3D Bioprinting for Spinal Cord Injury Repair.

Spinal cord injury (SCI) is considered to be one of the most challenging central nervous system injuries. The poor regeneration of nerve cells and the formation of scar tissue after injury make it difficult to recover the function of the nervous system. With the development of tissue engineering, three-dimensional (3D) bioprinting has attracted extensive attention because it can accurately print complex structures. At the same time, the technology of blending and printing cells and related cytokines has gradually been matured. Using this technology, complex biological scaffolds with accurate cell localization can be manufactured. Therefore, this technology has a certain potential in the repair of the nervous system, especially the spinal cord. So far, this review focuses on the progress of tissue engineering of the spinal cord, landmark 3D bioprinting methods, and landmark 3D bioprinting applications of the spinal cord in recent years.

Transforaminal endoscopic excision of bi-segmental non-communicating spinal extradural arachnoid cysts: A case report and literature review.

BACKGROUND: Spinal extradural arachnoid cysts (SEACs) are a rare cause of spinal cord compression. Typically, these cysts communicate with the intradural subarachnoid space through a small defect in the dural sac. For symptomatic SEACs, the standard treatment is to remove the cyst in total with a (hemi)laminectomy or laminoplasty. We present a rare case of bi-segmental non-communicating SEACs and describe our experience of using an endoscopic minimal access technique to remove bi-segmental non-communicating SEACs. CASE SUMMARY: A 79-year-old female presented with pain related to bi-segmental SEACs at the T11-L1 segments. She underwent sequential transforaminal percutaneous endoscopic thoracic cystectomy of the SEACs. Following her first procedure, spinal magnetic resonance imaging demonstrated complete excision of the cyst at the T12-L1 segment. However, the cyst at the T11-T12 segment was still present. Thus, a second procedure was performed to remove this lesion. The patient's right-sided lumbar and abdominal pain improved significantly postoperatively. Her Japanese Orthopaedic Association score increased from 11 to 25, her visual analogue scale score was reduced from 8 to 1. The physical and mental component summary of the 36-item short-form health survey (SF-36) were 15.5 and 34.375 preoperatively, and had increased to 79.75 and 77.275 at the last follow-up visit, respectively. CONCLUSION: Bi-segmental non-communicating SEACs are extremely rare. Endoscopic surgery is a safe, effective, and reliable method for treating these cysts. In the event of bi-segmental SEACs, it is important to identify whether both cysts are communicating before surgery, and if not, to remove both cysts separately during the index surgery to avoid re-operation.

Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion under intraoperative neuromonitoring: A case report.

INTRODUCTION: Traditional open discectomy and intervertebral fusion surgery is the common strategy for lumbar disc herniation (LDH). However, it has the disadvantages of long recovery time and severe paravertebral soft tissue injury. Zina percutaneous screw fixation combined with endoscopic lumbar intervertebral fusion (ZELIF), as a novel minimally invasive surgical technique for LDH, has the advantages in quicker recovery, less soft tissue destruction, shorter hospital stays and less pain. We report a novel technique of ZELIF under intraoperative neuromonitoring (INM) for the treatment of LDH. PATIENT CONCERNS: A 51-year-old male presented to our hospital with left lower extremity pain and numbness for 1 year. DIAGNOSIS: Lumbar disc herniation (LDH). INTERVENTIONS: This patient was treated with Zina percutaneous screw fixation combined with endoscopic neural decompression, endplate preparation, and intervertebral fusion through Kambin's triangle. Each step of the operation was performed under INM. OUTCOMES: The follow-up period lasted 12 months; the hospitalization lasted 4 nights; the blood loss volume was 65 ml, and the time of operation was 266 min. INM showed no neurological damage during the surgery. No surgical complications, including neurological deterioration, cage migration, non-union, instrumentation failure or revision operation, were observed during the follow-up period. Visual Analogue Scale (VAS) score reduced from 7 to 1; the Oswestry Disability Index (ODI) decreased from 43 to 14; the EQ-5D score was 10 preoperatively and 15 at the final follow-up visit; the Physical Component Summary of the 36-Item Short Form Health Survey (SF-36) was 48 preoperatively and 49 at the last follow up visit; the SF-36 Mental Component Summary was 47 before surgery and decreased to 41 postoperatively. CONCLUSION: ZELIF under INM may represent a feasible, safe and effective alternative to endoscopic intervertebral fusion and percutaneous screw fixation, for decompressing the lumbar's exiting nerve root directly with minimal invasion in selected patients.

