through fragmented fibronectin are seen in miR-484 and miR-487. Lastly, miR-100-3p, miR-320b, and miR-181a-3p expression exhibit degeneration-dependent changes. These results show that TLR-2 signaling leads to the dysregulation of miRNAs in IVD cells as well as their possible downstream effects on inflammation and degeneration. The identified miRNAs provide important opportunities as potential therapeutic targets for IVD degeneration and low back pain.

Accurate Spatio-Temporal Delivery of Nitric Oxide Facilitates the Programmable Repair of Avascular Dense Connective Tissues Injury.

Avascular dense connective tissues (e.g., the annulus fibrosus (AF) rupture, the meniscus tear, and tendons and ligaments injury) repair remains a challenge due to the "biological barrier" that hinders traditional drug permeation and limits self-healing of the injured tissue. Here, accurate delivery of nitric oxide (NO) to penetrate the "AF biological barrier" is achieved thereby enabling programmable AF repair. NO-loaded BioMOFs are synthesized and mixed in a modified polyvinyl alcohol and PCL-composited electrospun fiber membrane with excellent reactive oxygen species-responsive capability (LN@PM). The results show that LN@PM could respond to the high oxidative stress environment at the injured tissue and realize continuous and substantial NO release. Based on low molecular weight and lipophilicity, NO could penetrate through the "biological barrier" for accurate AF drug delivery. Moreover, the dynamic characteristics of the LN@PM reaction can be matched with the pathological microenvironment to initiate programmable tissue repair including sequential remodeling microenvironment, reprogramming the immune environment, and finally promoting tissue regeneration. This tailored programmable treatment strategy that matches the pathological repair process significantly repairs AF, ultimately alleviating intervertebral disc degeneration. This study highlights a promising approach for avascular dense connective tissue treatment through intelligent NO release, effectively overcoming "AF biological barriers" and programmable treatment.

Shared and Compartment-Specific Processes in Nucleus Pulposus and Annulus Fibrosus During Intervertebral Disc Degeneration.

Elucidating how cell populations promote onset and progression of intervertebral disc degeneration (IDD) has the potential to enable more precise therapeutic targeting of cells and mechanisms. Single-cell RNA-sequencing (scRNA-seq) is performed on surgically separated annulus fibrosus (AF) (19,978; 26,983 cells) and nucleus pulposus (NP) (20,884; 24,489 cells) from healthy and diseased human intervertebral discs (IVD). In both tissue types, depletion of cell subsets involved in maintenance of healthy IVD is observed, specifically the immature cell subsets - fibroblast progenitors and stem cells - indicative of an impairment of normal tissue self-renewal. Tissue-specific changes are also identified. In NP, several fibrotic populations are increased in degenerated IVD, indicating tissue-remodeling. In degenerated AF, a novel disease-associated subset is identified, which expresses disease-promoting genes. It is associated with pathogenic biological processes and the main gene regulatory networks include thrombospondin signaling and FOXO1 transcription factor. In NP and AF cells thrombospondin protein promoted expression of genes associated with TGFβ/fibrosis signaling, angiogenesis, and nervous system development. The data reveal new insights of both shared and tissue-specific changes in specific cell populations in AF and NP during IVD degeneration. These identified mechanisms and molecules are novel and more precise targets for IDD prevention and treatment.

GAS5, a long noncoding RNA, contributes to annulus fibroblast osteogenic differentiation and apoptosis in intervertebral disk degeneration via the miR-221-3p/SOX11 axis.

