Biomechanical repercussion of sitting posture on lumbar intervertebral discs: A systematic review.

BACKGROUND: The static sitting position contributes to increased pressure on the lumbar intervertebral disc, which can lead to dehydration and decreased disc height. OBJECTIVE: To systematically investigate the of sitting posture on degeneration of the lumbar intervertebral disc. MATERIALS AND METHODS: One researcher carried out a systematic literature search of articles with no language or time limits. Studies from 2006 to 2018 were found. The searches in all databases were carried out on January 28, 2022, using the following databases: Pubmed, Scopus, Embase, Cochrane, and Physiotherapy Evidence Database (PEDro) databases, and for the grey literature: Google scholar, CAPES Thesis and Dissertation Bank, and Open Grey. The acronym PECOS was used to formulate the question focus of this study: P (population) - male and female subjects; E (exposure) - sitting posture; C (comparison) - other posture or sitting posture in different periods; O (outcomes) - height and degeneration of the lumbar intervertebral disc(s), imaging exam; and S (study) - cross-sectional and case control. RESULTS: The risk of bias was in its moderate totality in its outcome: height and degeneration of the lumbar intervertebral disc(s) - imaging. Of the four selected studies, three found a decrease in the height of the disc(s) in sitting posture. CONCLUSION: The individual data from the manuscripts suggest that the sitting posture causes a reduction in the height of the lumbar intervertebral disc. It was also concluded that there is a need for new primary studies with a more in-depth design and sample size.

Immediate effect of upright position on lumbar disc using multiposture MRI: Preliminary results.

Objectives: Gravity loading on lumbar intervertebral discs (IVDs) is affected by body position. Although the long-term effects of gravity on IVDs have been reported, the immediate effects of gravity on IVDs remain unclear. We considered that changes in IVD structure in the upright and supine positions provided new diagnostic information. Therefore, we compared the apparent diffusion coefficient (ADC), transverse relaxation time (T2), and morphology of the lumbar spine between the quickly changing upright and supine positions using an original magnetic resonance imaging (MRI) system that can obtain images in any position (multiposture MRI). Material and Methods: On a 0.4-T multiposture MRI, diffusion-weighted images of the lumbar spine in seven healthy volunteers were obtained using single-shot diffusion echo-planar imaging (b = 0 and 600 s/mm2) in quickly changing upright and supine positions. Moreover, spin-echo images with multiple echo times (echo time = 30, 60, 90, and 120 ms) were obtained in each position. We calculated the ADC and T2 of each IVD (L1 and S1) without any disc degeneration. In addition, the lumbar lordosis angle and length of the lumbar spine were measured to evaluate the morphology of the lumbar spine. Results: The T2 of the IVD between L4 and L5 in the upright position was significantly lower than that in the supine position (P < 0.05). No significant differences were observed in the ADC. The morphology of the lumbar spine did not differ significantly between the two positions. Conclusion: The T2 of the IVD between L4 and L5 was likely decreased by the effect of gravity due to the postural change from supine to upright.

Rotation-traction manipulation induced intradiskal pressure changes in cervical spine-an in vitro study.

Objective: Evaluate the effect of rotation-traction manipulation on intradiskal pressure in human cervical spine specimen with different force and duration parameters, and compare the intradiskal pressure changes between rotation-traction manipulation and traction. Methods: Seven human cervical spine specimens were included in this study. The intradiskal pressure was measured by miniature pressure sensor implanting in the nucleus pulposus. rotation-traction manipulation and cervical spine traction were simulated using the MTS biomechanical machine. Varied thrust forces (50N, 150N, and 250N) and durations (0.05 s, 0.1 s, and 0.15 s) were applied during rotation-traction manipulation with Intradiscal pressure recorded in the neutral position, rotation-anteflexion position, preloading, and thrusting phases. Futuremore, we documented changes in intradiscal pressure during cervical spine traction with different loading forces (50N, 150N, and 250N). And a comparative analysis was performed to discern the impact on intradiscal pressure between manipulation and traction. Results: Manipulation application induced a significant reduction in intradiscal pressure during preloading and thrusting phases for each cervical intervertebral disc (p < 0.05). When adjusting thrust parameters, a discernible decrease in intradiscal pressure was observed with increasing thrust force, and the variations between different thrust forces were statistically significant (p < 0.05). Conversely, changes in duration did not yield a significant impact on intradiscal pressure (p > 0.05). Additionally, after traction with varying loading forces (50N, 150N, 250N), a noteworthy decrease in intradiscal pressure was observed (p < 0.05). And a comparative analysis revealed that rotation-traction manipulation more markedly reduced intradiscal pressure compared to traction alone (p < 0.05). Conclusion: Both rotation-traction manipulation and cervical spine traction can reduce intradiscal pressure, exhibiting a positive correlation with force. Notably, manipulation elicits more pronounced and immediate decompression effect, contributing a potential biomechanical rationale for its therapeutic efficacy.