Neurological deterioration as a result of improper neck position detected by intraoperative neurophysiological monitoring in a cervical stenosis patient: A case report.

RATIONALE: Intraoperative neurophysiological monitoring (IONM) is widely used in spinal surgeries to prevent iatrogenic spinal cord injury (SCI). Most surgeons focus on avoiding neurological compromise intraoperatively, while ignoring the possibility of nerve damage preoperatively, such as neck positioning. Thus, this study aims to report a case with transient neurological deterioration due to improper neck position detected by IONM during cervical surgery. PATIENT CONCERNS: A 63-year-old male patient had been suffering from hypoesthesia of the upper and lower extremities for three years. DIAGNOSES: Severe cervical stenosis (C5-C7) and cervical ossification of a posterior longitudinal ligament. INTERVENTIONS: The cervical stenosis patient underwent an anterior cervical corpectomy decompression and fusion (ACDF) surgery with the assistance of IONM. When the lesion segment was exposed, the SSEP and MEP suddenly elicited difficulty indicating that the patient may have developed SCI. All the technical causes of IONM events were eliminated, and the surgeon suspended operation immediately and suspected that the IONM alerts were caused by cervical SCI due to the improper position of the neck. Subsequently, the surgeon repositioned the neck of the patient by using a thinner shoulders pad. OUTCOMES: At the end of the operation, the MEP and SSEP signals gradually returned to 75% and 80% of the baseline, respectively. Postoperatively, the muscle strength of bilateral biceps decreased from grade IV to grade III. Besides, the sensory disturbance of both upper extremities aggravated. However, the muscle power and hypoesthesia were significantly improved after three months of neurotrophic therapy and rehabilitation training, and no complications of nerve injury were found at the last follow-up visit. LESSONS: IONM, consisting of SSEP and MEP, should be applied throughout ACDF surgery from the neck positioning to suture incisions. Besides, in the ward 1to 2 days before operation, it is necessary for conscious patients with severe cervical stenosis to simulate the intraoperative neck position. If the conscious patients present signs of nerve damage, they can adjust the neck position immediately until the neurological symptoms relieve. Therefore, intraoperatively, the unconscious patient can be placed in a neck position that was confirmed preoperatively to prevent SCI.

Comparative evaluation of posterior percutaneous endoscopy cervical discectomy using a 3.7 mm endoscope and a 6.9 mm endoscope for cervical disc herniation: a retrospective comparative cohort study.

BACKGROUND: Posterior percutaneous endoscopy cervical discectomy (p-PECD) is an effective strategy for the treatment of cervical diseases, with a working cannula ranging from 3.7 mm to 6.9 mm in diameter. However, to date, no studies have been performed to compare the clinical outcomes of the use of endoscopes with different diameters in cervical disc herniation (CDH) patients. The purpose of this study was to compare the clinical outcomes of patients with unilateral CDH treated with p-PECD using a 3.7 mm endoscope and a 6.9 mm endoscope. METHODS: From January 2016 to June 2018, a total of 28 consecutive patients with single-level CDH who received p-PECD using either the 3.7 mm or the 6.9 mm endoscope were enrolled. The clinical results, including the surgical duration, hospitalization, visual analog scale (VAS) score and modified MacNab criteria, were evaluated. Cervical fluoroscopy, CT, and MRI were also performed during follow-up. RESULTS: Tthere was a significant difference in regard to the average identification time of the "V" point (18.608 ± 3.7607 min vs. 11.256 ± 2.7161 min, p < 0.001) and the mean removal time of the overlying tissue (16.650 ± 4.1730 min vs. 12.712 ± 3.3079 min, p < 0.05) for the use of the 3.7 mm endoscope and the 6.9 mm endoscope, respectively. The postoperative VAS and MacNab scores of the two endoscopes were significantly improved compared with those the preoperative scores (p < 0.05). CONCLUSION: The application of both the 3.7 mm endoscope and 6.9 mm endoscope represent an effective method for the treatment of CDH in selected patients, and no significant difference can be observed in the clinical outcomes of the endoscopes. The 6.9 mm endoscope shows superiority to the 3.7 mm endoscope in terms of the efficiency of "V" point identification, the removal of overlying soft tissue and the prevention of spinal cord injury. However, the 6.9 mm endoscope may be inferior to the 3.7 mm endoscope in regards to anterior foraminal decompression due to its large diameter; this result needs to be further evaluated with the support of a large number of randomized controlled trials.

