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Background: The current standard of care for intervertebral disc (IVD) herniation, surgical discectomy, does not repair annulus fibrosus (AF) defects, which is partly due to the lack of effective methods to do so and is why new repair strategies are widely investigated and tested preclinically. There is a need to develop a standardized IVD injury model in large animals to enable comparison and interpretation across preclinical study results. The purpose of this study was to compare in vivo IVD injury models in sheep to determine which annulus fibrosus (AF) defect type combined with partial nucleus pulposus (NP) removal would better mimic degenerative human spinal pathologies. Methods: Six skeletally mature sheep were randomly assigned to one of the two observation periods (1 and 3 months) and underwent creation of 3 different AF defect types (slit, cruciate, and box‐cut AF defects) in conjunction with 0.1 g NP removal in three lumbar levels using a lateral retroperitoneal surgical approach. The spine was monitored by clinical CT scans pre‐ and postoperatively, at 2 weeks and euthanasia, and by magnetic resonance imaging (MRI) and histology after euthanasia to determine the severity of degeneration (disc height loss, Pfirrmann grading, semiquantitative histopathology grading). Results: All AF defects led to significant degenerative changes detectable on CT and MR images, produced bulging of disc tissue without disc herniation and led to degenerative and inflammatory histopathological changes. However, AF defects were not equal in terms of disc height loss at 3 months postoperatively; the cruciate and box‐cut AF defects showed significantly decreased disc height compared to their preoperative height, with the box‐cut defect creating the greatest disc height loss, while the slit AF defect showed restoration of normal preoperative disc height. Conclusions: The tested IVD injury models do not all generate comparable disc degeneration but can be considered suitable IVD injury models to investigate new treatments. Results of the current study clearly indicate that slit AF defect should be avoided if disc height is used as one of the main outcomes; additional confirmatory studies may be warranted to generalize this finding. [ABSTRACT FROM AUTHOR]

Abstract Background The current standard of care for intervertebral disc (IVD) herniation, surgical discectomy, does not repair annulus fibrosus (AF) defects, which is partly due to the lack of effective methods to do so and is why new repair strategies are widely investigated and tested preclinically. There is a need to develop a standardized IVD injury model in large animals to enable comparison and interpretation across preclinical study results. The purpose of this study was to compare in vivo IVD injury models in sheep to determine which annulus fibrosus (AF) defect type combined with partial nucleus pulposus (NP) removal would better mimic degenerative human spinal pathologies. Methods Six skeletally mature sheep were randomly assigned to one of the two observation periods (1 and 3 months) and underwent creation of 3 different AF defect types (slit, cruciate, and box‐cut AF defects) in conjunction with 0.1 g NP removal in three lumbar levels using a lateral retroperitoneal surgical approach. The spine was monitored by clinical CT scans pre‐ and postoperatively, at 2 weeks and euthanasia, and by magnetic resonance imaging (MRI) and histology after euthanasia to determine the severity of degeneration (disc height loss, Pfirrmann grading, semiquantitative histopathology grading). Results All AF defects led to significant degenerative changes detectable on CT and MR images, produced bulging of disc tissue without disc herniation and led to degenerative and inflammatory histopathological changes. However, AF defects were not equal in terms of disc height loss at 3 months postoperatively; the cruciate and box‐cut AF defects showed significantly decreased disc height compared to their preoperative height, with the box‐cut defect creating the greatest disc height loss, while the slit AF defect showed restoration of normal preoperative disc height. Conclusions The tested IVD injury models do not all generate comparable disc degeneration but can be considered suitable IVD injury models to investigate new treatments. Results of the current study clearly indicate that slit AF defect should be avoided if disc height is used as one of the main outcomes; additional confirmatory studies may be warranted to generalize this finding.

