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1.
Sci Rep ; 14(1): 13181, 2024 06 08.
Article En | MEDLINE | ID: mdl-38849364

The biomechanical aspects of adjacent segment degeneration after Adult Idiopathic Scoliosis (AdIS) corrective surgery involving postoperative changes in motion and stress of adjacent segments have yet to be investigated. The objective of this study was to evaluate the biomechanical effects of corrective surgery on adjacent segments in adult idiopathic scoliosis by finite element analysis. Based on computed tomography data of the consecutive spine from T1-S1 of a 28-year-old male patient with adult idiopathic scoliosis, a three-dimensional finite element model was established to simulate the biomechanics. Two posterior long-segment fixation and fusion operations were designed: Strategy A, pedicle screws implanted in all segments of both sides, and Strategy B, alternate screws instrumentation on both sides. The range of motion (ROM), Maximum von Mises stress value of intervertebral disc (IVD), and Maximum von Mises stress of the facet joint (FJ) at the fixation adjacent segment were calculated and compared with data of the preoperative AdIS model. Corrective surgery decreased the IVD on the adjacent segments, increased the FJ on the adjacent segments, and decreased the ROM of the adjacent segments. A greater decrease of Maximum von Mises stress was observed on the distal adjacent segment compared with the proximal adjacent segment. The decrease of Maximum von Mises stress and increment of Maximum von Mises stress on adjacent FJ in strategy B was greater than that in strategy A. Under the six operation modes, the change of the Maximum von Mises stress on the adjacent IVD and FJ was significant. The decrease in ROM in the proximal adjacent segment was greater than that of the distal adjacent segment, and the decrease of ROM in strategy A was greater than that in strategy B. This study clarified the biomechanical characteristics of adjacent segments after AdIS corrective surgery, and further biomechanical analysis of two different posterior pedicle screw placement schemes by finite element method. Our study provides a theoretical basis for the pathogenesis, prevention, and treatment of adjacent segment degeneration after corrective surgery for AdIS.


Finite Element Analysis , Range of Motion, Articular , Scoliosis , Spinal Fusion , Humans , Scoliosis/surgery , Scoliosis/physiopathology , Adult , Male , Biomechanical Phenomena , Spinal Fusion/methods , Pedicle Screws , Tomography, X-Ray Computed , Stress, Mechanical , Intervertebral Disc/surgery , Intervertebral Disc/physiopathology , Intervertebral Disc/diagnostic imaging , Thoracic Vertebrae/surgery , Thoracic Vertebrae/physiopathology
2.
Clin Biomech (Bristol, Avon) ; 116: 106270, 2024 Jun.
Article En | MEDLINE | ID: mdl-38776646

BACKGROUND: A novel interspinous fixation system based on anatomical parameters and incorporating transfacetopedicular screws, was developed to treat degenerative disc diseases. The biomechanical characteristics of the novel system were evaluated using finite element analysis in comparison to other classical interspinous spacers. METHODS: The L1-S1 lumbar spine finite element models were surgically implanted with the novel system, Coflex and DIAM devices at the L4/L5 segment to assess the range of motion, the pression distribution of intervertebral disc, the peak stresses on the spinous process and implant during various motions. FINDINGS: Range of motions of the L4/L5 surgical segment were reduced by 29.13%, 61.27%, 77.35%, 33.33%, and the peak stresses of intervertebral disc were decreased by 36.82%, 67.31%, 73.00%, 69.57% for the novel system in flexion, extension, lateral bending, and axial rotation when compared with the Coflex, and they were declined by 34.53%, 57.86%, 75.81%, 25.21%; 36.22%, 67.31%, 75.01%, 71.40% compared with DIAM. The maximum stresses of the spinous process were 29.93 MPa, 24.66 MPa, 14.45 MPa, 24.37 MPa in the novel system, and those of Coflex and DIAM were 165.3 MPa, 109 MPa, 84.79 MPa, 47.66 MPa and 52.59 MPa, 48.78 MPa, 50.27 MPa, 44.16 MPa during the same condition. INTERPRETATION: Compared to other interspinous spacer devices, the novel interspinous fixation system demonstrated excellent stability, effectively distributing load on the intervertebral disc, and reducing the risk of spinous process fractures. The personalized design of the novel interspinous fixation system could be a viable option for treating degenerative disc diseases.