Selective nerve root block combined with posterior percutaneous cervical endoscopic discectomy for cervical spondylotic radiculopathy with double nerve root variation: A case report.

RATIONALE: The aim of this report is to present the technique of selective nerve root blockage combined with posterior percutaneous cervical endoscopic discectomy (PPECD) for cervical spondylotic radiculopathy (CSR). PATIENT CONCERNS: A 49-year-old female has pain in the skin area of the left scapular, pain in left elbow and limitation of left upper limb movement for 1.5 years. DIAGNOSIS: She was diagnosed with CSR and C6-7 double nerve root variation. INTERVENTIONS: We used selective nerve root block to determine the lesion segment and applied PPECD to relieve pressure on the patient's nerve roots. OUTCOMES: The pain symptoms disappeared after the patient was treated with C6-7 nerve root block. Endoscopic displayed C6-7 double nerve root variation on the left side of the spinal cord intraoperative. The neurological function was intact postoperatively and no recurrence of cervical disc herniation during the 5 months' follow-up period. The hospitalization time was 5 days, the operation time was 68.2 minutes and the bleeding volume was 52.6 ml. There was no change in cervical curvature and cervical disc height postoperatively. Japanese Orthopaedic Association score, SF-36 score and Visual Analogue Scale score improved significantly postoperatively. LESSONS: The application of selective nerve root blockage combined with PPECD for CSR could achieve satisfactory effect of position and decompression of the injured nerve root. Besides, we recommend that surgery be performed under general anesthesia to minimize patients' emotional stress and discomfort.

Comparison of one-level microendoscopy laminoforaminotomy and cervical arthroplasty in cervical spondylotic radiculopathy: a minimum 2-year follow-up study.

BACKGROUND: This study aims to compare the perioperative parameters and clinical results between microendoscopy laminoforaminotomy (MELF) and cervical arthroplasty (CA) in the treatment of one-level cervical spondylotic radiculopathy in a retrospective study. METHODS: From 2003 to 2007, a total of 97 patients with one-level cervical spondylotic radiculopathy were treated. Forty-five patients underwent CA. Fifty-two patients underwent MELF. Patient demographics and operative data were collected with a minimum 2-year follow-up. Perioperative parameters were compared. Clinical assessment in terms of neck disability index (NDI), short form (SF)-36, and visual analogue scale (VAS) of arm pain and neck pain was performed prior to surgery and at 1.5, 3, 6, 12, and 24 months after surgery. RESULTS: Fluoroscopy time (CA, 60.3 s; MELF, 12.1 s; P < 0.01) and surgical time (CA, 95.1 min; MELF, 24.0 min; P < 0.01) were significantly longer in the CA cases. Shorter hospitalized days (CA, 1.1 days; MELF, 0.13 days; P < 0.01) and less estimated blood loss (EBL; CA, 75.8 ml; MELF, 31.9 ml; P < 0.01) were observed in the MELF group. Both CA and MELF groups showed significant improvement in NDI, VAS of neck pain and arm pain, and SF-36 (P < 0.05 for each) at 1.5, 3, 6, 12, and 24 months after surgery, but there was no significant difference between them (P > 0.05). CONCLUSIONS: As alternatives of anterior cervical decompression and fusion (ACDF), both CA and MELF can produce satisfactory clinical outcomes. MELF has the additional benefits of less blood loss, less surgical time, less X-ray time, and shorter hospital stay.

Role of endoplasmic reticulum stress in aberrant activation of fluoride-treated osteoblasts.

