Non-stem cell-derived exosomes: a novel therapeutics for neurotrauma.

Neurotrauma, encompassing traumatic brain injuries (TBI) and spinal cord injuries (SCI) impacts a significant portion of the global population. While spontaneous recovery post-TBI or SCI is possible, recent advancements in cell-based therapies aim to bolster these natural reparative mechanisms. Emerging research indicates that the beneficial outcomes of such therapies might be largely mediated by exosomes secreted from the administered cells. While stem cells have garnered much attention, exosomes derived from non-stem cells, including neurons, Schwann cells, microglia, and vascular endothelial cells, have shown notable therapeutic potential. These exosomes contribute to angiogenesis, neurogenesis, and axon remodeling, and display anti-inflammatory properties, marking them as promising agents for neurorestorative treatments. This review provides an in-depth exploration of the current methodologies, challenges, and future directions regarding the therapeutic role of non-stem cell-derived exosomes in neurotrauma.

Comparative Effects of Different Epidural Injection Approaches on Lumbosacral Radicular Pain: A Systematic Review and Network Meta-analysis.

BACKGROUND: Lumbar disc herniation (LDH) is the main cause of low back pain and/or radiculopathy. Currently, epidural intervention is a widely used and effective conservative treatment method for managing low back and radicular pain caused by LDH. OBJECTIVES: To explore the effectiveness of different epidural injection approaches in adult patients with lumbosacral radicular pain. STUDY DESIGN: Systematic review and network meta-analysis (NMA). METHODS: An electronic literature search was performed in the Pubmed, Embase, Cochrane Library, and Web of Science databases. Two authors independently performed data extraction and quality assessment. A Bayesian random effects model was conducted to incorporate the estimates of direct and indirect treatment comparisons and rank the interventions in order. Effect estimates from Bayesian NMA were presented as mean difference (MD) with 95% credible intervals (CrI). RESULTS: This NMA assessed caudal (C), interlaminar (IL), transforaminal (TF) and parasagittal interlaminar (PIL) epidural injection approaches for lumbosacral radicular pain from 7 trials. A statistically significant treatment difference for pain relief was reported for midline interlaminar (MIL) vs PIL (MD, 1.16; 95%CrI, 0.31-2.06), MIL vs TF (MD, 1.12; 95%CrI, 0.51-1.85), C vs TF (MD, 1.07; 95%CrI, 0.01-2.18) in short-term follow-up and MIL vs TF (MD, 1.8; 95% CrI, 0.3-3.48) in intermediate-term follow-up. For functional improvement, a statistically significant difference was observed with MIL vs PIL (MD, 9.9; 95% CrI, 0.64-19.94) and MIL vs TF (MD, 1.08; 95% CrI, 1.08-17.08) in short-term follow-up. Moreover, the PIL approach and TF appeoach were ranked in the top 2 for pain relief and functional improvement, both in short-term and intermediate-term follow-up. LIMITATIONS: 1) The number of studies included was small; 2) some treatments lacked direct comparisons; 3) only scores from the visual analog scale for pain and the Oswestry Disability Index were included in the result; 4) important outcomes, such as complications, were not included. CONCLUSION: In short-term and intermediate-term follow-up, the PIL approach has the highest probability for pain relief and functional improvement.

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.

Corrigendum: Comparative Analysis of the Biomechanics Characteristics After Different Minimally Invasive Surgeries for Cervical Spondylopathy: A Finite Element Analysis.

[This corrects the article DOI: 10.3389/fbioe.2021.772853.].

Osteogenic effect of polymethyl methacrylate bone cement with surface modification of lactoferrin.

Polymethyl methacrylate (PMMA) bone cement is a commonly used filling material in orthopedic surgery. Its good and stable performances make it the most widely used in all kinds of bone cement. With the advancement of the application and research of PMMA bone cement by surgeons, its disadvantages such as non-degradation and non-bioactivity are gradually exposed. In recent years, the biological functions of lactoferrin (LF) have been gradually explored, especially its role in promoting osteogenesis. In this study, LF was modified on the surface of solidified PMMA bone cement (LF/PMMA bone cement) by physical/chemical mixed modification and verified by cytological experiments in vitro. In vitro studies have implicated that PMMA bone cement modified with LF can improve the attachment, expansion, proliferation, extracellular matrix secretion and osteogenic differentiation of mouse preosteoblasts (MC3T3-E1) cells, indicating biocompatibility. This experiment provides a novel insight for improving the biological activity of PMMA bone cement and lays a foundation for broadening the clinical application of PMMA bone cement.

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.

Comparative Analysis of the Biomechanical Characteristics After Different Minimally Invasive Surgeries for Cervical Spondylopathy: A Finite Element Analysis.