Finite Element Analysis , Intervertebral Disc Degeneration , Lumbar Vertebrae , Range of Motion, Articular , Humans , Intervertebral Disc Degeneration/surgery , Intervertebral Disc Degeneration/physiopathology , Lumbar Vertebrae/surgery , Lumbar Vertebrae/physiopathology , Biomechanical Phenomena , Intervertebral Disc/surgery , Intervertebral Disc/physiopathology , Stress, Mechanical , Bone Screws , Computer Simulation , Male , Spinal Fusion/instrumentation , Spinal Fusion/methods
3.
Clin Biomech (Bristol, Avon) ; 116: 106266, 2024 Jun.
Article En | MEDLINE | ID: mdl-38821035

BACKGROUND: Most ball-in-socket artificial lumbar disc implanted in the spine result in increased hypermobility of the operative level and overloading of the facet joint. METHODS: A finite element model was established and validated for the lumbar spine (L1-L5). The structure of the Mobidisc prosthesis was modified, resulting in the development of two new intervertebral disc prostheses, Movcore and Mcopro. The prostheses were implanted into the L3/L4 level to simulate total disc replacement, and the biomechanical properties of the lumbar spine model were analyzed after the operation. FINDINGS: Following the implantation of the prostheses, the mobility of operative level, peak stress of lumbar spine models, and peak stress of facet joint increased. The performance of mobility was found to be more similar between Movcore and Mobidisc. The mobility and facet joint peak stress of the Mcopro model decreased progressively with an increase in the Young's modulus of the artificial annulus during flexion, extension, and lateral bending. Among all the models, the Mcopro50 model had the mobility closest to the intact model. It showed a 3% decrease in flexion, equal range of motion in extension, a 9% increase in left lateral bending, a 7% increase in right lateral bending, and a 3% decrease in axial rotation. INTERPRETATION: The feasibility of the new intervertebral disc prostheses, Movcore and Mcopro, has been established. The Mcopro prosthesis, which features an artificial annular structure, offers significant advantages in terms of reduced mobility of the operative level and peak stress of facet joint.


Finite Element Analysis , Intervertebral Disc , Lumbar Vertebrae , Range of Motion, Articular , Humans , Lumbar Vertebrae/surgery , Lumbar Vertebrae/physiopathology , Intervertebral Disc/surgery , Intervertebral Disc/physiopathology , Biomechanical Phenomena , Prosthesis Design , Total Disc Replacement/methods , Stress, Mechanical , Prostheses and Implants , Computer Simulation , Models, Biological , Zygapophyseal Joint/surgery , Zygapophyseal Joint/physiopathology
4.
Comput Methods Programs Biomed ; 250: 108172, 2024 Jun.
Article En | MEDLINE | ID: mdl-38669718

BACKGROUND AND OBJECTIVE: Degenerative diseases of the spine have a negative impact on the quality of life of patients. This study presents the results of numerical modelling of the mechanical behaviour of the lumbar spine with patient-specific conditions at physiological loads. This paper aims to numerically study the influence of degenerative changes in the spine and the presence of an endoprosthesis on the creation of conditions for tissue regeneration. METHODS: A numerical model of the mechanical behaviour of lumbar spine at healthy and after total disc replacement under low-energy impacts equivalent to physiological loads is presented. The model is based on the movable cellular automaton method (discrete elements), where the mechanical behaviour of bone tissue is described using the Biot poroelasticity accounting for the presence and transfer of interstitial biological fluid. The nutritional pathways of the intervertebral disc in cases of healthy and osteoporotic bone tissues were predicted based on the analysis of the simulation results according to the mechanobiological principles. RESULTS: Simulation of total disc replacement showed that osseointegration of the artificial disc plates occurs only in healthy bone tissue. With total disc replacement in a patient with osteoporosis, there is an area of increased risk of bone resorption in the near-contact area, approximately 1 mm wide, around the fixators. Dynamic loads may improve the osseointegration of the implant in pathological conditions of the bone tissue. CONCLUSIONS: The results obtained in the case of healthy spine and osteoporotic bone tissues correspond to the experimental data on biomechanics and possible methods of IVD regeneration from the position of mechanobiological principles. The results obtained with an artificial disc (with keel-type fixation) showed that the use of this type of endoprosthesis in healthy bone tissues allows to reproduce the function of the natural intervertebral disc and does not contribute to the development of neoplastic processes. In the case of an artificial disc with osteoporosis of bone tissues, there is a zone with increased risk of tissue resorption and development of neoplastic processes in the area near the contact of the implant attachment. This circumstance can be compensated by increasing the loading level.


