Disc degeneration spreads: long-term behavioural, histologic and radiologic consequences of a single-level disc injury in active and sedentary mice.

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.

Endplate and intervertebral disc injuries in acute and single level osteoporotic vertebral fractures: is there any association with the process of bone healing?

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.

[Effectiveness of injured vertebra fixation with inclined-long pedicle screws combined with interbody fusion for thoracolumbar fracture dislocation with disc injury].

Objective: To investigate the effectiveness of injured vertebra fixation with inclined-long pedicle screws combined with interbody fusion for thoracolumbar fracture dislocation with disc injury. Methods: Between January 2017 and June 2022, 28 patients with thoracolumbar fracture dislocation with disc injury were underwent posterior depression, the injured vertebra fixation with inclined-long pedicle screws, and interbody fusion. There were 22 males and 6 females, with a mean age of 41.4 years (range, 22-58 years). The causes of injury included falling from height in 18 cases, traffic accident in 5 cases, and bruise in 5 cases. Fracture segment included 1 case of T 11, 7 cases of T 12, 9 cases of L 1, and 11 cases of L 2. According to the American Spinal Injury Association (ASIA) scale, the spinal injuries were graded as grade A in 4 cases, grade B in 2 cases, grade C in 11 cases, and grade D in 11 cases. Preoperative spinal canal encroachment ratio was 17.7%-75.3% (mean, 44.0%); the thoracolumbar injury classification and severity score (TLICS) ranged from 9 to 10 (mean, 9.9). Seventeen patients were associated with other injuries. The time from injury to operation ranged from 1 to 4 days (mean, 2.3 days). The perioperative indicators (operation time, intraoperative blood loss, and the occurrence of complications), clinical evaluation indicators [visual analogue scale (VAS) score and Oswestry Disability Index (ODI)], radiologic evaluation indicators [anterior vertebral height ratio (AVHR), kyphosis Cobb angle (KCA), intervertebral space height (ISH), vertebral wedge angle (VWA), displacement angle (DA), and percent fracture dislocation displacement (PFDD)], neurological function, and interbody fusion were recorded. Results: The operation time was 110-159 minutes (mean, 130.2 minutes). The intraoperative blood loss was 200-510 mL (mean, 354.3 mL). All incisions healed by first intention, and no surgical complications such as wound infection or hematoma occurred. All patients were followed up 12-15 months (mean, 12.7 months). The chest and lumbar pain significantly relieved, VAS scores and ODI after operation were significantly lower than those before operation, and further decreased with the extension of postoperative time, with significant differences ( P<0.05). At last follow-up, the ASIA classification of neurological function of the patients was grade A in 3 cases, grade B in 1 case, grade C in 1 case, grade D in 10 cases, and grade E in 13 cases, which was significantly different from preoperative one ( Z=-4.772, P<0.001). Imaging review showed that AVHR, KCA, ISH, VWA, DA, and PFDD significantly improved at 1 week, 3 months and last follow-up ( P<0.05). There was no significant difference between different time points after operation ( P>0.05). At last follow-up, according to the modified Brantigan score, all patients achieved good intervertebral bone fusion, including 22 complete fusion and 6 good intervertebral fusion with a few clear lines. No complications such as internal fixation failure or kyphosis occurred during follow-up. Conclusion: The injured vertebra fixation with inclined-long pedicle screws combined with interbody fusion is an effective treatment for thoracolumbar fracture dislocation with disc injury, which can correct the fracture dislocation, release the nerve compression, restore the injured vertebral height, and reconstruct spinal stabilization.

[Herniation of intervertebral disc into thoracolumbar fracture vertebral body leads to malunion of fracture and decrease of intervertebral space height].

