Convergence analysis and validation of a discrete element model of the human lumbar spine

Degenerative diseases of the spine can lead to or hasten the onset of additional spinal problems that significantly reduce human mobility. The spine consists of vertebral bodies and intervertebral discs. The most degraded are intervertebral discs. The vertebral body consists of a shell (cortical bone tissue) and an internal content (cancellous bone tissue). The intervertebral disc is a complex structural element of the spine, consisting of the nucleus pulposus, annulus fibrosus, and cartilaginous plates. To develop numerical models for the vertebral body and intervertebral disc, first, it is necessary to verify and validate the models for the constituent elements of the lumbar spine. This paper, for the first time, presents discrete elements-based numerical models for the constituent parts of the lumbar spine, and their verification and validation. The models are validated using uniaxial compression experiments available in the literature. The model predictions are in good qualitative and quantitative agreement with the data of those experiments. The loading rate sensitivity analysis revealed that fluid-saturated porous materials are highly sensitive to loading rate: a 1000-fold increase in rate leads to the increase in effective stiffness of 130 % for the intervertebral disc, and a 250-fold increase in rate leads to the increase in effective stiffness of 50 % for the vertebral body. The developed model components can be used to create an L4-L5 segment model, which, in the future, will allow investigating the mechanical behavior of the spine under different types of loading.

Contrast-enhanced microCT evaluation of degeneration following partial and full width injuries to mouse lumbar intervertebral disc

Study Design: Preclinical animal study. Objective: Evaluation of the degenerative progression resulting from either a partial- or full- width injury to the mouse lumbar intervertebral disc (IVD) using contrast-enhanced micro-computed tomography and histological analyses. We utilized a lateral-retroperitoneal surgical approach to access the lumbar IVD, and the injuries to the IVD were induced by either incising one side of the annulus fibrosus or puncturing both sides of the annulus fibrosus. The full-width injury caused dramatic reduction in nucleus pulposus hydration and significant degeneration. A partial-width injury produces localized deterioration around the annulus fibrosus site that resulted in local tissue remodeling without gross degeneration to the IVD. Methods: Female C57BL/6J mice of 3-4 months age were used in this study. They were divided into three groups to undergo a partial-width, full-width, or sham injuries. The L5/L6 and L6/S1 lumbar IVDs were surgically exposed using a lateral-retroperitoneal approach. The L6/S1 IVDs were injured using either a surgical scalpel (partial-width) or a 33G needle (full-width), with the L5/L6 serving as an internal control. These animals were allowed to recover and then sacrificed at 2-, 4-, or 8- weeks post-surgery. The IVDs were assessed for degeneration using contrast-enhanced microCT (CEμCT) and histological analysis. Results: The high-resolution 3D evaluation of the IVD confirmed that the respective injuries localized within one side of the annulus fibrosus or spanned the full width of the IVD. The full-width injury caused deteriorations in the nucleus pulposus after 2 weeks that culminated in significant degeneration at 8 weeks, while the partial width injury caused localized disruptions that remained limited to the annulus fibrosus. Conclusion: The use of CEμCT revealed distinct IVD degeneration profiles resulting from partial- and full- width injuries. The partial width injury may serve as a better model for IVD degeneration resulting from localized annulus fibrosus injuries in humans.

Three-Dimensional Biomechanical Finite Element Analysis of Lumbar Disc Herniation in Middle Aged and Elderly

Lumbar intervertebral disc protrusion disease refers to the degeneration of intervertebral disc, rupture of fibrous ring, nucleus pulpous protrusion and stimulation or compression of nerve root. The import command in Mimics medical 3D reconstruction software was used to erase the irrelevant image data and obtain vertebral body images. The original 3D model of each vertebral body was built by 3D computing function. A three-dimensional finite element model was established to analyze the effect of different surgical methods on the mechanical distribution of the spine after disentomb. The stress distribution of the spine, intervertebral disc, and left and right articular cartilage at L4/L5 stage and the position shift of the fourth lumbar vertebra were analyzed under 7 working conditions of vertical, forward flexion, extension, left and right flexion, and left and right rotation. The results showed that the established model was effective, and the smaller the area of posterior laminar decompression was, the lesser the impact on spinal stability was. The PELD treatment of lumbar disc herniation had little impact on spinal biomechanics and could achieve good long-term biomechanical stability. Combining the clinical experiment method and finite element simulation, using the advantages of finite element software to optimize the design function can provide guidance for the design and improvement of medical devices and has important significance for the study of clinical mechanical properties and biomechanics.

Mechanism of Action of Mesenchymal Stem Cell-Derived Exosomes in the Intervertebral Disc Degeneration Treatment and Bone Repair and Regeneration

Exosomes are extracellular vesicles formed by various donor cells that regulate gene expression and cellular function in recipient cells. Exosomes derived from mesenchymal stem cells (MSC-Exos) perform the regulatory function of stem cells by transporting proteins, nucleic acids, and lipids. Intervertebral disc degeneration (IDD) is one of the main causes of low back pain, and it is characterized by a decreased number of nucleus pulposus cells, extracellular matrix decomposition, aging of the annulus fibrosus, and cartilage endplate calcification. Besides, nutrient transport and structural repair of intervertebral discs depend on bone and cartilage and are closely related to the state of the bone. Trauma, disease and aging can all cause bone injury. However, there is a lack of effective drugs against IDD and bone injury. Recent MSC-Exos fine tuning has led to significant progress in the IDD treatment and bone repair and regeneration. In this review, we looked at the uniqueness of MSC-Exos, and the potential treatment mechanisms of MSC-Exos with respect to IDD, bone defects and injuries.

Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells

Oxidative stress–induced apoptosis and senescence of nucleus pulposus (NP) cells play a crucial role in the progression of intervertebral disc degeneration (IVDD). Accumulation of studies has shown that activated autophagy and enhanced autophagic flux can alleviate IVDD. In this study, we explored the effects of apigenin on IVDD in vitro and in vivo. Apigenin was found to inhibit tert-butyl hydroperoxide (TBHP)–induced apoptosis, senescence, and ECM degradation in NP cells. In addition, apigenin treatment can restore the autophagic flux blockage caused by TBHP. Mechanistically, we found that TBHP may induce autophagosome and lysosome fusion interruption and lysosomal dysfunction, while apigenin alleviates these phenomena by promoting the nuclear translocation of TFEB via the AMPK/mTOR signaling pathway. Furthermore, apigenin also exerts a protective effect against the progression of IVDD in the puncture-induced rat model. Taken together, these findings indicate that apigenin protects NP cells against TBHP-induced apoptosis, senescence, and ECM degradation via restoration of autophagic flux in vitro, and it also ameliorates IVDD progression in rats in vivo, demonstrating its potential for serving as an effective therapeutic agent for IVDD.

Anti-degenerative effect of melatonin on intervertebral disc: protective contribution against inflammation, oxidative stress, apoptosis, and autophagy

Intervertebral disc (IVD) degeneration is a leading cause of lower back pain. Although the etiology of IVD degeneration (IVDD) is unclear, excessive oxidative stress, inflammation and apoptosis and disruption of autophagy play important role in the pathogenesis of IVDD. Therefore, finding a solution to mitigate these processes could stop or reduce the development of IVDD. Melatonin, a powerful antioxidant, plays an important role in regulating cartilage tissue hemostasis. Melatonin inhibits destruction of extracellular matrix (ECM) of disc. Melatonin preserves ECM contents including sox-9, aggrecan, and collagen II through inhibiting matrix degeneration enzymes such as MMP-13. These protective effects may be mediated by the inhibition of oxidative stress, inflammation and apoptosis, and regulation of autophagy in IVD cells.

Platelet-Derived Growth Factor-BB Inhibits Intervertebral Disc Degeneration via Suppressing Pyroptosis and Activating the MAPK Signaling Pathway

Platelet-derived growth factor-BB (PDGF-BB) is a cytokine involved in tissue repair and tumor progression. It has been found to have expression differences between normal and degenerative intervertebral discs. However, it is not clear whether PDGF-BB has a protective effect on intervertebral disc degeneration (IDD). In this experiment, we treated nucleus pulposus cells (NPCs) with IL-1β to simulate an inflammatory environment and found that the extracellular matrix (ECM) anabolic function of NPCs in an inflammatory state was inhibited. Moreover, the induction of IL-1β also enhanced the expression of NLRP3 and the cleavage of caspase-1 and IL-1β, which activated the pyroptosis of NPCs. In this study, we studied the effect of PDGF-BB on IL-1β-treated NPCs and found that PDGF-BB not only significantly promotes the ECM anabolism of NPCs, but also inhibits the occurrence of pyroptosis and the production of pyroptosis products of NPCs. Consistent with this, when we used imatinib to block the PDGF-BB receptor, the above-mentioned protective effect disappeared. In addition, we found that PDGF-BB can also promote the ECM anabolism of NPCs by regulating the ERK, JNK, PI3K/AKT signaling pathways, but not the P38 signaling pathway. In vivo studies, mice that blocked PDGF-BB receptors showed more severe histological manifestations of intervertebral disc degeneration. In summary, our results indicate that PDGF-BB participates in inhibiting the occurrence and development of IDD by inhibiting pyroptosis and regulating the MAPK signaling pathway.

Computational Modeling Intervertebral Disc Pathophysiology: A Review

Lower back pain is a medical condition of epidemic proportion, and the degeneration of the intervertebral disc has been identified as a major contributor. The etiology of intervertebral disc (IVD) degeneration is multifactorial, depending on age, cell-mediated molecular degradation processes and genetics, which is accelerated by traumatic or gradual mechanical factors. The complexity of such intertwined biochemical and mechanical processes leading to degeneration makes it difficult to quantitatively identify cause–effect relationships through experiments. Computational modeling of the IVD is a powerful investigative tool since it offers the opportunity to vary, observe and isolate the effects of a wide range of phenomena involved in the degenerative process of discs. This review aims at discussing the main findings of finite element models of IVD pathophysiology with a special focus on the different factors contributing to physical changes typical of degenerative phenomena. Models presented are subdivided into those addressing role of nutritional supply, progressive biochemical alterations stemming from an imbalance between anabolic and catabolic processes, aging and those considering mechanical factors as the primary source that induces morphological change within the disc. Limitations of the current models, as well as opportunities for future computational modeling work are also discussed.

Extracellular Vesicles Derived From Stem Cells in Intervertebral Disc Degeneration

Intervertebral disc degeneration (IVDD) is the leading cause of low back pain related to degradation of cartilaginous tissues, mainly resulting from oxidative stress, cell apoptosis, and extracellular matrix degradation. Extracellular vesicles (EVs) exist in all bodily fluids and can be produced by all types of cells. Stem cell-derived EVs (SC-EVs), which are the main paracrine components of stem cells, have gained significant attention in the field of regenerative medicine. Over the past years, accumulating evidence indicates the therapeutic and diagnostic potentials of EVs in IVDD. The main mechanisms involve the induction of regenerative phenotypes, apoptosis alleviation, and immune modulation. In addition, the efficiency of SC-EVs can be enhanced by choosing appropriate donor cells and cell phenotypes, optimizing cell culture conditions, or engineering EVs to deliver drugs and targeting molecules. Given the importance and novelty of SC-EVs, we give an overview of SC-EVs and discuss the roles of SC-EVs in IVDD.