Minimally invasive surgeries, including posterior endoscopic cervical foraminotomy (PECF), microsurgical anterior cervical foraminotomy (MACF), anterior transdiscal approach of endoscopic cervical discectomy (ATd-ECD), and anterior transcorporeal approach of endoscopic cervical discectomy (ATc-ECD), have obtained positive results for cervical spondylotic radiculopathy. Nonetheless, there is a lack of comparison among them regarding their biomechanical performance. The purpose of this study is to investigate the biomechanical changes of operated and adjacent segments after minimally invasive surgeries compared to a normal cervical spine. A three-dimensional model of normal cervical vertebrae C3-C7 was established using finite element analysis. Afterwards, four surgical models (PECF, MACF, ATd-ECD, and ATc-ECD) were constructed on the basis of the normal model. Identical load conditions were applied to simulate flexion, extension, lateral bending, and axial rotation of the cervical spine. We calculated the range of motion (ROM), intradiscal pressure (IDP), annulus fibrosus pressure (AFP), uncovertebral joints contact pressure (CPRESS), and facet joints CPRESS under different motions. For all circumstances, ATc-ECD was close to the normal cervical spine model, whereas ATd-ECD significantly increased ROM and joints CPRESS and decreased IDP in the operated segment. PECF increased more the operated segment ROM than did the MACF, but the MACF obtained maximum IDP and AFP. Except for ATc-ECD, the other models increased joints CPRESS of the operated segment. For adjacent segments, ROM, IDP, and joints CPRESS showed a downward trend in all models. All models showed good biomechanical stability. With their combination biomechanics, safety, and conditions of application, PECF and ATc-ECD could be appropriate choices for cervical spondylotic radiculopathy.

Occipitocervical fusion combined with 3-dimensional navigation and 3-dimensional printing technology for the treatment of atlantoaxial dislocation with basilar invagination: A case report.

INTRODUCTION: Basilar invagination (BI) is a common deformity in the occipitocervical region. The traditional surgical method of BI is direct transoral decompression followed by posterior decompression and fixation. Posterior-only decompression and fixation have achieved good efficacy in the treatment of BI in recent years, but complications are common due to the operation in the upper cervical vertebra and the medulla oblongata region. Moreover, posterior-only occipitocervical fusion combined with an intraoperative 3-dimensional (3D) navigation system is relatively rare, and reports of this procedure combined with 3D printing technology have not been published. We present a case of BI treated with posterior-only occipitocervical fusion combined with 3D printing technology and 3D navigation system to reduce the risk of surgical complications. PATIENT CONCERNS: A 55-year-old patient with a history of neck pain and numbness of the extremities for 6 years developed a walking disorder for 1 year. DIAGNOSES: Atlantoaxial dislocation with BI. INTERVENTIONS: The patient underwent posterior-only occipitocervical fusion combined with intraoperative 3D navigation system and 3D printing technology. OUTCOMES: The patient's walking disorder was resolved and he was able to walk approximately 100 m by himself when he was allowed to get up and move around with the help of a neck brace. At 6 months postoperatively, the patient reported that the numbness of the limbs was reduced, and he could walk >500 m by himself. CONCLUSION: Occipitocervical fusion is one of the established techniques for the treatment of BI. The biggest advantage of the 2 technologies was that it ensured precise implant placement. The advantages of intraoperative 3D navigation systems are as follows: real-time intraoperative monitoring of the angle and depth of implant placement; the best nailing point can be determined at the time of implantation, rather than according to the operator's previous experience; and the extent of screw insertion is visible to the naked eye, rather than being dependent on the "hand feel" of the surgeon. At the same time, the 3D printing technology can be applied to clarify the relationship between blood vessels and bone around the implant to minimize injury to important structures during implantation.

Cauda equina syndrome without motor dysfunction following lumbar spinal stenosis surgery: A case report.

RATIONALE: Cauda equina syndrome (CES) refers to a group of symptoms that occur when the nerves in the cauda equina become compressed or damaged. The most common etiology of CES is lumbar intervertebral disc herniation, but CES following lumbar spinal surgery is rare, especially without motor dysfunction. Herein, we illustrate a case of CES that developed as a complication of spinal surgery and to deduce its possible underlying cause. PATIENT CONCERNS: A 46-year-old man experienced lumbago, bilateral shank pain, and numbness with neurogenic claudication for 3 years due to degenerative lumbar disc herniation and spinal cord stenosis. After a thorough examination to diagnose lumbar spinal stenosis, the patient underwent bilateral decompression and pedicle screw system internal fixation with bone graft. Postoperatively, the patient showed regained strength in his bilateral shanks, and he did not complain of lumbago and shank pain, but CES occurred, which manifested as underpants-type numbness in the perineum without bladder, anal, and motor dysfunction. DIAGNOSES: CES as a postoperative complication of lumbar stenosis. INTERVENTIONS: The patient underwent bilateral laminectomies, partial facetectomies, and pedicle screw system internal fixation and fusion with bone graft. Postoperatively, the patient performed adequate rehabilitation exercises and was expected to recover spontaneously. OUTCOMES: The symptoms of pain and claudication resolved after 3 weeks in the hospital, but an underpants-type hypoesthesia in the perineum without motor dysfunction developed. The patient experienced full recovery from CES 6 months after surgery. LESSONS: CES as a complication of lumbar spinal surgery is very rare. Excessive sensitivity to the traction of the dural sac was, in our opinion, the most possible cause of postoperative CES in this case. When the nerve root is pulled intraoperatively, it is best not to cross the central line of the spinous process. The plane of the nerve retractor needs to be parallel to the dural sac at the pulling point to reduce the formation of shear force. Most importantly, gentle maneuver is required because sensitivity to the traction of the dural sac varies individually.