Computer Simulation , Intervertebral Disc , Lumbar Vertebrae , Total Disc Replacement , Humans , Lumbar Vertebrae/surgery , Intervertebral Disc/surgery , Intervertebral Disc/physiopathology , Regeneration , Biomechanical Phenomena , Osteoporosis/physiopathology , Osseointegration
5.
DNA Cell Biol ; 41(3): 257-261, 2022 Mar.
Article En | MEDLINE | ID: mdl-35235409

Low back pain (LBP) is a common disorder in orthopedic outpatients, affecting people of all ages, and some patients may develop chronic LBP. As a complex organelle, mitochondria are not only energy workstations but also regulate cell senescence, apoptosis, and homeostasis. Mitochondrial dysfunction promotes disk degeneration by affecting a variety of pathophysiological processes, including oxidative stress, mitophagy, mitochondrial homeostasis, cellular senescence, and cell death. We review the molecular mechanisms underlying the relationship between mitochondrial dysfunction and intervertebral disk degeneration (IDD) to provide a theoretical basis for IDD treatment using pharmacological or tissue-engineering approaches.


Intervertebral Disc Degeneration/physiopathology , Mitochondria/physiology , Animals , Apoptosis/physiology , Cellular Senescence/physiology , Humans , Intervertebral Disc/pathology , Intervertebral Disc/physiopathology , Intervertebral Disc Degeneration/etiology , Intervertebral Disc Degeneration/pathology , Mitochondrial Dynamics/physiology , Models, Biological , Nucleus Pulposus/pathology , Nucleus Pulposus/physiopathology , Oxidative Stress
6.
Orthop Surg ; 14(3): 463-471, 2022 Mar.
Article En | MEDLINE | ID: mdl-35142050

Intervertebral disc degeneration (IDD) disease has been considered as the main cause of low back pain (LBP), which is a very common symptom and the leading cause of disability worldwide today. The pathological mechanism of IDD remains quite complicated, and genetic, developmental, biochemical, and biomechanical factors all contribute to the development of the disease. There exists no effective, non-surgical treatment for IDD nowadays, which is largely related to the lack of knowledge of the specific mechanisms of IDD, and the lack of effective specific targets. Recently, non-coding RNA, including miRNA, has been recognized as an important regulator of gene expression. Current studies on the effects of miRNA in IDD have confirmed that a variety of miRNAs play a crucial role in the process of IDD via nucleus pulposus cells (NPC) apoptosis, abnormal proliferation, inflammatory factors, the extracellular matrix (ECM) degradation, and annulus fibrosus (AF) degeneration. In the past 10 years, research on miRNA has been quite active in IDD. This review summarizes the current research progression of miRNA in the IDD and puts forward some prospects and challenges on non-surgical treatment for IDD.


Intervertebral Disc Degeneration , Intervertebral Disc , Low Back Pain , MicroRNAs , Nucleus Pulposus , Apoptosis , Humans , Intervertebral Disc/physiopathology , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/therapy , MicroRNAs/genetics , Nucleus Pulposus/physiopathology
7.
Medicine (Baltimore) ; 101(1): e27559, 2022 Jan 07.
Article En | MEDLINE | ID: mdl-35029870

ABSTRACT: Most postoperative patients with herniated lumbar disc complained of lower leg radiating pain (LRP), referred buttock pain (RBP), and low back pain (LBP). When discectomy is performed, improvement in LRP is observed due to spinal nerve irritation. However, long-term LBP due to degenerative changes in the disc may occur postoperatively. In addition, limited research has been reported on the short-term (within 1 year) improvement in LBP after discectomy. This study aimed to evaluate the effectiveness of discectomy in reducing LBP within 1 year postoperatively.Among the 183 patients who underwent discectomy performed by a single surgeon from January 2010 to December 2016, 106 who met the inclusion and exclusion criteria were enrolled. In the 106 patients who underwent lumbar discectomy, 3 types of spine-related pain were pre-operatively assessed and 3, 6, and 12 months postoperatively. Functional outcomes were evaluated, and quality of life was assessed 12 months postoperatively by using the Short-Form 36 questionnaire, which was subdivided into mental and physical components.LBP showed both statistical and clinical improvement within the first 3 months postoperatively, but the improvement was not observed until 12 months postoperatively. RBP and LRP showed both statistical and clinical improvement within the first 3 months and further consistently showed statistical improvement. LBP improved clinically only until 3 months postoperatively regardless of the type of herniation.LBP showed improvement within the first 3 months postoperatively and plateaued afterward, and RBP and radiculopathy showed consistent improvement until 12 months postoperatively. This may explain why patients from 12-month follow-up showed improvement in RBP and radiculopathy but not LBP.


