Abnormal types of intervertebral disc structure and related mechanical loading with biomechanical factors / 中国组织工程研究

BACKGROUND:The problem of intervertebral disc injury and degeneration has been studied in many ways.Many studies have shown that intervertebral disc injury and degeneration is driven by mechanical loading factors.However,the potential relationship between common phenotypes of intervertebral disc injury and degeneration and mechanical loading factors has been rarely summarized. OBJECTIVE:To summarize the types of common structural abnormalities exhibited by intervertebral disc injury and degeneration in the published literature,and sum up the potential links to the types of mechanical loading that lead to these structural abnormalities in in vitro and ex vivo experimental studies. METHODS:Using the terms"intervertebral disc failure,intervertebral disc injury,mechanical load,mechanical factor,load factor,biomechanics"as Chinese and English key words in PubMed,CNKI,and WanFang databases,articles related to intervertebral disc injury degeneration and mechanical load factors were retrieved.Literature screening was performed according to the inclusion and exclusion criteria,and 88 articles were finally included. RESULTS AND CONCLUSION:(1)Common structural abnormalities of intervertebral discs include decreased intervertebral disc height,disc bulge,osteophyte formation,annulus fibrosus tear,intervertebral disc herniation or disc prolapse,endplate damage,Schmorl nodes and intervertebral disc calcification.Intervertebral discs are susceptible to mechanical load types such as compression,bending,axial rotation,and compound loads.(2)The compressive load mainly causes the decrease of the proteoglycan content and the water-binding ability of the intervertebral disc,leading to the decrease or swelling of the intervertebral disc and further damage and degeneration of the intervertebral disc.In addition,the excessive compressive load causes greater damage to the endplate.(3)Bending load and axial rotation load damage the annulus fibrosus more than the endplate,and prolonged or repeated bending loads can cause tearing of the fibrous annulus and herniation or prolapse of the intervertebral disc,while pure axial rotation loads can induce less damage to the intervertebral disc and only cause the tear of the annulus fibrosus.(4)However,when different load types act in combination,it is more likely to result in high stress on the disc and a greater risk of disc injury.(5)Injury and degeneration of the intervertebral disc present progressive structural damage,and early prevention and protection are particularly important in clinical practice.Future tissue engineering research can start with early repair of the intervertebral disc.

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.

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.

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.

Application of modified minimally invasive lateral interbody fusion in anterior support and reconstruction for thoracolumbar fracture combined with intervertebral disc injury / 中华创伤杂志

Objective To investigate the preliminary clinical efficacy of modified minimally invasive lateral interbody fusion in the anterior support and reconstruction for thoracolumbar fracture combined with intervertebral disc injury. Methods A retrospective case series study was conducted to analyze the clinical data of 14 patients with single-segment thoracolumbar fracture combined with intervertebral disc injury admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine from December 2017 to May 2018. There were 12 males and two females, aged 22-56 years [(37. 4 ± 10. 2)years]. The injured segments were at L1 in nine patients and L2 in five patients. Twelve patients had upper disc injury and two patients had lower disc injury. Before operation, American Spinal Injury Association ( ASIA) classification was grade A in five patients, grade B in four, grade C in three, and grade D in two. All patients received modified minimally invasive lateral interbody fusion to reconstruct the stability of the anterior and middle columns of the spine one week after posterior short-segment fixation. The operation time, intraoperative bleeding, postoperative hospital stay and complications were recorded. Pain visual analogue scale ( VAS) and ASIA nerve injury grading were used to evaluate the clinical efficacy. The Cobb angle changes of the operative segment and lumbar lordosis were compared before operation and during the last follow-up. Results The patients were followed up for 6-14 months[(12.1 ±3.6)months]. The operation time was 65-210 minutes [(138.9 ±39.4)minutes],and the intraoperative blood loss was 250-600 ml [(407. 1 ± 119. 1) ml], respectively. The total postoperative length of stay ranged from 3 to 13 days [(7. 8 ± 2. 5)days]. The incisions healed well at stage I in all patients. VAS for back pain and leg pain before operation were (6. 3 ± 2 . 4)points and (4. 1 ± 1. 3) points respectively. The final VAS for back pain and leg pain were (2. 2 ± 0. 6)points and (2. 3 ± 0. 8)points, which were significantly lower than the preoperative VAS (both P<0. 01). At the last follow-up, there was one patient with grade A, two with grade B, five with grade C, one with grade D, and five with grade E. Postoperative CT showed that decompression was complete, implants were in good position and internal fixation was reliable. Preoperative Cobb angles of lumbar lordosis and the injury segment were ( -7. 8 ± 3. 9)° and (24. 8 ± 6. 9)° respectively. The final Cobb angles of lumbar lordosis and the injury segment were (3. 1 ± 2. 7)° and (30. 7 ± 9. 6)°, which were significantly restored compared with preoperative values (both P<0. 01). One patient had postoperative pain in the front thigh, and another patient had numbness in the front thigh, whose symptoms were alleviated after non-surgical treatment. No serious surgical complications such as quadriceps femoris and weakness, pleural tear, vascular injury, nerve root injury, sympathetic nerve injury, retroperitoneal hematoma and artificial vertebral body displacement occurred in these patients. Conclusions For anterior reconstruction of the thoracolumbar fracture with intervertebral disc injury, the modified minimally invasive lateral interbody fusion has the advantages of less invasive, less blood loss, shorter hospitalization time, low incidence of complications. Significant pain relief, neurological function improvement, and anterior and middle column reconstruction can be achieved postoperatively.