OBJECTIVE: To analyze the clinical characteristics of intervertebral disc tissue injury and herniation into the vertebral body in thoracolumbar fracture on fracture healing, vertebral bone defect volume and intervertebral space height. METHODS: From April 2016 to April 2020, a total of 140 patients with thoracolumbar single vertebral fracture combined with upper intervertebral disc injury treated with pedicle screw rod system reduction and internal fixation in our hospital. There were 83 males and 57 females, aged from 19 to 58 years old, with an average age of (39.33±10.26) years old. All patients were followed up regularly 6 months, 12 months and 18 months after surgery. The patients with injured intervertebral disc tissue not herniated into the fractured vertebral body were the control group, and the patients with injured intervertebral disc and herniated into the fractured vertebral body were the observation group. By detecting the thoracolumbar AP and lateral X-ray films, CT and MRI of the thoracolumbar segment at different follow-up time, calculate the changes of the wedge angle of the fractured vertebral body, the sagittal kyphosis angle and the height of the superior adjacent intervertebral space, the changes of the fracture healing and bone defect volume after the reduction of the vertebral body, and the changes of the intervertebral disc degeneration grade. The prognosis was evaluated by visual analogue scale(VAS) and Oswestry disability index(ODI). Finally, the differences of the above results among different groups were comprehensively analyzed. RESULTS: All the patients had normal wound healing without complications. A total of 87 patients received complete follow-up data, at least 18 months after internal fixation. Thoracolumbar AP and lateral X-ray films showed that 18 months after the reduction and internal fixation operation, the vertebral wedge angle, sagittal kyphosis angle and the height of the upper adjacent intervertebral space in the observation group were greater than those in the control group(P<0.05). CT scanning showed that the deformity of the fracture healed 12 months after the vertebral body reduction in the observation group and formed a "cavity" of bone defect connected with the intervertebral space, and its volume was significantly increased compared with that before (P<0.05). MRI scanning showed that the degeneration rate of injured intervertebral discs in the observation group was more serious than that in the control group 12 months after operation(P<0.05). However, there was no significant difference in VAS and ODI score at each time. CONCLUSION: Herniation of injured intervertebral disc tissue hernias into the fractured vertebral body leads to increased bone resorption defect volume around the fracture and forms a malunion "cavity" connected with the intervertebral space. This may be the main reason for the change of vertebral wedge angle, the increase of sagittal kyphosis angle and the decrease of intervertebral space height after removal of internal fixation devices.

Spinal injury rates and specific causation in motor vehicle collisions.

Motor vehicle collisions (MVCs) are a leading cause of acute spinal injuries. Chronic spinal pathologies are common in the population. Thus, determining the incidence of different types of spinal injuries due to MVCs and understanding biomechanical mechanism of these injuries is important for distinguishing acute injuries from chronic degenerative disease. This paper describes methods for determining causation of spinal pathologies from MVCs based on rates of injury and analysis of the biomechanics require to produce these injuries. Rates of spinal injuries in MVCs were determined using two distinct methodologies and interpreted using a focused review of salient biomechanical literature. One methodology used incidence data from the Nationwide Emergency Department Sample and exposure data from the Crash Report Sample System supplemented with a telephone survey to estimate total national exposure to MVC. The other used incidence and exposure data from the Crash Investigation Sampling System. Linking the clinical and biomechanical findings yielded several conclusions. First, spinal injuries caused by an MVC are relatively rare (511 injured occupants per 10,000 exposed to an MVC), which is consistent with the biomechanical forces required to generate injury. Second, spinal injury rates increase as impact severity increases, and fractures are more common in higher-severity exposures. Third, the rate of sprain/strain in the cervical spine is greater than in the lumbar spine. Fourth, spinal disc injuries are extremely rare in MVCs (0.01 occupants per 10,000 exposed) and typically occur with concomitant trauma, which is consistent with the biomechanical findings 1) that disc herniations are fatigue injuries caused by cyclic loading, 2) the disc is almost never the first structure to be injured in impact loading unless it is highly flexed and compressed, and 3) that most crashes involve predominantly tensile loading in the spine, which does not cause isolated disc herniations. These biomechanical findings illustrate that determining causation when an MVC occupant presents with disc pathology must be based on the specifics of that presentation and the crash circumstances and, more broadly, that any causation determination must be informed by competent biomechanical analysis.

Comparison of the Outcomes between AO Type B2 Thoracolumbar Fracture with and without Disc Injury after Posterior Surgery.