Diskectomy/adverse effects , Diskectomy/methods , Intervertebral Disc Displacement/surgery , Intervertebral Disc/surgery , Low Back Pain , Radiculopathy , Adult , Female , Humans , Intervertebral Disc/physiopathology , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/psychology , Low Back Pain/etiology , Low Back Pain/surgery , Lumbar Vertebrae/surgery , Male , Middle Aged , Pain, Postoperative , Quality of Life , Radiculopathy/etiology , Radiculopathy/surgery , Treatment Outcome
8.
Comput Math Methods Med ; 2021: 5824956, 2021.
Article En | MEDLINE | ID: mdl-34790253

INTRODUCTION: Chronic low back pain (LBP) has a wide range of causes. However, most cases are induced by degeneration of the lumbar intervertebral discs (IVDs), and the aching caused by local compression of the affected region has considerable impacts on quality of life. This clinical trial investigated the use of Elgucare, a Chinese herbal formula, as a food supplement to reduce the pain of patients with LBP induced by degeneration of the lumbar IVDs. METHODS: The study assessed patient subjective quality of life, functional limitations caused by LBP, and variations in pain. The assessment was done through the visual analogue scale (VAS) and effects on lumbar IVD thickness, water content, and bone mineral density (BMD). These parameters were evaluated before and after the administration of Elgucare or a placebo, one of which was taken by each participant for a 12-month period. RESULTS: Elgucare reduced the patients' mean VAS pain score by 2.25 points and improved their mean LBP-hampered mobility as assessed by the Roland-Morris Questionnaire by 5.17 points. The results of another questionnaire indicated that Elgucare slowed the LBP-induced deterioration of patients' quality of life, while objective assessment indices obtained through X-ray and magnetic resonance imaging showed that the height and water retention of their IVDs were increased. However, the BMD results showed no improvements. CONCLUSIONS: Elgucare can increase the water retention and height of IVDs and reduce LBP, thereby enhancing quality of life. Therefore, Elgucare can potentially be used as a clinical supplement.


Drugs, Chinese Herbal/therapeutic use , Intervertebral Disc Degeneration/complications , Intervertebral Disc Degeneration/drug therapy , Low Back Pain/drug therapy , Low Back Pain/etiology , Adult , Computational Biology , Female , Humans , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/drug effects , Intervertebral Disc/physiopathology , Intervertebral Disc Degeneration/physiopathology , Low Back Pain/physiopathology , Male , Middle Aged , Pain Measurement , Phytotherapy , Quality of Life , Regeneration/drug effects , Regeneration/physiology , Young Adult
9.
Biomed Pharmacother ; 143: 112170, 2021 Nov.
Article En | MEDLINE | ID: mdl-34536759

Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degenerative disease, which is considered the main cause of low back pain. It seriously affects the quality of life of patients and consequently brings a heavy economic burden to their families and the society. Although IDD is considered a natural process in degenerative lesions, it is mainly caused by aging, trauma, genetic susceptibility and other factors. It is closely related to changes in the tissue structure and function, including the progressive destruction of extracellular matrix, cell aging, cell death of the intervertebral disc (IVD), inflammation, and impairment of tissue biomechanical function. Currently, the treatment of IDD is aimed at alleviating symptoms rather than at targeting pathological changes in the IVD. Furthermore, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway is closely related to various pathological processes in IDD, and the activation of the MAPK/ERK pathway promotes the degradation of the IVD extracellular matrix, cell aging, apoptosis, and inflammatory responses. It also induces autophagy and oxidative stress that accelerate the IVD process. In our current review, we summarize the latest developments in the negative regulation of IDD after activation of the MAPK/ERK signaling pathway and emphasize on its influence on IDD. Targeting this pathway may become an attractive treatment strategy for IDD in the near future.


Anti-Inflammatory Agents/therapeutic use , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Intervertebral Disc Degeneration/drug therapy , Intervertebral Disc/drug effects , Protein Kinase Inhibitors/therapeutic use , Animals , Extracellular Matrix/drug effects , Extracellular Matrix/enzymology , Extracellular Matrix/pathology , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Inflammation Mediators/metabolism , Intervertebral Disc/enzymology , Intervertebral Disc/pathology , Intervertebral Disc/physiopathology , Intervertebral Disc Degeneration/enzymology , Intervertebral Disc Degeneration/pathology , Intervertebral Disc Degeneration/physiopathology , Molecular Targeted Therapy , Signal Transduction
10.
Cells ; 10(9)2021 08 29.
Article En | MEDLINE | ID: mdl-34571890

Intervertebral disc degeneration (IVDD) occurs as a result of an imbalance of the anabolic and catabolic processes in the intervertebral disc, leading to an alteration in the composition of the extracellular matrix (ECM), loss of nucleus pulposus (NP) cells, excessive oxidative stress and inflammation. Degeneration of the IVD occurs naturally with age, but mechanical trauma, lifestyle factors and certain genetic abnormalities can increase the likelihood of symptomatic disease progression. IVDD, often referred to as degenerative disc disease (DDD), poses an increasingly substantial financial burden due to the aging population and increasing incidence of obesity in the United States. Current treatments for IVDD include pharmacological and surgical interventions, but these lack the ability to stop the progression of disease and restore the functionality of the IVD. Biological therapies have been evaluated but show varying degrees of efficacy in reversing disc degeneration long-term. Stem cell-based therapies have shown promising results in the regeneration of the IVD, but face both biological and ethical limitations. Exosomes play an important role in intercellular communication, and stem cell-derived exosomes have been shown to maintain the therapeutic benefit of their origin cells without the associated risks. This review highlights the current state of research on the use of stem-cell derived exosomes in the treatment of IVDD.