BACKGROUND: Studies have shown that the endplate injuries in patients with osteoporotic vertebral compression fracture are related to the intradiscal cement leakage after percutaneous vertebral augmentation. OBJECTIVE: To investigate the correlation between preoperative magnetic resonance imaging findings and intradiscal cement leakage after percutaneous vertebral augmentation, and to analyze whether endplate fractures and adjacent intervertebral disc injuries affect the incidence of intradiscal cement leakage. METHODS: Totally 182 patients with single-level osteoporotic vertebral compression fractures admitted to the Affiliated Hospital of Xuzhou Medical University from September 2018 to December 2019 were selected, of which 110 received percutaneous kyphoplasty treatment, 72 cases received percutaneous vertebroplasty treatment. According to the preoperative magnetic resonance imaging images, the condition of the adjacent intervertebral disc injury and endplate fracture of the fractured vertebral body was evaluated. According to whether there is intradiscal cement leakage after the operation, the patients were divided into a leakage group (n=32) and a non-leakage group (n=150). A univariate analysis was performed on the correlation between the patient’s age, gender, surgical spinal level, surgical method, endplate fracture, adjacent intervertebral disc injury and intradiscal cement leakage, and then a multivariate binary logistics regression model analysis was performed. The study was approved by the Medical Ethics Committee of the Affiliated Hospital of Xuzhou Medical University. RESULTS AND CONCLUSION: (1) Of the 182 patients, 63 had endplate fractures and 98 had adjacent intervertebral disc injuries. In all patients, 32 cases of intradiscal cement leakage occurred after percutaneous vertebral augmentation; the leakage rate of the endplate fracture group was higher than that of the non-endplate fracture group (P < 0.05), and the leakage rate of the intervertebral disc injury group was higher than that of the non-intervertebral disc injury group (P < 0.05). (2) The results of univariate analysis showed that intradiscal cement leakage was related to surgical method (P < 0.05), which was not related to age, gender, and surgical spinal level (P > 0.05). (3) The binary logistics regression analysis showed that the endplate fracture was the independent risk factor for intradiscal cement leakage after percutaneous vertebral augmentation; adjacent intervertebral disc injury, age, gender, surgical method, and surgical spinal level were not the risk factors for intradiscal cement leakage. (4) Related analysis showed that there was a significant correlation between the endplate fracture and the intervertebral disc injury (r=0.47, P=0.000). (5) The results showed that the endplate fracture found in the preoperative magnetic resonance imaging was a risk factor for intradiscal cement leakage, and the intervertebral disc injury was not the influence factor of intradiscal cement leakage; the intervertebral disc injury was significantly related to the endplate fracture in osteoporotic vertebral compression fractures patients. [ABSTRACT FROM AUTHOR]

Study Design: A multi-cohort, case-control rodent study.Purpose: Investigate the long-term behavioural, histologic and radiologic consequences on the complete lumbar spine of L4/5 intervertebral disc (IVD) injury in mice and determine if increased physical activity mitigates the observed changes.Methods: Cohorts of 2-month-old CD1 female mice underwent a single ventral puncture of the L4/5 IVD. 0.5-, 3- or 12-months after injury, general health (body weight and locomotor capacity), behavioural signs of axial discomfort (tail suspension, grip strength and FlexMaze assays) and radiating pain (von Frey and acetone tests) were assessed. Experimental groups with free access to an activity wheel in their home cages were including in the 12-month cohort. Lumbar disc status was determined using colorimetric staining and radiologic (X-ray and T2-MRI) analysis. Innervation was measured by immunoreactivity for PGP9.5 and calcitonin gene-related peptide.Results: No changes in general health or persistent signs of axial discomfort were observed up to one year post-injury. In contrast, signs of radiating pain developed in injured mice at 3 months post-injury, persisted up to 12 months and were reversed by long-term physical activity. At 12-months post-injury, degeneration was observed in non-injured lumbar discs. Secondary degenerating IVDs were similar to the injured discs by X-ray (narrowing) and T2-MRI (internal disc disruption) but did not show abnormal innervation. Increased physical activity had no impact on mechanically injured IVDs, but attenuated disc narrowing at other lumbar levels.Conclusions: Mechanical injury of L4/5-IVDs induces delayed radiating pain and degeneration of adjacent discs; increased physical activity positively mitigated both. [ABSTRACT FROM AUTHOR]