Posterior Epidural Migration of Lumbar Intervertebral Disc Fragment Mimicking an Epidural Mass.

Acute and chronic lower back pain can be commonly caused by intervertebral disc prolapse. This prolapse usually occurs in the dorsal direction and towards the anterior epidural space. In extremely rare cases, this migration/herniation can be seen approaching the posterior epidural space. One such rare instance has been recorded and described in our patient, a 53-year-old with a history of hypertension who presented with persistent lower back pain, radicular in nature, and recent acute aggravation, leading to mobility impairment. The patient experienced numbness in the lower limbs, urinary incontinence, and irregular bowel movements. Sensory deficits were noted along the L3 dermatome. The patient underwent an L3 laminectomy, revealing extruded disk fragments causing the compression. After surgery, the patient's power in the lower limbs began to improve, with significant recovery by discharge and complete resolution of bowel and bladder incontinence. This case highlights the diagnostic and therapeutic challenges of posterior epidural mass-like lesions in the lumbar spine, emphasizing the importance of prompt surgical intervention in restoring neurological function. The successful outcome underscores the significance of early diagnosis and intervention in such cases, ultimately improving the patient's quality of life.

Histopathology of the Intervertebral Disc of Nothobranchius furzeri, a Fish Model of Accelerated Aging.

INTRODUCTION: Osteoarthritis is a classical age-related disease, which affects millions of patients worldwide. To further understand the pathophysiology and to develop therapeutic strategies for this disease, animal models play a significant role. Nothobranchius furzeri is an established model for accelerated aging that spontaneously develops spinal deformities. Although the bone properties of N. furzeri are well described, characteristics of the intervertebral discs are still unknown. The aim of this study was to investigate the characteristics of the intervertebral discs of healthy and deformed N. furzeri. MATERIAL AND METHODS: Intervertebral properties of healthy and deformed N. furzeri were investigated in 8-, 12-, 18- and 21.5-week-old male fish of the GRZ strain. For histological evaluations the fish were decalcified, paraffin-embedded and stained with (1) hematoxylin and eosin, (2) toluidine blue and (3) alcian blue/picrosirius red. RESULTS: 8-week-old and deformed N. furzeri showed spongy-like tissue containing vacuolated notochord cells and a beginning formation of fibrous tissue in the central area. Older healthy fish showed fibrous tissue in the central region and a spongy-like tissue in the peripheral region. CONCLUSION: Our study revealed age- and disease-related alterations of the vertebral discs in N. furzeri. Further studies should investigate the utility of N. furzeri as a model for degenerative spine diseases.

Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites.

In regenerative medicine, experimental animal models are commonly used to study potential effects of human cells as therapeutic candidates. Although some studies describe certain cells, such as mesenchymal stromal cells (MSC) or human primary cells, as hypoimmunogenic and therefore unable to trigger strong inflammatory host responses, other studies report antibody formation and immune rejection following xenotransplantation. Accordingly, the goal of our study was to test the cellular retention and survival of human-induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) and primary nucleus pulposus cells (NPCs) following their xenotransplantation into immune-privileged knee joints (14 days) and intervertebral discs (IVD; 7 days) of immunocompromised Nude and immunocompetent Sprague Dawley (SD) rats. At the end of both experiments, we could demonstrate that both rat types revealed comparably low levels of systemic IL-6 and IgM inflammation markers, as assessed via ELISA. Furthermore, the number of recovered cells was with no significant difference between both rat types. Conclusively, our results show that xenogeneic injection of human iMSC and NPC into immunoprivileged knee and IVD sites did not lead to an elevated inflammatory response in immunocompetent rats when compared to immunocompromised rats. Hence, immunocompetent rats represent suitable animals for xenotransplantation studies targeting immunoprivileged sites.