Exosomes/transplantation , Intervertebral Disc Degeneration/surgery , Intervertebral Disc/physiopathology , Regeneration , Stem Cell Transplantation , Animals , Exosomes/metabolism , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Humans , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , Intervertebral Disc Degeneration/physiopathology , Recovery of Function
11.
Aging (Albany NY) ; 13(16): 20258-20276, 2021 08 24.
Article En | MEDLINE | ID: mdl-34428744

Intervertebral disc degeneration (IVDD) is a main cause of low back pain that is associated with extracellular matrix (ECM) degradation and inflammation. This study aims to investigate the role of DNMT3B and its regulatory mechanisms in IVDD. IVDD rat models were constructed followed by transfections with oe-DNMT3B or oe-YAP in order to explore the role of DNMT3B in the development of IVDD. After that transfection, nucleus pulposus (NP) cells were isolated and transfected with oe-DNMT3B, oe-TRPA1, si-YAP, oe-YAP or oe-COX2 in order to investigate the functions of DNMT3B in NP cells. DNMT3B was poorly expressed in IVDD tissues and NP cells whereas TRPA1, COX2, and YAP were highly expressed. The proliferation or apoptosis of NP cells was detected through CCK-8 assay or flow cytometry, respectively. Overexpression of DNMT3B promoted the proliferation of NP cells, inhibited their apoptosis, as well as increasing the expression of collagen II and aggrecan and decreasing expression of MMP3 and MMP9. Besides, DNMT3B suppressed inflammation and alleviated IVDD. Mechanistically, DNMT3B modified the TRPA1 promoter by methylation to inhibit the expression of COX2. Overexpression of COX2 promoted the apoptosis of NP cells and decreased the expression of YAP, which was reversed by upregulating DNMT3B. DNMT3B may promote the proliferation of NP cells and prevent their ECM degradation through the TRPA1/COX2/YAP axis, thereby alleviating IVDD in rats.


Cyclooxygenase 2/metabolism , DNA (Cytosine-5-)-Methyltransferases/metabolism , Extracellular Matrix/metabolism , TRPA1 Cation Channel/metabolism , YAP-Signaling Proteins/metabolism , Animals , Cyclooxygenase 2/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , Extracellular Matrix/enzymology , Extracellular Matrix/genetics , Humans , Intervertebral Disc/metabolism , Intervertebral Disc/physiopathology , Intervertebral Disc Degeneration/metabolism , Male , Methylation , Rats , Rats, Sprague-Dawley , TRPA1 Cation Channel/genetics , YAP-Signaling Proteins/genetics , DNA Methyltransferase 3B
12.
J Orthop Surg Res ; 16(1): 391, 2021 Jun 17.
Article En | MEDLINE | ID: mdl-34140040

BACKGROUND: The superior facet arthroplasty is important for intervertebral foramen microscopy. To our knowledge, there is no study about the postoperative biomechanics of adjacent L4/L5 segments after different methods of S1 superior facet arthroplasty. To evaluate the effect of S1 superior facet arthroplasty on lumbar range of motion and disc stress of adjacent segment (L4/L5) under the intervertebral foraminoplasty. METHODS: Eight finite element models (FEMs) of lumbosacral vertebrae (L4/S) had been established and validated. The S1 superior facet arthroplasty was simulated with different methods. Then, the models were imported into Nastran software after optimization; 500 N preload was imposed on the L4 superior endplate, and 10 N⋅m was given to simulate flexion, extension, lateral flexion and rotation. The range of motion (ROM) and intervertebral disc stress of the L4-L5 spine were recorded. RESULTS: The ROM and disc stress of L4/L5 increased with the increasing of the proportions of S1 superior facet arthroplasty. Compared with the normal model, the ROM of L4/L5 significantly increased in most directions of motion when S1 superior facet formed greater than 3/5 from the ventral to the dorsal or 2/5 from the apex to the base. The disc stress of L4/L5 significantly increased in most directions of motion when S1 superior facet formed greater than 3/5 from the ventral to the dorsal or 1/5 from the apex to the base. CONCLUSION: In this study, the ROM and disc stress of L4/L5 were affected by the unilateral S1 superior facet arthroplasty. It is suggested that the forming range from the ventral to the dorsal should be less than 3/5 of the S1 upper facet joint. It is not recommended to form from apex to base. LEVEL OF EVIDENCE: Level IV.