Abstract Background The endplate-intervertebral disc (IVD) complex is closely interrelated with the vertebral body (VB) in the structural integrity of the anterior spinal column, including biomechanical and biological functions. Endplate and IVD injuries are usually found in association with vertebral fractures (VFs); however, little is known about their relevance to the healing of osteoporotic VFs (OVFs). The first purpose of this study was to evaluate the incidence and occurrence pattern of endplate and IVD injuries associated with single- and acute-OVFs, and the second was to evaluate the influence of endplate and IVD injuries on the occurrence of delayed union. Methods Endplate and IVD injuries associated with single- and acute-OVFs were retrospectively evaluated using magnetic resonance imaging (MRI). Vertebrae of 168 patients were included in the study. The occurrence rate and type of endplate and IVD injuries were radiologically evaluated, and the association between endplate and IVD injuries was statistically analyzed. Vertebrae of 85 patients, who received conservative treatment for acute OVFs, were included in the study and classified into two groups, union and delayed union, at 6 months after injury. To identify factors predicting delayed union, uni- and multivariate statistical analyses were performed. Vertebral MRI signal alternation patterns and endplate and IVD injuries were included as candidate factors in the logistic model. Results In association with OVFs, endplate injuries were observed in 103 of the 168 vertebrae (61%), and IVDs lesions were observed in 101 of 168 OVFs (60%); the occurrence of both injuries was significantly associated. Although no significant association with endplate and IVD injuries was identified, multivariate analysis demonstrated that intravertebral signal alternation (focal high signal intensity) and posterior wall injury were independent risk factors that predicted delayed union. Conclusions The results of this study showed that endplate and IVD injuries were found in approximately 60% of single and acute OVFs. These results suggest that fracture healing of OVFs would be mainly attributed to vertebral factors, including mechanical stress and metabolic status, among the three components of the anterior spinal column.

Background Context: Degenerative disc disease (DDD) is associated with longitudinal remodeling of paravertebral tissues. Although chronic vertebral changes in advanced stages of DDD are well-studied, very little data exists on acute vertebral bone remodeling at the onset and progression of DDD.Purpose: To longitudinally characterize bony remodeling in a rodent model of disc injury-induced DDD.Study Design: In vivo animal study involving a rat annulus fibrosus injury model of DDD.Methods: Eight female Lewis rats were assigned to intervertebral disc (IVD) injury (Puncture) or sham surgery (Sham). All rats underwent anterior, transperitoneal approach to the lumbar spine, and Puncture rats underwent annulus fibrosus injury at the L3-L4 and L5-L6 IVDs (n = 8 per group). Live micro computed tomography imaging (10-μm voxel size) was performed 1 week before surgery and postoperatively at 2-week intervals up to a 12-week endpoint. Bone morphology and densitometry of the cranial vertebral body and bony endplate were analyzed and reported with respect to the preoperative baseline scan. Sagittal Safranin-O/Fast-Green and Toluidine Blue histology evaluated using the Rutges IVD score and a custom vertebral endplate score.Results: Vertebral trabecular tissue mineral density (TMD), vertebral trabecular spacing, endplate TMD, and endplate apparent bone mineral density were all significantly greater in Puncture compared with Sham at 4 weeks and each subsequent timepoint. Puncture rats exhibited marginally lower endplate total volume. Anterior endplate osteophyte formation and central physeal ossification were observed in Puncture rats. Endpoint histological analysis demonstrated moderate evidence of IVD degeneration, indicating that vertebral bone adaptation occurs in the acute phases of DDD onset and progression.Conclusions: Annulus injury-induced DDD leads to acute and progressive changes to the morphology and densitometry of bone in the adjacent vertebral bodies and endplates. [ABSTRACT FROM AUTHOR]