OBJECTIVE: The type AO B2 thoracolumbar fracture is a kind of flexion-distraction injury and the effect of disc injury on treatment results of patients with B2 fracture remains unclear. The objective of the current study was to compare and analyze the outcomes in AO Type B2 thoracolumbar fracture patients with and without disc injuries in terms of the Cobb angle of kyphosis, the incidence of complication, and the rate of implant failure. METHODS: This is a retrospective study. Of the 486 patients with thoracolumbar fractures who underwent posterior fixation, 38 patients with AO type B2 injuries were included. All the patients were divided into two groups according to changes in the adjoining discs. Disc injury group A included 17 patients and no disc injury group included 21 patients. Clinical and radiologic parameters were evaluated before surgery, after surgery, and at follow-up. Clinical outcomes included visual analogue scale (VAS) scores, incidence of complications, and incidence of implant failure. Radiologic assessment was accomplished with the Cobb angle (CA), local kyphosis (LK), percentage of anterior vertebral height (AVBH%), intervertebral disc height, and intervertebral disc angle. Fisher's precision probability tests were employed and chi square test were used to compare categorical variables. Paired sample t tests and independent-sample t tests were used to compare continuous data. RESULTS: Disc injury mainly involved the cranial disc (15/19, 78.9%). The mean follow-up period for the patients was 30.2 ± 20.1 months. No neurologic deterioration was reported in the patients at the last follow-up. Radiological outcomes at the last follow-up showed significant differences in the CA (18.59° ± 13.74° vs 8.16° ± 9.99°, P = 0.008), LK (12.74° ± 8.00° vs 6.55° ± 4.89°, P = 0.006), and %AVBH (77.16% vs 90.83%, P = 0.01) between the two groups.Implant failure occurred after posterior fixation in five patients with disc injury who did not undergo interbody fusion during the initial surgery. Additionally, in the subgroup analysis, interbody fusion in the implant failure group were significantly different than in the no implant failure group (0% vs 75%, P = 0.009). CONCLUSIONS: AO B2 fracture patients with disc injury have higher risk of complications, especially implant failure after posterior surgery. Interbody fusion should be considered in AO type B2 fracture patients with disc injury.

Intervertebral disc injury is the mainspring for the postoperative increase in Cobb Angle after thoracolumbar burst fracture.

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.

Comparison and optimization of sheep in vivo intervertebral disc injury model.

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.

Intradiscal Delivery of Anabolic Growth Factors and a Metalloproteinase Inhibitor in a Rabbit Acute Lumbar Disc Injury Model.

BACKGROUND: The purpose of our study was to examine the effect of controlled delivery of TGF-ß3, BMP-4, and TIMP-2 with a biocompatible biopolymer, chitosan, on an acutely injured intervertebral disc (IVD) in a rabbit model. METHODS: After conducting an in vitro analysis of the chondrogenic capacity of the biomolecule cocktail use (ie, TGF-ß3, BMP-4, and TIMP-2) and confirming stem cell viability in chitosan hydrogel, 15 New Zealand white rabbits underwent a lateral approach of the L1 to L4 IVDs. In each rabbit, the L2 to L3 IVD was left pristine, whereas the L1 to L2 and the L3 to L4 IVDs in each rabbit underwent nucleotomy via a 25-G needle, and the animal was subsequently randomized to no further treatment (defect only), chitosan alone, Chitosan + TGF-ß3 + BMP-4, or chitosan + TGF-ß3 + BMP-4 + TIMP-2. At 6 weeks after injury and intervention, the rabbits were killed and spines harvested to undergo quantitative T2 magnetic resonance imaging (MRI) and subsequent histologic analysis. RESULTS: In the in vitro analysis, cells treated with experimental media containing TGF-ß3, BMP-4, and TIMP-2 exhibited staining indicative of GAG production and began to exhibit a chondrocytic morphology. Quantitative T2 MRI mapping demonstrates that discs treated with chitosan, chitosan containing TGF-ß3 and BMP-4, or chitosan containing TGF-ß3, BMP-4, and TIMP-2 had consistently higher T2 relaxation times compared with defect-only discs. When the T2 relaxation times of each treatment group and defect-only discs were normalized to the healthy control disc, it was found that the T2 relaxation time of discs treated with chitosan containing TGF-ß3 and BMP-4 and discs treated with chitosan containing TGF-ß3, BMP-4, and TIMP-2 were significantly greater compared with defect-only discs (P = .048 and P = .013, respectively). Histologically, animals that received chitosan only, or chitosan with TGF-ß3 and BMP-4, showed a significantly higher intensity of Safranin-O staining (P = .016 and P = .02, respectively) compared with control discs, whereas the difference in staining intensity in animals that received chitosan loaded with TGF-ß3, BMP-4, and TIMP-2 failed to achieve significance (P = .161). CONCLUSIONS: A combination of chitosan, TGF-ß3, and BMP-4 was effective at promoting regeneration in an acute disc injury rabbit model, whereas TIMP-2 did not have a significant effect.

Prediction of MRI findings including disc injury and posterior ligamentous complex injury in neurologically intact thoracolumbar burst fractures by the parameters of vertebral body damage on CT scan.