Arthroplasty/methods , Biomechanical Phenomena , Finite Element Analysis , Lumbar Vertebrae/surgery , Humans , Intervertebral Disc/physiopathology , Lumbar Vertebrae/physiopathology , Male , Postoperative Period , Range of Motion, Articular
13.
Int J Mol Sci ; 22(7)2021 Mar 29.
Article En | MEDLINE | ID: mdl-33805356

Chronic low back pain (LBP) remains a challenging condition to treat, and especially to cure. If conservative treatment approaches fail, the current "gold standard" for intervertebral disc degeneration (IDD)-provoked back pain is spinal fusion. However, due to its invasive and destructive nature, the focus of orthopedic research related to the intervertebral disc (IVD) has shifted more towards cell-based therapeutic approaches. They aim to reduce or even reverse the degenerative cascade by mimicking the human body's physiological healing system. The implementation of progenitor and/or stem cells and, in particular, the delivery of mesenchymal stromal cells (MSCs) has revealed significant potential to cure the degenerated/injured IVD. Over the past decade, many research groups have invested efforts to find ways to utilize these cells as efficiently and sustainably as possible. This narrative literature review presents a summary of achievements made with the application of MSCs for the regeneration of the IVD in recent years, including their preclinical and clinical applications. Moreover, this review presents state-of-the-art strategies on how the homing capabilities of MSCs can be utilized to repair damaged or degenerated IVDs, as well as their current limitations and future perspectives.


Intervertebral Disc Degeneration/therapy , Intervertebral Disc/physiopathology , Mesenchymal Stem Cell Transplantation , Regeneration , Animals , Humans , Intervertebral Disc/injuries , Intervertebral Disc Degeneration/physiopathology
14.
Biomed Res Int ; 2021: 5563296, 2021.
Article En | MEDLINE | ID: mdl-33860035

Cervical spondylotic radiculopathy (CSR) is the most commonly encountered cervical spine disorder. Cervical manipulation has been demonstrated as an effective therapy for patients. However, the mechanisms of manipulations have not been elucidated. A total of 120 cervical spondylotic radiculopathy patients were divided into the "three-dimensional balanced manipulation" treatment group (TBM group) and control group randomly. The control group was treated with traditional massage; the TBM treatment group was treated with "three-dimensional balanced manipulation" based on traditional massage. The symptoms and clinical efficacy of the patients were compared before and after treatment for one month. A three-dimensional finite element model was established. The mechanical parameters were imported to simulate TBM, and finite element analysis was performed. The results showed that the total effective rate was significantly higher in the TBM group compared with the control group. The biomechanical analysis showed the vertebral body stress was mainly distributed in the C3/4 spinous processes; the deformation mainly concentrated in the anterior processes of the C3 vertebral body. The intervertebral disc stress in the C3~C7 segment was mainly distributed in the anterior part of the C3/4 intervertebral disc, and the deformation extends to the posterior part of the C3/4 nucleus pulposus. In summary, these data are suggesting that TBM was effective in CSR treatment. The results of the finite element model and biomechanical analysis provide an important foundation for effectively avoiding iatrogenic injuries and improving the effect of TBM in the treatment of CSR patients.


Finite Element Analysis , Manipulation, Spinal/adverse effects , Radiculopathy/complications , Radiculopathy/physiopathology , Spondylosis/complications , Spondylosis/physiopathology , Biomechanical Phenomena , Cervical Vertebrae/pathology , Cervical Vertebrae/physiopathology , Humans , Intervertebral Disc/pathology , Intervertebral Disc/physiopathology , Treatment Outcome , Vertebral Body/pathology , Vertebral Body/physiopathology
15.
Nat Rev Rheumatol ; 17(3): 158-175, 2021 03.
Article En | MEDLINE | ID: mdl-33526926

Intervertebral disc (IVD) degeneration is a major cause of low back pain, a prevalent and chronic condition that has a striking effect on quality of life. Currently, no approved pharmacological interventions or therapies are available that prevent the progressive destruction of the IVD; however, regenerative strategies are emerging that aim to modify the disease. Progress has been made in defining promising new treatments for disc disease, but considerable challenges remain along the entire translational spectrum, from understanding disease mechanism to useful interpretation of clinical trials, which make it difficult to achieve a unified understanding. These challenges include: an incomplete appreciation of the mechanisms of disc degeneration; a lack of standardized approaches in preclinical testing; in the context of cell therapy, a distinct lack of cohesion regarding the cell types being tested, the tissue source, expansion conditions and dose; the absence of guidelines regarding disease classification and patient stratification for clinical trial inclusion; and an incomplete understanding of the mechanisms underpinning therapeutic responses to cell delivery. This Review discusses current approaches to disc regeneration, with a particular focus on cell-based therapeutic strategies, including ongoing challenges, and attempts to provide a framework to interpret current data and guide future investigational studies.