Background Context: Chronic inflammation is an important component of intervertebral disc (IVD) degeneration, but there is limited knowledge about the identity and source of inflammatory cells involved with the degenerative processes. Macrophages can exhibit multiple phenotypes and are known inflammatory regulators in many tissues, but their phenotypes have not been characterized in IVD degeneration.Purpose: We aimed to characterize accumulation and localization of macrophages in IVD degeneration.Study Design/setting: This is an exploratory study to characterize macrophage phenotypes in human cadaver IVDs and the effects of injury and degeneration using multiple immunohistochemistry methods.Outcome Measures: Percent positivity of immunohistochemical markers specific for CCR7, CD163, and CD206, and qualitative assessments of dual immunofluorescence and immunostaining localization were the outcome measures.Methods: Macrophages were identified in human cadaveric IVDs with immunohistochemistry using cell surface markers CCR7, CD163, and CD206, which are associated with proinflammatory M1, remodeling M2c, and anti-inflammatory M2a phenotypes, respectively. Variations in the accumulation and localization of macrophage markers with degenerative grade across subjects and within donors are described.Results: Cells expressing all three macrophage markers were found in all degenerative IVDs, but not in the healthiest IVDs. Cells expressing CCR7 and CD163, but not CD206, significantly increased with degenerative grade. Many cells also co-expressed multiple macrophage markers. Across all degenerative grades, CCR7+ and CD163+ were significantly more present in unhealthy nucleus pulposus (NP), annulus fibrosus (AF), and end plate (EP) regions exhibiting structural irregularities and defects. Positively stained cells in the NP and AF closely resembled resident IVD cells, suggesting that IVD cells can express macrophage cell surface markers. In the EP, there were increasing trends of positively stained cells with atypical morphology and distribution, suggesting a source for exogenous macrophage infiltration into the IVD.Conclusions: Chronic inflammatory conditions of IVD degeneration appear to involve macrophages or macrophage-like cells, as expression of multiple macrophage markers increased with degeneration, especially around unhealthy regions with defects and the EP. Knowledge of macrophage phenotypes and their localization better elucidates the complex injury and repair processes in IVDs and may eventually lead to novel treatments. [ABSTRACT FROM AUTHOR]

Thoracolumbar burst fracture is one of the most common and most studied injuries of the spine. Radiography and quantitative discomanometry have previously demonstrated that intervertebral discs adjacent to a burst fracture were disrupted; however, there have been conflicting data on the properties of the next-adjacent discs. Also, no data exists on the localization of injury within each disc. The objective of this study is to use an in vitro biomechanical design to examine the flexibility differences of intervertebral discs adjacent and next-adjacent to burst fracture vertebrae. Ten cadaveric thoracolumbar (T11–L3) spines with L1 burst fracture included adjacent (T12–L1, L1–L2) and next-adjacent (T11–T12, L2–L3) intervertebral discs. The bending flexibilities (μm/N) of each disc under 50 N of compression were determined at 25 points: the center point, along with the combinations of three radii (1 cm, 2 cm, 3 cm) and eight angles. The overall flexibility of each disc and the presence of any regional differences were then evaluated. Across all radii, the T11μT12 disc was statistically less flexible than the other three discs (p < 0.01). The difference between the flexibilities of the average anterior region and the average posterior region was significant at many 2-cm and all 3-cm radii; this difference was greater in the T12–L1 disc than in any of the other three discs. Thus, the upper next-adjacent intervertebral disc (T11–T12) was not as susceptible to mechanical disruption as were the other three discs. The anterior region of each disc may also have a higher propensity for mechanical disruption than the posterior region, especially at larger radii. [ABSTRACT FROM AUTHOR]

Study Design: A single-institution retrospective study of a cohort of patients who underwent internal fixation spine surgery for thoracolumbar burst fracture (TLBF)., Objective: To observe the imaging manifestations of intervertebral disc changes in TLBF, to analyze the relationship between the degree of disc injury and the Cobb angle increase., Methods: We retrospectively analyzed the data of patients who underwent short-segment pedicle screw instrumentation in the spinal surgery department of a single hospital between January 2014 and December 2017 ( n = 90). According to the magnetic resonance imaging characteristics of the superior intervertebral disc tissue of the injured vertebrae before the operation, the intervertebral disc injury was divided into three types, which was used for group allocation: group A, uninjured intervertebral disc group; group B, mild intervertebral disc injury group; and group C, severe intervertebral disc injury group. The main imaging results of the three groups Cobb, IVA, IHI, AHIV, and VAS were compared among groups., Results: Ninety patients were included in the study ( n = 38, 32, and 20, in groups A, B, and C, respectively). There was no statistically significant difference in demographics among the three groups ( p > .05). 1-year post-surgery, the Cobb angle in group C differed significantly from that in groups A and B ( p < .01). There was a significant difference in Cobb angle between groups A and B after internal fixation was removed for 6 months. At 1-year post-surgery, the IHI group C differed significantly from groups A and B ( p < .01), while groups A and B were similar ( p = .102); however, at 6 months after the internal fixation was removed, the IHI differed significantly between these two groups, also the AHIV between groups A and B was statistically significant ( p < .01). The VAS pain score was similar among the three groups. Pearson's test showed that the increase in the Cobb angle was moderately correlated with IVA and IHI, and weakly correlated with AHIV., Conclusion: For TLBF with an intervertebral disc injury, the presurgical degree of intervertebral disc injury is the main reason for the post-surgery increase in the Cobb angle. Thus, diagnosis and treatment of this kind of patient require attention to the risk of spinal deformity.

