Difficulty Obtaining Daily Necessities and Difficulty Obtaining SCI Services During the COVID-19 Pandemic Among People With Spinal Cord Injury.

OBJECTIVE: To describe the self-reported difficulties during the COVID-19 pandemic on the lives of persons with traumatic spinal cord injury (SCI), and to identify the factors measured prior the pandemic that predict the number of difficulties obtaining daily necessities and difficulties obtaining SCI services during the pandemic. DESIGN: Cohort study. SETTING: A state SCI outcomes follow-up database in the southeastern United States. PARTICIPANTS: 297 participants (N=297) met the following eligibility criteria: (1) ≥18 years of age, (2) traumatic SCI, (3) minimum of 1-year post-injury, and (4) having completed a longitudinal study questionnaire immediately prior to the pandemic (between 12/1/2019 and 03/11/2020). INTERVENTIONS: N/A. MAIN OUTCOME MEASURE(S): The outcome measures were the self-reported number of difficulties obtaining daily necessities (difficulties to get food, medication, and routine medical/dental care) and difficulties obtaining SCI services during the pandemic (difficulties to get treatment for SCI-related problems, to maintain regular SCI equipment, and to get SCI supplies). RESULTS: Among 297 eligible participants, 247 (83%) have completed the follow-up during the pandemic between December 2020 and December 2021. There were 22% participants having at least 1 difficulty obtaining daily necessities and 19% participants having at least 1 difficulty obtaining SCI services. Younger, ambulatory participants, cervical 1-4 injury level, lower household income, more health conditions, and no routine health care access prior to the pandemic were associated with greater number of difficulties obtaining daily necessities. Women, non-ambulatory participants, marital relation, having need for physical assistance, more health conditions, and no routine health care access prior to the pandemic related to greater number of difficulties obtaining SCI services. CONCLUSIONS: People with SCI have experienced living difficulties during the COVID-19 pandemic. Of particular importance, no routine health care access and more health conditions are related to more difficulties obtaining both daily necessities and SCI services after controlling the socio-demographics and injury characteristics.

Hydrophilic catheters for intermittent catheterization and occurrence of urinary tract infections. A retrospective comparative study in patients with spinal cord Injury.

BACKGROUND: Neurogenic bladder dysfunction is a major problem for spinal cord injury (SCI) patients not only due to the risk of serious complications but also because of the impact on quality of life. The main aim of this study is to compare the rate of urinary tract infection (UTI) associated with hydrophilic-coated catheters versus uncoated polyvinyl chloride (PVC) catheters among SCI patients presenting with functional neurogenic bladder sphincter disorders. METHODOLOGY: This was a retrospective cohort study from 2005 to 2020 including adult male or female patients who have an SCI at least more than 1 month ago with neurogenic bladder dysfunction and were using intermittent catheterization (single-use hydrophilic-coated or the standard-of-care polyvinyl chloride uncoated standard catheters) at least 3 times a day to maintain bladder emptying. RESULTS: A total of 1000 patients were selected and recruited through a stratified random sampling technique with 467 (47.60%) patients in the uncoated catheter arm and 524 (52.60%) in the coated catheter groups. The three outcome measures, namely: symptomatic UTI, Bacteriuria, and pyuria were significantly higher in the group using uncoated polyvinyl chloride (PVC) catheters compared to hydrophilic-coated catheters at the rate of 79.60% vs.46.60%, 81.10% vs. 64.69, and 53.57% versus 41.79% respectively. Males, elder patients, longer duration, and severity of SCI were associated with increased risk of symptomatic UTI. CONCLUSIONS: The results indicate a beneficial effect regarding clinical UTI when using hydrophilic-coated catheters in terms of fewer cases of symptomatic UTI. Bacteriuria is inevitable in patients with long-term catheterization, however, treatment should not be started unless the clinical symptoms exist. More attention should be given to the high-risk group for symptomatic UTIs.

Database Review of 514 Patients with Os Odontoideum. Detailed Analysis of 258 Surgically Treated (1978-2019).

