Biomechanical Analysis of Hybrid Artificial Discs or Zero-Profile Devices for Treating 1-Level Adjacent Segment Degeneration in ACDF Revision Surgery.

OBJECTIVE: Cervical hybrid surgery optimizes the use of cervical disc arthroplasty (CDA) and zero-profile (ZOP) devices in anterior cervical discectomy and fusion (ACDF) but lacks uniform combination and biomechanical standards, especially in revision surgery (RS). This study aimed to investigate the biomechanical characteristics of adjacent segments of the different hybrid RS constructs in ACDF RS. METHODS: An intact 3-dimensional finite element model generated a normal cervical spine (C2-T1). This model was modified to the primary C5-6 ACDF model. Three RS models were created to treat C4-5 adjacent segment degeneration through implanting cages plus plates (Cage-Cage), ZOP devices (ZOP-Cage), or Bryan discs (CDA-Cage). A 1.0-Nm moment was applied to the primary C5-6 ACDF model to generate total C2-T1 range of motions (ROMs). Subsequently, a displacement load was applied to all RS models to match the total C2-T1 ROMs of the primary ACDF model. RESULTS: The ZOP-Cage model showed lower biomechanical responses including ROM, intradiscal pressure, maximum von Mises stress in discs, and facet joint force in adjacent segments compared to the Cage-Cage model. The CDA-Cage model exhibited the lowest biomechanical responses and ROM ratio at adjacent segments among all RS models, closely approached or lower than those in the primary ACDF model in most motion directions. Additionally, the maximum von Mises stress on the C3-4 and C6-7 discs increased in the Cage-Cage and ZOP-Cage models but decreased in the CDA-Cage model when compared to the primary ACDF model. CONCLUSION: The CDA-Cage construct had the lowest biomechanical responses with minimal kinematic change of adjacent segments. ZOP-Cage is the next best choice, especially if CDA is not suitable. This study provides a biomechanical reference for clinical hybrid RS decision-making to reduce the risk of ASD recurrence.

Hydrogel and Nanomedicine-Based Multimodal Therapeutic Strategies for Spinal Cord Injury.

Spinal cord injury (SCI) is a severe neurodegenerative disease caused by mechanical and biological factors, manifesting as a loss of motor and sensory functions. Inhibition of injury expansion and even reversal of injury in the acute damage stage of SCI are important strategies for treating this disease. Hydrogels and nanoparticle (NP)-based drugs are the most effective, widely studied, and clinically valuable therapeutic strategies in the field of repair and regeneration. Hydrogels are 3D flow structures that fill the pathological gaps in SCI and provide a microenvironment similar to that of the spinal cord extracellular matrix for nerve cell regeneration. NP-based drugs can easily penetrate the blood-spinal cord barrier, target SCI lesions, and are noninvasive. Hydrogels and NPs as drug carriers can be loaded with various drugs and biological therapeutic factors for slow release in SCI lesions. They help drugs function more efficiently by exerting anti-inflammatory, antioxidant, and nerve regeneration effects to promote the recovery of neurological function. In this review, the use of hydrogels and NPs as drug carriers and the role of both in the repair of SCI are discussed to provide a multimodal strategic reference for nerve repair and regeneration after SCI.

Advances in epigenetic research of adolescent idiopathic scoliosis and congenital scoliosis.

Scoliosis is a three-dimensional structural deformity of the spine; more than 80% of scoliosis has no specific pathogenesis but is understood to be closely related to genetic, hormonal, and environmental factors. In recent years, the epigenetic alterations observed in scoliosis have been analyzed in numerous studies to determine the pathogenesis and progression of this condition, however, there is currently no comprehensive review of the epigenetic factors to date. We searched PubMed, Embase, and Web of Science databases for relative studies without language and date restrictions in March 2023. Twenty-five studies were included in this review and analyzed from the four main aspects of epigenetic alteration: DNA methylation, non-coding RNAs, histone modifications, and chromatin remodeling. The relationship between DNA methylation, non-coding RNAs, and scoliosis was considerably reported in the literature, and the corresponding related signaling pathways and novel biomarkers observed in scoliosis provide insights into innovative prevention and treatment strategies. However, the role of histone modifications is rarely reported in scoliosis, and few studies have investigated the relationship between scoliosis and chromatin remodeling. Therefore, these related fields need to be further explored to elucidate the overall effects of epigenetics in scoliosis.