Feasibility Study of 3D FACT and IVIM Sequences in the Evaluation of Female Osteoporosis.

BACKGROUND: The aim of this study is to search for the predictive value of 3D fat analysis and calculation technique (FACT) and intravoxel incoherent motion (IVIM) parameters in identifying osteoporosis in women. METHODS: We enrolled 48 female subjects who underwent 3.0 T MRI, including 3D FACT and IVIM sequences. Bone mineral density (BMD) values and Fracture Risk Assessment (FRAX) scores were obtained. Proton density fat fraction (PDFF) in the bone marrow and the real diffusion (D) value of intervertebral discs were measured on 3D FACT and IVIM images, respectively. Accuracy and bias were assessed by linear regression analysis and Bland-Altman plots. Intraclass correlation coefficients were used to assess the measurements' reproducibility. Spearman's rank correlation was applied to explore the correlation. MRI-based parameters were tested for significant differences among the three groups using ANOVA analyses. A receiver operating characteristic (ROC) analysis was performed. RESULTS: The PDFF of the vertebral body showed a negative correlation with BMD (R = -0.393, p = 0.005) and a positive correlation with the FRAX score (R = 0.706, p < 0.001). The D value of intervertebral discs showed a positive correlation with BMD (R = 0.321, p = 0.024) and a negative correlation with the FRAX score (R = -0.334, p = 0.019). The area under the curve values from the ROC analysis showed that the 3D FACT and IVIM sequences could accurately differentiate between normal and osteoporosis (AUC = 0.88 using the PDFF; AUC = 0.77 using the D value). The PDFF value demonstrated a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 78.6%, 89.5%, 84.6%, and 85.0%, respectively, in its ability to predict osteoporosis. The D value had a sensitivity, specificity, PPV, and NPV of 63.16%, 92.9%, 65.0%, and 77.8%, respectively, for predicting osteoporosis. CONCLUSIONS: The 3D FACT- and IVIM-measured PDFF and D values are promising biomarkers in the assessment of bone quality and fracture risk.

Assessment of a Discogenic Pain Animal Model Induced by Applying Continuous Shear Force to Intervertebral Discs.

BACKGROUND: Chronic discogenic pain includes degeneration-driven changes under the mechanical macroenvironment of an internal disc, which leads to the progressive changes of biochemical microenvironment that induce abnormal ingrowth of the nociceptor. The propriety of the animal model reflecting the pathologic natural history has not been assessed. OBJECTIVES: This study investigated the biochemical evidence of chronic discogenic pain by employing a discogenic pain animal model induced by shear force. STUDY DESIGN: Animal study utilizing rats in vivo model of a shear force device. METHODS: Fifteen rats were divided into 3 groups (n = 5/group) according to the period for which sustained dorsoventral shear force was applied (1 week or 2 weeks); the control group received the spinous attachment unit, without a spring. Pain data were collected using von Frey hairs on the hind paws. Growth factor and cytokine abundance was analyzed in the dorsal root ganglion (DRG) and plasma. RESULTS: After the shear force devices were installed, the significant variables were found to markedly increase in the DRG tissues of the 2-week group; however, they were not altered in the 1-week group. Specifically, interleukin (IL)-6, neurogrowth factor (NGF), transforming growth factor (TGF)-alpha, platelet-derived growth factor (PDGF)-beta, and vascular endothelial growth factor (VEGF) were increased. Meanwhile, the plasma levels of tumor necrosis factor-alpha, IL-1beta, IL-5, IL-6, IL-12, and NGF were increased in the 1-week group; whereas, TGF-alpha, PDGF-beta, and VEGF were increased in the 2-week group. LIMITATIONS: The limitations include the general limitations of quadrupedal animals, the poor precision and flexural deformation of shear force devices, inaccuracies regarding the evaluation of histological denaturation, and short intervention and observational periods. CONCLUSIONS: This animal model effectively generated biochemical responses to shear loading with evidence of neurological changes induced without direct macrodamage to the outer annulus fibrosus. Chemical internals were induced by mechanical externals among the contributing factors of chronic discogenic pain.