miR-221-3p has been reported to attenuate the osteogenic differentiation of annulus fibrosus cells (AFs), which has been implicated in intervertebral disk degeneration (IVDD) development. This study aimed to elucidate miR-221-3p's role in osteogenic differentiation and apoptosis of AFs in an IVDD model. After successfully establishing an IVDD rat model by annulus fibrosus needle puncture, AFs were isolated. Bioinformatics, dual-luciferase reporter, and AGO2-RNA immunoprecipitation (RIP) assays predicted and confirmed the potential miR-221-3p lncRNA and gene target. Functional analyses were performed after AF transfection to explore the roles of the identified lncRNA and gene. Western blotting, Alkaline phosphatase (ALP), and Alizarin red and TUNEL staining were performed to investigate AF apoptosis and osteogenic differentiation with different transfections. Compared with AFs isolated from sham rats, IVDD-isolated Afs exhibited stronger osteogenic potential and higher apoptosis rates accompanied by miR-221-3p downregulation. The growth arrest-specific transcript 5 (GAS5) was identified as miR-221-3p's target lncRNA, which was highly expressed in IVDD. GAS5 overexpression facilitated AF apoptosis and osteogenic differentiation, whereas silencing GAS5 had the opposite effect. SRY box-related11 (SOX11) was identified as a downstream miR-221-3p target gene in IVDD. GASS silencing-induced suppression of AF apoptosis and osteogenic differentiation could be reversed by SOX11 overexpression. Our findings uncovered a lncRNA GAS5/miR-221-3p/SOX11 axis in Afs under IVDD, which may help implement novel IVDD therapeutic strategies.

Morphometric variants of remodeling and diastolic function of the left ventricle in late postmenopausal patients with vitamin D deficiency

Aim. To reveal the features of the structural-geometric remodeling of the left chambers of the heart, the diastolic function of the left ventricle and to assess the presence of calcification of the valvular structures of the heart in late postmenopausal women with different levels of vitamin D. Material and methods. The cross-sectional study included 123 postmenopausal women. A standard transthoracic echocardiography was performed with an assessment of morphometric variants of remodeling of the left chambers of the heart and its diastolic function according to the transmitral flow. The significance of differences was assessed using the Mann–Whitney test, χ2 Pearson. Differences and correlations were considered significant at p < 0.05. Results. The median concentration of 25(OH)D in the sample was 20.51 ng/ml (15.8÷26.73). Adequate serum concentration of 25(OH)D was observed in 23 (19%) patients (group 1), in 100 (81%) cases vitamin D deficiency was detected (group 2). In group 1 — 7 (31%) patients had normal geometry (NG) of the left ventricle (LV), LV concentric remodeling (CR) was diagnosed in 1 (4%) case, LV concentric hypertrophy (CH) was diagnosed in 3 (13%) cases, and LV eccentric hypertrophy (EH) was detected in 12 (52%) cases. In Group 2, LV NG was diagnosed in 27 (27%) cases, LV CR was detected in 8 (8%) cases, LV CH was detected in 31 (31%) cases, and LV EH was verified in 34 (34%) cases, the differences are insignificant (p = 0.24). Patients of group 2 showed a statistically significant increase in the volume of the right atrium (RA) and thickness of the posterior wall of the left ventricle (TZSLV). In group 1, in 11 (50%) cases, rigid-type diastolic dysfunction (DD) was detected, and in 11 (50%) cases, a pseudo-normal type of DD was detected. In group 2, pseudonormal myocardial DD was detected in 26 (26%) patients, 74 (74%) patients had rigid-type DD, differences between groups were significant (p < 0.001). Calcifications were found in the annulus fibrosus in 16 (70%) cases in group 1 and in 88 (88%) patients in group 2, the differences were significant (p = 0.04). Conclusion. In the study, data were obtained indicating a significant contribution of vitamin D deficiency to changes in the geometry of the left chambers of the heart, diastolic function of the left ventricle, and calcification of valvular structures.

From hyperglycemia to intervertebral disc damage: exploring diabetic-induced disc degeneration.