Application of modified minimally invasive lateral interbody fusion in anterior support and reconstruction for thoracolumbar fracture combined with intervertebral disc injury / 中华创伤杂志

Objective@#To investigate the preliminary clinical efficacy of modified minimally invasive lateral interbody fusion in the anterior support and reconstruction for thoracolumbar fracture combined with intervertebral disc injury.@*Methods@#A retrospective case series study was conducted to analyze the clinical data of 14 patients with single-segment thoracolumbar fracture combined with intervertebral disc injury admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine from December 2017 to May 2018. There were 12 males and two females, aged 22-56 years [(37.4±10.2)years]. The injured segments were at L1 in nine patients and L2 in five patients. Twelve patients had upper disc injury and two patients had lower disc injury. Before operation, American Spinal Injury Association (ASIA) classification was grade A in five patients, grade B in four, grade C in three, and grade D in two. All patients received modified minimally invasive lateral interbody fusion to reconstruct the stability of the anterior and middle columns of the spine one week after posterior short-segment fixation. The operation time, intraoperative bleeding, postoperative hospital stay and complications were recorded. Pain visual analogue scale (VAS) and ASIA nerve injury grading were used to evaluate the clinical efficacy. The Cobb angle changes of the operative segment and lumbar lordosis were compared before operation and during the last follow-up.@*Results@#The patients were followed up for 6-14 months[(12.1±3.6)months]. The operation time was 65-210 minutes [(138.9±39.4)minutes], and the intraoperative blood loss was 250-600 ml [(407.1±119.1)ml], respectively. The total postoperative length of stay ranged from 3 to 13 days [(7.8±2.5)days]. The incisions healed well at stage I in all patients. VAS for back pain and leg pain before operation were (6.3±2 .4)points and (4.1±1.3)points respectively. The final VAS for back pain and leg pain were (2.2±0.6)points and (2.3±0.8)points, which were significantly lower than the preoperative VAS (both P<0.01). At the last follow-up, there was one patient with grade A, two with grade B, five with grade C, one with grade D, and five with grade E. Postoperative CT showed that decompression was complete, implants were in good position and internal fixation was reliable. Preoperative Cobb angles of lumbar lordosis and the injury segment were (-7.8±3.9)° and (24.8±6.9)° respectively. The final Cobb angles of lumbar lordosis and the injury segment were (3.1±2.7)° and (30.7±9.6)°, which were significantly restored compared with preoperative values (both P<0.01). One patient had postoperative pain in the front thigh, and another patient had numbness in the front thigh, whose symptoms were alleviated after non-surgical treatment. No serious surgical complications such as quadriceps femoris and weakness, pleural tear, vascular injury, nerve root injury, sympathetic nerve injury, retroperitoneal hematoma and artificial vertebral body displacement occurred in these patients.@*Conclusions@#For anterior reconstruction of the thoracolumbar fracture with intervertebral disc injury, the modified minimally invasive lateral interbody fusion has the advantages of less invasive, less blood loss, shorter hospitalization time, low incidence of complications. Significant pain relief, neurological function improvement, and anterior and middle column reconstruction can be achieved postoperatively.

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.

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.

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.