Cell- and Tissue-Based Therapy/methods , Intervertebral Disc Degeneration/therapy , Humans , Intervertebral Disc/physiology , Intervertebral Disc/physiopathology , Intervertebral Disc Degeneration/complications , Intervertebral Disc Degeneration/physiopathology , Low Back Pain/etiology , Regeneration
16.
J Orthop Surg Res ; 16(1): 88, 2021 Jan 28.
Article En | MEDLINE | ID: mdl-33509235

BACKGROUND: Regarding the repair of vertebral compression fractures, there is a lack of adequate biomechanical verification as to whether only half of the vertebral body and the upper and lower intervertebral discs affect spinal biomechanics; there also remains debate as to the appropriate length of fixation. METHODS: A model of old vertebral compression fractures with kyphosis was established based on CT data. Vertebral column resection (VCR) and posterior unilateral vertebral resection and reconstruction (PUVCR) were performed at T12; long- and short-segment fixation methods were applied, and we analyzed biomechanical changes after surgery. RESULTS: Range of motion (ROM) decreased in all fixed models, with lumbar VCR decreasing the most and short posterior unilateral vertebral resection and reconstruction (SPUVCR) decreasing the least; in the long posterior unilateral vertebral resection and reconstruction (LPUVCR) model, the internal fixation system produced the maximum VMS stress of 213.25 mPa in a lateral bending motion and minimum stress of 40.22 mPa in a lateral bending motion in the SVCR. CONCLUSION: There was little difference in thoracolumbar ROM between PUVCR and VCR models, while thoracolumbar ROM was smaller in long-segment fixation than in short-segment fixation. In all models, the VMS was most significant at the screw-rod junction and greatest at the ribcage-vertebral body interface, partly explaining the high probability of internal fixation failure and prosthesis migration in these two positions.


Finite Element Analysis , Fracture Fixation, Internal/methods , Fractures, Compression/surgery , Intervertebral Disc/surgery , Lumbar Vertebrae/surgery , Osteotomy/methods , Plastic Surgery Procedures/methods , Spinal Fractures/surgery , Thoracic Vertebrae/surgery , Adult , Biomechanical Phenomena , Fractures, Compression/physiopathology , Humans , Intervertebral Disc/physiopathology , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/physiopathology , Male , Range of Motion, Articular , Spinal Fractures/diagnostic imaging , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/physiopathology , Tomography, X-Ray Computed
17.
Int J Mol Sci ; 22(2)2021 Jan 12.
Article En | MEDLINE | ID: mdl-33445782

Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations' processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.


Intervertebral Disc Degeneration/physiopathology , Intervertebral Disc/physiopathology , Animals , Computer Simulation , Extracellular Matrix/physiology , Humans , Signal Transduction/physiology , Tissue Engineering/methods
18.
J Biomater Appl ; 35(10): 1327-1336, 2021 05.
Article En | MEDLINE | ID: mdl-33349103

BACKGROUND: Laminectomy is a traditional method for treating lumbar diseases; however, the destruction of the posterior structures may cause postoperative symptoms. An individualized poly-ether-ether-ketone (PEEK) artificial lamina was designed to reconstruct the posterior structures after laminectomy. This study aimed to explore the biomechanical effects of reconstruction of the posterior structures with an individualized PEEK artificial lamina using validated finite element models. OBJECTIVE: To examine the biomechanical effects of individualized PEEK artificial lamina on postlaminectomy lumbar. METHODS: A finite element (FE) model of L3-5 was developed based on computed tomography images. Four surgical models (laminectomy, artificial lamina alone, ligament reconstruction, and osseointegration) were constructed, representing different stages of L4 artificial lamina implantation. The range of motion (ROM), intradiscal pressure (IDP), stresses in the annulus fibrosus at the surgical level and cephalad adjacent level, and stresses in the artificial lamina and screws were measured. RESULTS: The ROM, IDP, and stresses in the annulus fibrosus of the different artificial lamina models decreased compared to those of the laminectomy model at both surgical and adjacent levels for all motion patterns, most notably in the osseointegration model. In addition, the results of the stresses in the implants showed that the artificial lamina could enhance the lumbar isthmus and disperse the abnormally concentrated stresses after laminectomy. CONCLUSION: The application of a PEEK artificial lamina has the potential to stabilize the postlaminectomy lumbar spine and prevent adjacent segment disease (ASD) and iatrogenic lumbar deformities, resulting in a reduction in the incidence of post-lumbar surgery syndrome.