The incidence of lumbar disc herniation has gradually increased in recent years, and most patients have symptoms of low back pain and nerve compression, which brings a heavy burden to patients and society alike. Although the causes of disc herniation are complex, intervertebral disc degeneration (IDD) is considered to be the most common factor. The intervertebral disc (IVD) is composed of the upper and lower cartilage endplates, nucleus pulposus, and annulus fibrosus. Aging, abnormal mechanical stress load, and metabolic disorders can exacerbate the progression of IDD. Among them, high glucose and high-fat diets (HFD) can lead to fat accumulation, abnormal glucose metabolism, and inflammation, which are considered important factors affecting the homeostasis of IDD. Diabetes and advanced glycation end products (AGEs) accumulation- can lead to various adverse effects on the IVD, including cell senescence, apoptosis, pyroptosis, proliferation, and Extracellular matrix (ECM) degradation. While current research provides a fundamental basis for the treatment of high glucose-induced IDD patients. further exploration into the mechanisms of abnormal glucose metabolism affecting IDD and in the development of targeted drugs will provide the foundation for the effective treatment of these patients. We aimed to systematically review studies regarding the effects of hyperglycemia on the progress of IDD.

Mechanically tough, adhesive, self-healing hydrogel promotes annulus fibrosus repair via autologous cell recruitment and microenvironment regulation

Annulus fibrosus (AF) defect is an important cause of disc re-herniation after discectomy. The self-regeneration ability of the AF is limited, and AF repair is always hindered by the inflammatory microenvironment after injury. Hydrogels represent one of the most promising materials for AF tissue engineering strategies. However, currently available commercial hydrogels cannot withstand the harsh mechanical load within intervertebral disc. In the present study, an innovative triple cross-linked oxidized hyaluronic acid (OHA)-dopamine (DA)- polyacrylamide (PAM) composite hydrogel, modified with collagen mimetic peptide (CMP) and supplied with transforming growth factor beta 1 (TGF-β1) (OHA-DA-PAM/CMP/TGF-β1 hydrogel) was developed for AF regeneration. The hydrogel exhibited robust mechanical strength, strong bioadhesion, and significant self-healing capabilities. Modified with collagen mimetic peptide, the hydrogel exhibited extracellular-matrix-mimicking properties and sustained the AF cell phenotype. The sustained release of TGF-β1 from the hydrogel was pivotal in recruiting AF cells and promoting extracellular matrix production. Furthermore, the composite hydrogel attenuated LPS-induced inflammatory response and promote ECM synthesis in AF cells via suppressing NFκB/NLRP3 pathway. In vivo, the composite hydrogel successfully sealed AF defects and alleviated intervertebral disk degeneration in a rat tail AF defect model. Histological evaluation showed that the hydrogel integrated well with host tissue and facilitated AF repair. The strategy of recruiting endogenous cells and providing an extracellular-matrix-mimicking and anti-inflammatory microenvironment using the mechanically tough composite OHA-DA-PAM/CMP/TGF-β1 hydrogel may be applicable for AF defect repair in the clinic. Statement of significanceAnnulus fibrosus (AF) repair is challenging due to its limited self-regenerative capacity and post-injury inflammation. In this study, a mechanically tough and highly bioadhesive triple cross-linked composite hydrogel, modified with collagen mimetic peptide (CMP) and supplemented with transforming growth factor beta 1 (TGF-β1), was developed to facilitate AF regeneration. The sustained release of TGF-β1 enhanced AF cell recruitment, while both TGF-β1 and CMP could modulate the microenvironment to promote AF cell proliferation and ECM synthesis. In vivo, this composite hydrogel effectively promoted the AF repair and mitigated the intervertebral disc degeneration. This research indicates the clinical potential of the OHA-DA-PAM/CMP/TGF-β1 composite hydrogel for repairing AF defects.