The aberrant activation of osteoblasts in the early stage is one of the critical steps during the pathogenesis of skeletal fluorosis. The endoplasmic reticulum (ER) stresses and unfolded protein response (UPR) are initiated to alleviate the accumulation of unfolded proteins against cell injury. The previous researches had demonstrated that fluoride induced ER stress in other cells or tissues. In this study, we determined the ER stress and UPR to investigate their roles in aberrant activation of fluoride-treated osteoblasts. The gene expression of bone markers and UPR factors in MC3T3-E1 cells treated with varying doses of fluoride administration was analyzed. Meantime, levels of glutathione and glutathione disulfide were tested by the ultraperformance liquid chromatography-tandem mass spectrometry applications. Our results indicated that a certain dose and period of fluoride administration induced cell proliferation and differentiation, and Runx2 was involved in the regulation of osteoblastic differentiation of MC3T3-E1 cells. Increase trend of Runx2 expression was consistent with change of marker of ER stress. Fluoride caused ER stress and stimulated UPR during the process of osteoblast maturation, while oxidative stress was also active in the occurrence of ER stress. These data indicated that ER stress and UPR were possibly involved in the action of fluoride on osteoblasts.

Effect of fluoride on insulin level of rats and insulin receptor expression in the MC3T3-E1 cells.

Studies on the role of insulin and insulin receptor (InsR) in the process of skeletal fluorosis, especially in osteogenic function, are rare. We evaluated the effect of increasing F⁻ doses on the marker of bone formation, serum insulin level and pancreatic secretion changes in vivo and mRNA expression of InsR and osteocalcin (OCN) in vitro. Wistar rats (n = 50) were divided into two groups, i.e. a control group and fluoride group. The fluoride groups were treated with fluoride by drinking tap water containing 100 mg F⁻/L. The fluoride ion-selective electrode measured the fluoride concentrations of femurs. The alkaline phosphatase (ALP), OCN, insulin and glucagon of serum were tested to observe the effect of fluoride action on them. Meantime, the pancreas pathological morphometry analysis via ß cells stained by aldehyde fuchsin showed the action of fluoride on pancreas secretion. MC3T3-E1 cells (derived from newborn mouse calvaria) were exposed to varying concentrations and periods of fluoride. The mRNA expression of InsR and OCN was quantified with real-time PCR. Results showed that 1-year fluoride treatment obviously stimulated ALP activity and OCN level along with increase of bone fluoride concentration of rats, which indicated that fluoride obviously stimulated osteogenic action of rats. In vitro study, the dual effect of fluoride on osteoblast function is shown. On the other hand, there was a significant increase of serum insulin level and a general decrease of glucagon level, and the histomorphometry analysis indicated an elevated insulin-positive area and increase in islet size in rats treated with fluoride for 1 year. In addition, fluoride obviously facilitated the mRNA expression of InsR in vitro. To sum up, there existed a close relationship between insulin secretion and fluoride treatment. The insulin signal pathway might be involved in the underlying occurrence or development of skeletal fluorosis.

Elevation of PTH and PTHrp induced by excessive fluoride in rats on a calcium-deficient diet.

Study on the role of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrp) in the process of skeletal fluorosis, involved especially in calcium deficiency, is rare. We evaluated the level of serum PTH and mRNA expression of PTHrp in femur when rats were exposed to excessive fluoride with low-calcium diet. Wistar rats (n = 60) was divided into four groups, a control group, fluoride group, low-calcium group, and low-calcium fluoride group. The fluoride groups were treated with fluoride by drinking tap water containing 100 mg F-/L. The low-calcium diet contained 0.05% calcium. Serum was collected in the first, fourth, eighth, and 12th of phase for the detemination of PTH and Ca(2+). RNA extraction from femora was used to analyze the mRNA express of PTHrp, osteopontin (OPN), and osteocalcin (OCN) after 12 weeks of fluoride dosing. Results showed that serum PTH increased gradually with the extension of fluoride exposure, but Ca2+ decreased, both of which embodied a time-dependent relationship. Cotreatment of excessive fluoride with low-calcium diet largely stimulated the secretion of PTH. The low dietary calcium markedly increased mRNA expression of PTHrp in animals with fluoride treatment. Expression of OPN and OCN significantly increased in the rats treated with excessive fluoride and low-calcium diet. We demonstrated that fluoride by itself affected the body's calcium metabolism and stimulate the secretion of PTH. PTH may play an important role in anabolic effect of excessive fluoride on bone turnover of skeletal fluorosis and calcium deficiency exacerbated the action of PTH and PTHrp on the characteristic bone lesion of fluorosis.