Comparison of the Radiographic and Clinical Outcome Changes in Patients With Spinal Deformity Before and After Stretching DanceExercise: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to compare radiographic and clinical outcomes of scoliosis and thoracic hyperkyphosis before and after stretching-based exercises. METHODS: Embase, PubMed, Cochrane Library, Web of Science, and Scopus databases were comprehensively searched for relevant studies from their inception to June 2022. Radiographic outcomes, including the Cobb angle of the main curve and thoracic kyphosis, and clinical outcomes, including the angle of trunk rotation (ATR), chest expansion, Numeric Rating Scale (NRS), and Scoliosis Research Society-22 Patient Questionnaire (SRS-22), were extracted. Pooled and subgroup analyses were performed using random or fixed-effects models based on I2 heterogeneity. RESULTS: In total, 334 patients from ten studies, including 255 patients with scoliosis and 79 patients with thoracic hyperkyphosis, were included in the meta-analysis. After stretching, the pooled results showed that the Cobb angle of the main curve and thoracic kyphosis significantly decreased (P < 0.001) in patients with scoliosis, and thoracic kyphosis, respectively. Angle of trunk rotation (ATR) decreased significantly (P = 0.003), and chest expansion improved significantly (P = 0.04) after stretching-based exercise. In addition, our pooled results showed that the NRS score was significantly reduced (P < 0.001) and that the SRS-22 scores of mental health (P = 0.003) and self-perceived image (P < 0.001) were significantly increased after stretching. CONCLUSIONS: Partial correction can be achieved using stretching-based exercises. Moreover, stretching-based exercises can reduce pain in patients and improve their quality of life. However, the optimal duration required further elucidation.

The Incidence, Changes and Treatments of Cervical Deformity After Infection and Inflammation.

A healthy cervical spine with normal movement is the basis of many daily activities and is essential for maintaining a good quality of life. However, the alignment, fusion, and structure of the cervical spine can change for various reasons, leading to cervical deformity, mainly kyphosis. Approximately 5%‒20% of spinal infections in the cervical spine cause cervical deformity. The deformity can recover early; however, the disease's long-term existence or the continuous action of abnormal stress may lead to intervertebral fusion and abnormal osteophytes. Many gaps and controversies exist regarding infectious cervical deformities, including a lack of clear definitions and an acceptable classification system thereby requiring further research. Moreover, there is no consensus on the indications for postinfectious cervical deformity associated with Mycobacterium tuberculosis, Staphylococcus aureus, and Brucellosis. Therefore, we reviewed and discussed the incidence, clinical manifestations, changes, and treatment of infectious and inflammatory secondary cervical deformities from common to rare to provide a theoretical basis for clinical decision-making.

Surgical Treatment of Scoliosis Lenke Type 5, Anterior Versus Posterior, Which Approach is Better?: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: This study aimed to compare the radiographical and clinical outcomes between anterior spinal fusion (ASF) and posterior spinal fusion (PSF) in Lenke type 5 adolescence idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: PSF has been the standard operation for adolescence idiopathic scoliosis. ASF can also achieve a good curve correction effect with fewer fusion segments and minor invasion of paraspinal structures. MATERIALS AND METHODS: A systematic literature research was conducted in PubMed, Embase, Cochrane Library, and Web of Science. Use meta-analysis to compare the changes of thoracolumbar/lumbar and thoracic curves and other important outcomes between ASF and PSF. RESULTS: A total of 427 ASF and 392 PSF patients from 12 studies were included. There was no significant difference in the correction degree of thoracolumbar/lumbar and thoracic curve between ASF and PSF ( P >0.05), except for PSF had more compensatory correction degree of thoracic curve at postoperation ( P <0.05). Besides, the loss of correction in thoracic curve in PSF at the last follow-up was significantly less than that in ASF ( P <0.05). PSF presented larger change values of thoracic kyphosis and lumbar lordosis at the last follow-up ( P <0.05). PSF showed a better effect in correcting trunk shift distance at the postoperation ( P <0.05) but less trunk shift distance correction from postoperation to last follow-up ( P <0.05). There was no significant difference in the incidence of proximal junctional kyphosis and estimated blood loss between the two approaches ( P >0.05). Moreover, ASF showed fewer fusion segments, but longer operation and hospital stay time ( P <0.05). CONCLUSION: ASF is capable of achieving similar correction in coronal curve and balance as PSF with fewer fusion segments. Spine surgeons should select an appropriate approach tailored to individual patients needs while considering procedural risks and benefits. LEVEL OF EVIDENCE: Level II.

OLIF versus ALIF: Which is the better surgical approach for degenerative lumbar disease? A systematic review.