Return-to-work after interlaminar endoscopic sequestrectomy: case series

BackgroundConsidering the epidemiology of single-level lumbar disc herniations (LDH) in the young and active patients, the impact on working capacity is highly relevant. The timing of return-to-work after lumbar surgery through various modalities differs greatly. This may be partly due diverse disparate surgical approaches along with differences in patient and surgeon. The purpose of this paper is to provide evidence for a return-to-work policy after endoscopic sequestrectomy and discuss possible clues to a faster recovery of patients that did not receive a sick-leave report via a case series.Case presentationThe sample comprises fourteen cases of single-level LDH that underwent endoscopic interlaminar sequestrectomy and did not receive a sick-leave report and were advised to return-to-work whenever they felt fit so. Time until return-to-work, pre- and post-operative leg VAS pain scores and amount of analgesic used post-operatively were retrospectively analyzed. Fourteen patients were operated on using the same technique and on average returned to work after 6.6 ± 1.8 days, used 3.7 ± 2.5 analgesic tablets before returning to work and had a postoperative leg VAS pain score of 1.4 ± 1.2. No patient requested a sick-leave report during the follow-up period of 1 month.ConclusionsThe patients in this case series had a remarkably short period of sick-leave and a low number of analgesic usage. These findings may be due to selection of patients who were operated on specifically for leg pain with the absence of lower back pain suggesting integrity of annulus fibrosus. We can postulate that intraoperative preservation of lamina, facet joint and annulus fibrosus along with reassurance of the surgeon suggesting to return-to-work whenever fell fit so were the key factors in the swifter recovery of the patients.

Strontium ranelate retards disc degradation and improves endplate and bone micro-architecture in ovariectomized rats with lumbar fusion induced – Adjacent segment disc degeneration

ObjectivesAdjacent segment disc degeneration (ASDD) is one of the long-term sequelae of spinal fusion, which is more susceptible with osteoporosis. As an anti-osteoporosis drug, strontium ranelate (SR) has been reported to not only regulate bone metabolism but also cartilage matrix formation. However, it is not yet clear whether SR has a reversal or delaying effect on fusion-induced ASDD in a model of osteoporosis. Materials and methodsFifth three-month-old female Sprague-Dawley rats that underwent L4-L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after bilateral ovariectomy (OVX) surgery. Animals were administered vehicle (V) or SR (900 mg/kg/d) orally for 12 weeks post-PLF as follows: Sham+V, OVX + V, PLF + V, OVX + PLF + V, and OVX + PLF + SR. Manual palpation and X-ray were used to evaluate the state of lumbar fusion. Adjacent-segment disc was assessed by histological (VG staining and Scoring), histomorphometry (Disc Height, MVD, Calcification rate and Vascular Bud rate), immunohistochemical (Col-II, Aggrecan, MMP-13, ADAMTS-4 and Caspase-3), and mRNA analysis (ColI, Col-II, Aggrecan, MMP-13 and ADAMTS-4). Adjacent L6 vertebrae microstructures were evaluated by microcomputed tomography. ResultsManual palpation and radiographs showed clear evidence of the fused segment's immobility. After 12 weeks of PLF surgery, a fusion-induced ASDD model was established. Low bone mass caused by ovariectomy can significantly exacerbate ASDD progression. SR exerted a protective effect on adjacent segment intervertebral disc with the underlying mechanism possibly being associated with preserving bone mass to prevent spinal instability, maintaining the functional integrity of endplate vascular microstructure, and regulating matrix metabolism in the nucleus pulposus and annulus fibrosus. DiscussionAnti-osteoporosis medication SR treatments not only maintain bone mass and prevent fractures, but early intervention could also potentially delay degenerative conditions linked to osteoporosis. Taken together, our results suggested that SR might be a promising approach for the intervention of fusion-induced ASDD with osteoporosis.

Myelo-CT imaging findings in 15 dogs with surgically-treated cervical acute compressive hydrated nucleus pulposus extrusion.

Compressive hydrated nucleus pulposus extrusion (HNPE) is a sudden extrusion of hydrated, nondegenerated nucleus pulposus material with well-known characteristic MRI findings. The appearance of compressive HNPE during contrast-enhanced CT has already been described, but never its myelo-CT characteristics. The aim of this retrospective multicenter case series is to describe the myelo-CT findings in 15 dogs with compressive HNPE confirmed with gross surgical findings. A distinctive and consistent myelo-CT appearance of cervical compressive HNPE in dogs that included a focal extradural "seagull"-shaped extradural compression dorsal to the annulus fibrosus combined with a narrowing of the affected intervertebral disc space was found. The extruded material was hypoattenuating in the soft tissue algorithm. Myelo-CT could be a useful diagnostic tool and influence the clinical decision to address cervical compressive HNPE conservatively or surgically when MRI is not available.