Although great strides have been made in medical technology, low back/neck pain and intervertebral disc degeneration initiated from disc degenerative disease remains a clinical challenge. Within the field of regenerative medicine therapy, we have sought to improve the biomechanical transformation of spinal fusion procedures conducted using biodegradable porous implants. Specifically, we have focused on developing mechanically strong bioceramic cages for spinal fusion and functional recovery. Herein, we fabricated the akermanite (AKE) ceramic-based porous cages using low-melting bioactive glass (BG) and 3D printing technology. The osteogenic cell adhesion on the cages was evaluated in vitro, and the spinal fusion was tested in the intervertebral disc trauma model. The results indicated that incorporation of 15% or 30% BG into AKE (i.e., AKE/BG15 and AKE/BG30) could enhance the compressive strength of bioceramic cages by 2- or 5-fold higher than the pure AKE cages (AKE/BG0). In comparison with porous β-tricalcium phosphate cages, the surface of AKE/BG15 and AKE/BG30 cages greatly promoted the growth and alkaline phosphatase expression of osteogenic cells. Histological and biomechanical analysis showed that the AKE/BG15 and AKE/BG30 readily stimulated the new bone tissue growth and improved the spinal biomechanics recovery. In the AKE/BG15 and AKE/BG30 cage groups, 4-6 of the rabbits demonstrated a successful fusion. In contrast, only 0-1 of the initial seeded AKE/BG0 and tricalcium phosphate cages resulted in fusion at 12 weeks post-operatively. In summary, the akermanite-based cages showed an increased bone regenerative effect within an intervertebral disc trauma model, and thus, provided a promising candidate for improving spinal fusion surgery., (Copyright © 2017 John Wiley & Sons, Ltd.)

Spinal trauma can cause simultaneous injury of intervertebral discs (IVD) and anterior longitudinal ligaments (ALL). Injury of IVD is an important factor causing intervertebral disc degeneration (IDD). However, the relationship between ALL injury and IDD has rarely been discussed. Therefore, the purpose of this study was to investigate the effects of ALL injury on degeneration of injured IVD. Thirty-two rabbits were randomly and evenly divided into four groups including sham group, Group A (simple IVD punctured), Group B (IVD punctured with half transverse injury of ALL), and Group C (IVD punctured with entirely transverse injury of ALL). Then, computed tomography, HE staining, intraoperative exploration, immunohistochemistry, and TUNEL staining were used in detecting the degenerative changes in corresponding IVD. At 2 weeks postoperatively, in response to the extent of ALL injury, the middle height of the punctured intervertebral space was reduced. The IVD structure was disorganized and the number of IVD cells was decreasing. The percentage of IL-1β- and TNF-α-immunopositive cells was increased and the percentage of TUNEL-positive IVD cells was also increased. There was a significant difference between Group C and the other groups in the results of immunohistochemistry and TUNEL staining ( P <0.05). At 8 weeks postoperatively, the middle height of intervertebral space was significantly lower in Group C than in other groups ( P <0.05). Intraoperative exploration found that there was obvious instability of intervertebral space in Group C. Compared with 2 weeks postoperation, the pathological changes were severe. The percentage of IL-1β- and TNF-α-immunopositive cells was decreased and the percentage of TUNEL-positive cells was increased in the corresponding groups. There was a significant difference between Group C and the other groups in the results of immunohistochemistry and TUNEL staining ( P <0.05). These findings indicate that IVD injury companied with completed ALL injury might cause obvious spinal instability, which might correspond to severe IDD., Competing Interests: None., (IJCEP Copyright © 2018.)