PURPOSE: The aim of this study was to compare the clinical and radiographical outcomes between OLIF and ALIF in treating lumbar degenerative diseases. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library for relevant studies. Changes in disc height (DH), segmental lordosis angle (SLA), lumbar lordosis (LL), visual analogue scale (VAS) score, and Oswestry disability index (ODI) between baseline and final follow-up, along with other important surgical outcomes, were assessed and analysed. Data on the global fusion rate and main complications were collected and compared. RESULTS: Approximately, 2041 patients from 36 studies were included, consisting of 1057 patients who underwent OLIF and 984 patients who underwent ALIF. The results reveal no significant difference in DH, SLA, VAS score, and ODI between the two groups (all P > 0.05). The operation time, estimated blood loss, and length of hospital stay were also comparable between the two groups. Over 90% of the fusion rate was achieved in both groups. The OLIF group showed a higher complication rate than the ALIF group (OLIF 18.83% vs ALIF 7.32%). CONCLUSIONS: OLIF leads to a higher complication rate, with the most notable complication being cage subsidence. Both OLIF and ALIF are effective treatments for degenerative lumbar diseases and have similar therapeutic effects. ALIF was expected to be more expensive for patients because of the necessity of involving vascular surgeons.

The Role of Microglia/Macrophages Activation and TLR4/NF-κB/MAPK Pathway in Distraction Spinal Cord Injury-Induced Inflammation.

Distraction spinal cord injuries (DSCIs) often occur as the neurological complication of distraction forces following the implantation of internal fixation devices during scoliosis correction surgery. However, the underlying mechanism behind these injuries remains unclear. The present study aimed to explore the activation of microglia and macrophages, as well as changes in TLR4-mediated NF-κB and MAPK pathway activity after DSCIs in Bama miniature pigs. Prior to surgical intervention, the pigs were randomly divided into three groups: the sham group, the complete distraction spinal cord injury (CDSCI) group, and the incomplete distraction spinal cord injury (IDSCI) group. After surgery, the Tarlov scale and individual limb motor scale (ILMS) were used to evaluate changes in the pigs' behavior. All pigs were euthanized 7 days after surgery, and histopathological examinations of the spinal cord tissues were performed. Immunohistochemistry was used to detect Caspase-3 expression in the anterior horn of spinal gray matter tissues. Immunofluorescence staining was utilized to assess the M1/M2 phenotype changes in microglia/macrophages and NF-κB P65 expression in central DSCI lesions, while western blotting was performed to determine the expression of TLR4/NF-κB/MAPK pathway-related proteins. The results of the present study showed that the Tarlov and ILMS scores decreased significantly in the two DSCI groups compared with the sham group. Hematoxylin and eosin (HE) and Nissl staining revealed that the tissue structure and nerve fiber tracts in the distracted spinal cord tissues were destroyed. Both DSCI groups showed the number of survived neurons decreased and the Caspase-3 expression increased. The results of the immunofluorescence staining indicated that the CD16 and CD206 expression in the microglia/macrophages increased. Between the two DSCI groups, the CDSCI group showed increased CD16 and decreased CD206 expression levels. The intensity of the fluorescence of NF-κB P65 was found to be significantly enhanced in pigs with DSCIs. Moreover, western blot results revealed that the expression of TLR4, p-IκBα, NF-κB P65, p-JNK, p-ERK, and p-P38 proteins increased in spinal cord tissues following DSCI. The present study was based on a porcine DSCI model that closely mimicked clinical DSCIs while clarifying DSCI-associated neuroinflammation mechanisms, in turn providing evidence for identifying potential anti-inflammatory targets.

Enhanced production of ε-poly-L-lysine by immobilized Streptomyces ahygroscopicus through repeated-batch or fed-batch fermentation with in situ product removal.

ε-Poly-L-lysine (ε-PL) is a naturally-occurring L-lysine homopolymer having a broad-spectrum antimicrobial activity and used widely as a food preservative. In the present study, the combined use of immobilization and in situ product removal (ISPR) was evaluated for the production of ε-PL by Streptomyces ahygroscopicus GIM8. Results showed that ε-PL production in the flask cultures decreased from 0.84 to 0.38-0.56 g/L upon immobilization on loofah sponge with different amounts (0.5-3 g in 50 mL medium in a flask). By applying continuous ISPR to the immobilized flask cultures, ε-PL production as high as 3.51 g/L was obtained compared to 0.51 g/L of the control. A satisfactory titer of 1.84 g/L ε-PL could also be achieved with intermittent ISRP (three cycles of ISPR operation during cultivation). Further investigation showed that low levels of ε-PL retained in the broth appeared to favor its biosynthesis. In the repeated-batch fermentation in a 5 L immobilized bioreactor, with continuous ISPR, the final average ε-PL concentration and productivity were 3.35 g/L and 0.797 g/L/day, respectively, and 3.18 g/L and 0.756 g/L/day for the alternative (intermittent ISPR), in comparison to 1.16 g/L and 0.277 g/L/day with no ISPR usage. In the fed-batch fermentation with immobilized cells, the combined use of intermittent ISPR and extra nutrient feeding increased ε-PL concentration and productivity up to 24.57 g/L and 9.34 g/L/day. The fermentation processes developed could serve as an effective approach for ε-PL production and, moreover, the combination could greatly simplify downstream processing for ε-PL separation and purification.

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.