OBJECTIVE: To formulate radiological indexes based on CT for further MRI examination to detect posterior ligamentous complex injury (PLC) or disc injury in thoracolumbar burst fractures without neurological deficit in the emergent setting. MATERIALS AND METHODS: Patients with a single thoracolumbar burst fracture and no neurological deficit were included into this study. Radiological indexes on CT included canal compromise (CC), anterior and posterior vertebral height ratio (PVH and AVH ratio), local kyphosis (LK) and regional kyphosis (RK). PLC and disc injury were assessed on MRI. Statistical analysis was performed to identify the predictive power for radiological indexes for any MRI findings either or both disc and PLC injury. RESULTS: Eighty-four patients were included in this study. According to MRI, patients with no PLC and disc injury were allocated into MRI finding negative group, others were defined as positive group. There was no significant difference in AVH ratio, PVH ratio and RK between these two groups. The CC and LK were significant higher in positive group than that in negative group (p < 0.001).The areas under receiver operating characteristic curve were 0.826 and 0.893 for CC and LK respectively and without significant difference. The best thresholds for CC and LK were 0.19 (sensitivity: 69.4%; specificity: 87.5%) and 14.00° (sensitivity: 83.3%; specificity: 83.3%), respectively. CONCLUSION: The presence of CC > 0.19 and/or LK > 14.00° on CT scan can predict MRI findings including PLC and disc injury. These thresholds may be the guideline for MRI examination in patients with neurologically intact thoracolumbar burst fracture in the emergent condition.

Degeneration of injured intervertebral discs affected by anterior longitudinal ligament injury in rabbits.

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-1ß- 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-1ß- 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.

Accumulation and localization of macrophage phenotypes with human intervertebral disc degeneration.

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.

Low-melt bioactive glass-reinforced 3D printing akermanite porous cages with highly improved mechanical properties for lumbar spinal fusion.

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 ß-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.

Dynamic adaptation of vertebral endplate and trabecular bone following annular injury in a rat model of degenerative disc disease.

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.

Sequential neurological improvements after conservative treatment in patients with complete motor paralysis caused by cervical spinal cord injury without bone and disc injury.

OBJECTIVE This study investigated neurological improvements after conservative treatment in patients with complete motor paralysis caused by acute cervical spinal cord injury (SCI) without bone and disc injury. METHODS This study was retrospective. The authors evaluated neurological outcomes after conservative treatment of 62 patients with complete motor paralysis caused by cervical SCI without bone and disc injury within 72 hours after trauma. The sequential changes in their American Spinal Injury Association Impairment Scale (AIS) grades were reviewed at follow-up 24-72 hours, 1 week, and 1, 3, and 6 months after treatment. RESULTS Of the 31 patients with a baseline AIS grade of A, 2 (6.5%) patients improved to grade B, 5 (16.1%) improved to grade C, and 2 (6.5%) improved to grade D by the 6-month follow-up. The 22 (71.0%) patients who remained at AIS grade A 1 month after injury showed no neurological improvement at the 6-month follow-up. Of the 31 patients with a baseline AIS grade of B, 12 (38.7%) patients showed at least a 1-grade improvement at the 1-month follow-up; 11 (35.5%) patients improved to grade C and 16 (51.6%) patients improved to grade D at the 6-month follow-up. CONCLUSIONS Even in patients with complete motor paralysis caused by cervical SCI without bone and disc injury within 72 hours after trauma, approximately 30% of the patients with an AIS grade of A and 85% of the patients with an AIS grade B improved neurologically after conservative treatment. It is very important to recognize the extent of neurological improvement possible with conservative treatment, even for severe complete motor paralysis.

Puncture of a disc and application of nucleus pulposus induces disc herniation-like changes and osteophytes. An experimental study in rats.

It has been observed that puncture of a lumbar disc may induce formation of a nodule on the surface of the disc and osteophytes. It is not known if this is based on the presence of a foreign tissue or specifically by the presence of nucleus pulposus or on the disc injury. In this study these mechanisms were separated by comparing disc puncture with application of nucleus pulposus without disc injury, with superficial disc injury without nucleus pulposus and with application of fat. Fifty rats underwent facetectomy of the left L4-5 facet. Ten additional rats were used as donor rats. The rats were exposed to disc puncture (n=10), application of homologous nucleus pulposus (n=10), application of homologous fat tissue (n=10), superficial disc injury (n=10) and ten rats served as control. After 3 weeks the rats were examined macroscopically regarding presence of disc nodules and osteophytes. A limited histological analysis was performed to obtain a microscopic overview of any observed changes. In rats with application of fat, superficial disc injury and in sham controls there were almost no changes observed. However, in rats with disc puncture and applied nucleus pulposus there were clear disc nodules and osteophytes noted. Microscopically the nodules comprised granulation tissue and the osteophytes cortical bone. In conclusion, the data indicate that the presence of nucleus pulposus is more likely to be responsible for the formation of disc nodules and osteophytes than disc injury or the presence of a foreign tissue. This may provide new insights in the mechanisms regarding the formation of disc herniations and osteophytes.