Extracellular Vesicle-Conjugated Functional Matrix Hydrogels Prevent Senescence by Exosomal miR-3594-5p-Targeted HIPK2/p53 Pathway for Disc Regeneration.

Nucleus pulposus stem cells (NPSCs) senescence plays a critical role in the progression of intervertebral disc degeneration (IDD). Stem cell-derived extracellular vesicles (EV) alleviate cellular senescence. Whereas, the underlying mechanism remains unclear. Low stability largely limited the administration of EV in vivo. RGD, an arginine-glycine-aspartic acid tripeptide, strongly binds integrins expressed on the EV membranes, allowing RGD to anchor EV and prolong their bioavailability. An RGD-complexed nucleus pulposus matrix hydrogel (RGD-DNP) is developed to enhance the therapeutic effects of small EV (sEV). RGD-DNP prolonged sEV retention in vitro and ex vivo. sEV-RGD-DNP promoted NPSCs migration, decreased the number of SA-ß-gal-positive cells, alleviated cell cycle arrest, and reduced p16, p21, and p53 activation. Small RNA-seq showed that miR-3594-5p is enriched in sEV, and targets the homeodomain-interacting protein kinase 2 (HIPK2)/p53 pathway. The HIPK2 knockdown rescues the impaired therapeutic effects of sEV with downregulated miR-3594-5p. RGD-DNP conjugate with lower amounts of sEV achieved similar disc regeneration with free sEV of higher concentrations in DNP. In conclusion, sEV-RGD-DNP increases sEV bioavailability and relieves NPSCs senescence by targeting the HIPK2/p53 pathway, thereby alleviating IDD. This work achieves better regenerative effects with fewer sEV and consolidates the theoretical basis for sEV application for IDD treatment.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Protect Rat Nucleus Pulposus Cells from Oxidative Stress.

BACKGROUND: Oxidative stress (OS) is mainly associated with the pathogenesis of intervertebral disc (IVD) degeneration; it causes nucleus pulposus cells (NPCs) to undergo senescence and triggers autophagy and apoptosis. This study aims to evaluate the regeneration potential of extracellular vesicles (EVs) derived from human umbilical cord-mesenchymal stem cells (hUC-MSCs) in an in vitro rat NPC-induced OS model. DESIGN: NPCs were isolated from rat coccygeal discs, propagated, and characterized. OS was induced by hydrogen peroxide (H2O2), which is confirmed by 2,7-dichlorofluorescein diacetate (H2DCFDA) assay. EVs were isolated from hUC-MSCs and characterized by analyzing the vesicles using fluorescence microscope, scanning electron microscope (SEM), atomic force microscope (AFM), dynamic light scattering (DLS), and Western blot (WB). The in vitro effects of EVs on migration, uptake, and survival of NPCs were determined. RESULTS: SEM and AFM topographic images revealed the size distribution of EVs. The phenotypes of isolated EVs showed that the size of EVs was 403.3 ± 85.94 nm, and the zeta potential was -0.270 ± 4.02 mV. Protein expression analysis showed that EVs were positive for CD81 and annexin V. Treatment of NPCs with EVs reduced H2O2-induced OS as evidenced by a decrease in reactive oxygen species (ROS) levels. Co-culture of NPCs with DiI-labeled EVs showed the cellular internalization of EVs. In the scratch assay, EVs significantly increased NPC proliferation and migration toward the scratched area. Quantitative polymerase chain reaction analysis showed that EVs significantly reduced the expression of OS genes. CONCLUSION: EVs protected NPCs from H2O2-induced OS by reducing intracellular ROS generation and improved NPC proliferation and migration.

A swelling-based biphasic analysis on the quasi-static biomechanical behaviors of healthy and degenerative intervertebral discs.