Benzophenones/chemistry , Intervertebral Disc Degeneration/surgery , Intervertebral Disc Displacement/surgery , Polymers/chemistry , Prostheses and Implants , Adult , Annulus Fibrosus/physiopathology , Finite Element Analysis , Humans , Intervertebral Disc/physiopathology , Laminectomy , Male , Models, Anatomic , Pedicle Screws , Pressure , Range of Motion, Articular , Stress, Physiological
19.
Ann Biomed Eng ; 49(2): 601-616, 2021 Feb.
Article En | MEDLINE | ID: mdl-32785861

The development of adjacent segment degeneration (ASD) is a major concern after lumbar spinal fusion surgery, but the causative mechanisms remain unclear. This study used a combined in vivo and in silico method to investigate the changes of anatomical dimensions and biomechanical responses of the adjacent segment (L3-4) after spinal fusion (L4-S1) in five patients under weight-bearing upright standing conditions. The in vivo adjacent disc height changes before and after fusion were measured using a dual fluoroscopic imaging system (DFIS), and the measured in vivo intervertebral positions and orientations were used as displacement boundary conditions of the patient-specific three-dimensional (3D) finite element (FE) disc models to simulate the biomechanical responses of adjacent discs to fusion of the diseased segments. Our data (represented by medians and 95% confidence intervals) showed that a significant decrease by - 0.8 (- 1.2, - 0.4) mm (p < 0.05) in the adjacent disc heights occurred at the posterior region after fusion. The significant increases in disc tissue strains and stresses, 0.32 (0.21, 0.43) mm/mm (p < 0.05) and 1.70 (1.07, 3.60) MPa (p < 0.05), respectively, after fusion were found in the posterolateral portions of the outermost annular lamella. The intradiscal pressure of the adjacent disc was significantly increased by 0.29 (0.13, 0.47) MPa after fusion (p < 0.05). This study demonstrated that fusion could cause alterations in adjacent disc biomechanics, and the combined in vivo and in silico method could be a valuable tool for the quantitative assessment of ASD after fusion.


Intervertebral Disc Degeneration/physiopathology , Intervertebral Disc/physiopathology , Low Back Pain/physiopathology , Lumbar Vertebrae/physiopathology , Spinal Fusion , Aged , Biomechanical Phenomena , Computer Simulation , Female , Finite Element Analysis , Humans , Intervertebral Disc/surgery , Intervertebral Disc Degeneration/surgery , Low Back Pain/surgery , Lumbar Vertebrae/surgery , Male , Middle Aged
20.
Biomech Model Mechanobiol ; 20(1): 281-291, 2021 Feb.
Article En | MEDLINE | ID: mdl-32949306

The nucleus pulposus (NP) in the intervertebral disk (IVD) depends on diffusive fluid transport for nutrients through the cartilage endplate (CEP). Disruption in fluid exchange of the NP is considered a cause of IVD degeneration. Furthermore, CEP calcification and sclerosis are hypothesized to restrict fluid flow between the NP and CEP by decreasing permeability and porosity of the CEP matrix. We performed a finite element analysis of an L3-L4 lumbar functional spine unit with poro-elastic constitutive equations. The aim of the study was to predict changes in the solid and fluid parameters of the IVD and CEP under structural changes in CEP. A compressive load of 500 N was applied followed by a 10 Nm moment in extension, flexion, lateral bending, and axial rotation to the L3-L4 model with fully saturated IVD, CEP, and cancellous bone. A healthy case of L3-L4 physiology was then compared to two cases of CEP sclerosis: a calcified cartilage endplate and a fluid constricted sclerotic cartilage endplate. Predicted NP fluid velocity increased for the calcified CEP and decreased for the calcified + less permeable CEP. Decreased NP fluid velocity was prominent in the axial direction through the CEP due to a less permeable path available for fluid flux. Fluid pressure and maximum principal stress in the NP were predicted to increase in both cases of CEP sclerosis compared to the healthy case. The porous medium predictions of this analysis agree with the hypothesis that CEP sclerosis decreases fluid flow out of the NP, builds up fluid pressure in the NP, and increases the stress concentrations in the NP solid matrix.


Cartilage/physiopathology , Elasticity , Finite Element Analysis , Nucleus Pulposus/physiopathology , Rheology , Sclerosis/physiopathology , Cartilage/diagnostic imaging , Humans , Imaging, Three-Dimensional , Intervertebral Disc/physiopathology , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/physiopathology , Male , Middle Aged , Nucleus Pulposus/diagnostic imaging , Permeability , Porosity , Pressure , Reproducibility of Results , Sclerosis/diagnostic imaging , Stress, Mechanical , Tomography, X-Ray Computed
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