BACKGROUND AND OBJECTIVE: The degeneration of intervertebral discs is significantly dependent of the changes in tissue composition ratio and tissue structure. Up to the present, the effects of degeneration on the quasi-static biomechanical responses of discs have not been well understood. The goal of this study is to quantitatively analyze the quasi-static responses of healthy and degenerative discs. METHODS: Four biphasic swelling-based finite element models are developed and quantitatively validated. Four quasi-static test protocols, including the free-swelling, slow-ramp, creep and stress-relaxation, are implemented. The double Voigt and double Maxwell models are further used to extract the immediate (or residual), short-term and long-term responses of these tests. RESULTS: Simulation results show that both the swelling-induced pressure in the nucleus pulposus and the initial modulus decrease with degeneration. In the free-swelling test of discs possessing healthy cartilage endplates, simulation results show that over 80% of the total strain is contributed by the short-term response. The long-term response is dominant for discs with degenerated permeability in cartilage endplates. For the creep test, over 50% of the deformation is contributed by the long-term response. In the stress-relaxation test, the long-term stress contribution occupies approximately 31% of total response and is independent of degeneration. Both the residual and short-term responses vary monotonically with degeneration. In addition, both the glycosaminoglycan content and permeability affect the engineering equilibrium time constants of the rheologic models, in which the determining factor is the permeability. CONCLUSIONS: The content of glycosaminoglycan in intervertebral soft tissues and the permeability of cartilage endplates are two critical factors that affect the fluid-dependent viscoelastic responses of intervertebral discs. The component proportions of the fluid-dependent viscoelastic responses depend also strongly on test protocols. In the slow-ramp test, the glycosaminoglycan content is responsible for the changes of the initial modulus. Since existing computational models simulate disc degenerations only by altering disc height, boundary conditions and material stiffness, the current work highlights the significance of biochemical composition and cartilage endplates permeability in the biomechanical behaviors of degenerated discs.

Erratum: A novel approach for tetrahedral-element-based finite element simulations of anisotropic hyperelastic intervertebral disc behavior.

[This corrects the article DOI: 10.3389/fbioe.2022.1034441.].

A novel approach for tetrahedral-element-based finite element simulations of anisotropic hyperelastic intervertebral disc behavior.

Intervertebral discs are microstructurally complex spinal tissues that add greatly to the flexibility and mechanical strength of the human spine. Attempting to provide an adjustable basis for capturing a wide range of mechanical characteristics and to better address known challenges of numerical modeling of the disc, we present a robust finite-element-based model formulation for spinal segments in a hyperelastic framework using tetrahedral elements. We evaluate the model stability and accuracy using numerical simulations, with particular attention to the degenerated intervertebral discs and their likely skewed and narrowed geometry. To this end, 1) annulus fibrosus is modeled as a fiber-reinforced Mooney-Rivlin type solid for numerical analysis. 2) An adaptive state-variable dependent explicit time step is proposed and utilized here as a computationally efficient alternative to theoretical estimates. 3) Tetrahedral-element-based FE models for spinal segments under various loading conditions are evaluated for their use in robust numerical simulations. For flexion, extension, lateral bending, and axial rotation load cases, numerical simulations reveal that a suitable framework based on tetrahedral elements can provide greater stability and flexibility concerning geometrical meshing over commonly employed hexahedral-element-based ones for representation and study of spinal segments in various stages of degeneration.

Effect of intervertebral disc degeneration on the stomatognathic system function in adults.

OBJECTIVE: To analyze the electromyographic activity (EMG) and thermographic patterns of the masseter and temporalis muscles and pressure of the orofacial tissues in individuals with intervertebral disc degeneration (IDD). METHODS: This study had two distinct groups: with IDD (n = 16) and controls (n = 16). EMG at rest, protrusion, right and left laterality, and maximum voluntary contraction were evaluated. Tongue, orbicularis oris, and buccinator muscles pressures were measured by Iowa Oral Performance Instrument. The thermographic patterns were analyzed using infrared thermography. RESULTS: Comparisons between groups showed significant differences regarding at rest [right (p = 0.05) and left (p = 0.05) masseter and right temporal (p = 0.05)], orofacial tissue pressure [tongue (p = 0.001), orbicularis oris (p = 0.01), and buccinator (p = 0.0001)], but no significant differences for the thermographic patterns. CONCLUSION: IDD modifies the functionality of the craniomandibular complex, influencing the performance of the stomatognathic system.

Biomechanical effect of age-related structural changes on cervical intervertebral disc: A finite element study.

Previous literature has investigated the biomechanical response of healthy and degenerative discs, but the biomechanical response of suboptimal healthy intervertebral discs received less attention. The purpose was to compare the biomechanical responses and risk of herniation of young healthy, suboptimal healthy, and degenerative intervertebral discs. A cervical spine model was established and validated using the finite element method. Suboptimal healthy, mildly, moderately, and severely degenerative disc models were developed. Disc height deformation, range of motion, intradiscal pressure, and von Mises stress in annulus fibrosus were analyzed by applying a moment of 4 Nm in flexion, extension, lateral bending, and axial rotation with 100 N compressive loads. Disc height deformation in young healthy, suboptimal healthy, mildly, moderately, and severely degenerative discs was 40%, 37%, 21%, 12%, and 8%, respectively. The decreasing order of the range of motion was young healthy spine > suboptimal healthy spine > mildly degenerative spine > moderately degenerative spine > severely degenerative spine. The mean stress of annulus ground substance in the suboptimal healthy disc was higher than in the young healthy disc. The mean stress of inter-lamellar matrix and annulus ground substance in moderately and severely degenerative discs was higher than in other discs. Age-related structural changes and degenerative changes increased the stiffness and reduced the elastic deformation of intervertebral discs. Decreased range of motion due to the effects of aging or degeneration on the intervertebral disc, may cause compensation of adjacent segments and lead to progressive degeneration of multiple segments. The effect of aging on the intervertebral disc increased the risk of annulus fibrosus damage from the biomechanical point of view. Moderately and severely degenerative discs may have a higher risk of herniation due to the higher risk of damage and layers separation of annulus fibrosus caused by increased stress in the annulus ground substance and inter-lamellar matrix.

A Biodegradable Polymeric Matrix for the Repair of Annulus Fibrosus Defects in Intervertebral Discs.

BACKGROUND: Tissue defects in the annulus fibrosus (AF) due to intervertebral disc (IVD) degeneration or after nucleodiscectomy have little self-healing capacity. To prevent progressive degeneration of the IVD, the AF must be repaired. Biological closure has not yet been achieved and is a challenge for the research community. In this study, a scaffold made of absorbable poly (glycolic acid) (PGA) and hyaluronan (HA) that exhibit excellent biocompatibility and cell colonization properties was used to repair AF defects in an ovine model. METHODS: A partial resection was performed in AF in L3/4 or L4/5 of 10 sheep and PGA-HA scaffolds were implanted on the defects (n = 5), while defects in the control group were left untreated (n = 5). Three months post-operation, the lumbar discs were sectioned and stained with hematoxylin and eosin and safranin-O/fast-green. Histological features including proteoglycan content, annular structure, cellular morphology, blood vessel ingrowth and tear/cleft formation were scored using a modified scoring scheme by 3 investigators and evaluated by a pathologist independently. RESULTS: The treated AF exhibited significantly enhanced repair tissue structure with signs of proteoglycan formation compared to the untreated group. The median scores were 4.3 for the treated and 9.8 for the untreated group. Cystic degeneration, perivascular infiltration, inflammation and necrosis were only present in the untreated group. Blood vessel ingrowth and tear/cleft formation were increased, though not significant, in the untreated group while cell morphology was comparable in both groups. CONCLUSION: PGA-HA scaffolds used for AF closure support repair tissue formation in an ovine lumbar disc defect model.

Multifunctional Nanofibrous Scaffolds with Angle-Ply Microstructure and Co-Delivery Capacity Promote Partial Repair and Total Replacement of Intervertebral Disc.

There is an urgent clinical need for the treatment of annulus fibrosus (AF) impairment caused by intervertebral disc (IVD) degeneration or surgical injury. Although repairing injured AF through tissue engineering is promising, the approach is limited by the complicated angle-ply microstructure, inflammatory microenvironment, poor self-repairing ability of AF cells and deficient matrix production. In this study, electrospinning technology is used to construct aligned core-shell nanofibrous scaffolds loaded with transforming growth factor-ß3 (TGFß3) and ibuprofen (IBU), respectively. The results confirm that the rapid IBU release improves the inflammatory microenvironment, while sustained TGFß3 release enhances nascent extracellular matrix (ECM) formation. Biomaterials for clinical applications must repair local AF defects during herniectomy and enable AF regeneration during disc replacement, so a box defect model and total IVD replacement model in rat tail are constructed. The dual-drug delivering electrospun scaffolds are assembled into angle-ply structure to form a highly biomimetic AF that is implanted into the box defect or used to replace the disc. In two animal models, it is found that biomimetic scaffolds with good anti-inflammatory ability enhance ECM formation and maintain the mechanical properties of IVD. Findings from this study demonstrate that the multifunctional nanofibrous scaffolds provide inspirations for IVD repair.

Recent Advances in Managing Spinal Intervertebral Discs Degeneration.

Low back pain (LBP) represents a frequent and debilitating condition affecting a large part of the global population and posing a worldwide health and economic burden. The major cause of LBP is intervertebral disc degeneration (IDD), a complex disease that can further aggravate and give rise to severe spine problems. As most of the current treatments for IDD either only alleviate the associated symptoms or expose patients to the risk of intraoperative and postoperative complications, there is a pressing need to develop better therapeutic strategies. In this respect, the present paper first describes the pathogenesis and etiology of IDD to set the framework for what has to be combated to restore the normal state of intervertebral discs (IVDs), then further elaborates on the recent advances in managing IDD. Specifically, there are reviewed bioactive compounds and growth factors that have shown promising potential against underlying factors of IDD, cell-based therapies for IVD regeneration, biomimetic artificial IVDs, and several other emerging IDD therapeutic options (e.g., exosomes, RNA approaches, and artificial intelligence).

Different responses of cervical intervertebral disc caused by low and high virulence bacterial infection: a comparative study in rats.

The aims of this study were to investigate the outcomes of low- and high-virulence bacterial cervical intervertebral discs (IVDs) infection and its association with cervical IVDs degeneration in rats. A total of 75 clean grade male rats were used to establish the corresponding animal models of low and high virulent bacterial cervical disc infection via an anterior cervical approach, with injection of Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis (S. epidermidis) with a 29 G needle to cervical IVDs. Specimens were collected for evaluation of Blood routine (Blood-RT), histological staining, and gene expression assays after a magnetic resonance imaging (MRI) scan. There were no statistical differences in all groups in white blood cells (WBC) at 2 and 6 weeks postoperatively (P = 0.136). The highest percentage of neutrophils was found in the S. epidermidis group at 2 weeks postoperatively (P = 0.043). MRI and histology showed that at 6 weeks postoperatively, the puncture group and P. acnes group had similar disc degeneration. In the S. epidermidis group, the disc and subchondral bone structure had been destroyed and bony fusion had occurred after the discitis. The upregulation of pro-inflammatory factor expression had the strongest effect of S. epidermidis on the early stage, while the upregulation in the puncture and P. acnes groups was more persistent. P. acnes infection of the cervical IVDs can lead to degenerative changes, whereas S. epidermidis infection leads to the manifestation of septic discitis. The correlation between P. acnes infection and cervical IVDs degeneration found in clinical studies was confirmed.

Intervertebral Disc Degeneration: Biomaterials and Tissue Engineering Strategies toward Precision Medicine.

Intervertebral disc degeneration is a common cause of discogenic low back pain resulting in significant disability. Current conservative or surgical intervention treatments do not reverse the underlying disc degeneration or regenerate the disc. Biomaterial-based tissue engineering strategies exhibit the potential to regenerate the disc due to their capacity to modulate local tissue responses, maintain the disc phenotype, attain biochemical homeostasis, promote anatomical tissue repair, and provide functional mechanical support. Despite preliminary positive results in preclinical models, these approaches have limited success in clinical trials as they fail to address discogenic pain. This review gives insights into the understanding of intervertebral disc pathology, the emerging concept of precision medicine, and the rationale of personalized biomaterial-based tissue engineering tailored to the severity of the disease targeting early, mild, or severe degeneration, thereby enhancing the efficacy of the treatment for disc regeneration and ultimately to alleviate discogenic pain. Further research is required to assess the relationship between disc degeneration and lower back pain for developing future clinically relevant therapeutic interventions targeted towards the subgroup of degenerative disc disease patients.