OBJECTIVE: Database review (1978-2019) is to identify the cause of os odontoideum, its presentation, associated abnormalities, and management recommendations. METHODS AND MATERIALS: Review of referral database of 514 patients and 258 surgically treated patients ages 4-64 years. Detailed history of early childhood trauma and initial encounter record retrieval were made. Patients had dynamic motion radiographs, dynamic motion MRI and also CT to identify pathology and reducibility of craniocervical instability. Preoperative crown halo traction was made before the year 2000 except in children. Intraoperative traction with O-arm/CT documentation was made since 2001. Reducible and partially reducible cases underwent halo traction under general anesthesia distraction, dorsal stabilization, and rib graft augmentation for fusion. Later semi-rigid instrumentation and subsequently rigid instrumentation was made. Irreducible compression of cervicomedullary junction was treated with ventral decompression. The follow up was 3-20 years. RESULTS: Database; acute worsening after trauma 262, insidious neurological deficit 252. Minimal/normal motion with neurological deficit was present in 18, previous C1-C2 fusion with worsening in 18. 28 patients of 64 without treatment worsened in 4 years. An intact odontoid process was seen in 52 children of 156 who had early craniovertebral junction trauma and later developed os odontoideum. SURGICAL EXPERIENCE: There were 174 patients with reducible lesions and partially reducible were 22. Irreducible lesions were 62. Of the reducible, 50 underwent transarticular C1-C2 fusion, 26 C1 lateral mass, and C2 pars screw fixation. 182 had occipitocervical fusion (19 had extension of previous C1-C2 fusion and 43 after transoral decompression). 62 with irreducible ventral compression of the cervicomedullary junction underwent transoral decompression; 43 had a trapped transverse ligament between the os and C2 body and 19 previous C1-C2 fusions. Compression was by the axis body, os odontoideum, and the posterior C2 arch. Syndromic and skeletal/connective tissue abnormalities were found in 86 (36%). COMPLICATIONS: 2 patients worsened, age 10 and 62, due to failure of semi-rigid construct. CONCLUSIONS: The etiology of os odontoideum is multifactorial considering the associated abnormalities, reports of congenital-familiar occurrence, and early childhood craniovertebral trauma which also plays a role in the etiology. Patients with reducible lesions require stabilization. Asymptomatic patients are at risk for later instability. Patients who underwent childhood C1-C2 fusion must be followed for later problems. The irreducibility was seen due to trapped transverse ligament, pannus, or previous dorsal C1-C2 fusion.

Epidemiology of pediatric spinal trauma with neurological deficits in Catalonia: a 36-year experience.

PURPOSE: Existing literature on pediatric traumatic spinal cord injury (PTSCI) demonstrates large variations in characteristics, incidence, time-periods and etiology, worldwide. Epidemiological studies addressing injuries to the total spine, conducted in Southern European regions are remarkably scarce; therefore we aimed to investigate long-term trends analyzing etiology, fracture location and type, single or multiple fractures, associated lesions and neurological status in Catalonia, Spain. METHODS: We conducted a retrospective observational study. We analyzed post-acute patients after PTSCI, aged 0-17, admitted with neurological deficits between 1986 and 2022 to a specialized hospital in Catalonia. Neurological deficits were assessed using the American Spinal Injury Association Impairment Scale (AIS). RESULTS: Two hundred and forty nine children were included, 174 (69.9%) boys and 75 (30.1%) girls; mean age was 13.9 years (range, 2 months to 17 years). Two hundred and four children (82%) had ≥ 1 spinal fractures, 66 (26.5%) dislocations and 8 (3.2%) SCIWORA. Fractures were multilevel contiguous in 108 (43.4%) cases. Fracture types comprised 81 vertebral compactions (32.5%), 22 burst fractures (8.8%), 7 odontoid (2.8%) and 4 tear-drops (1.6%). There were ≥ 1 associated lesions in 112 cases (45%): in limbs in 23 cases (9.2%), thorax or abdomen in 59 (23.7%) and skull or face in 81 (32.5%). In 44 cases (39% of the 112) there were multiple lesions. Locations comprised cervical spine in 105 cases (42%), thoracic spine in 124 (49%), lumbar spine in 18 (7%), and sacrum in 2 (0.8%). Road traffic accidents (RTAs) were the main etiology (62.2%) over the whole period. However, from 2016 onwards, RTAs dropped below the rate of falls and sports injuries. The most common sites for injury in those aged 9 years or older were in the cervical (41.1%) and thoracic (50.7%) regions. Those aged 8 or under were far more likely to sustain a complete SCI (80.0%) or an accompanying traumatic brain injury (45.0%) likely due to higher numbers of pedestrian versus car RTAs. A significant peak in the occurrence of cases during 2006-2010 (20.1%) was identified with an absolute drop immediately after, during 2011-2015 (8.8%). A marked shift in trend is observed between 2016-2022 regarding age of injuries (an increase in 9 years or older), etiology (increase in falls and sports versus RTA), AIS grade (increase in incomplete lesions AIS B-D versus AIS A), severity (increase in tetraplegia versus paraplegia) and location (increase in cervical versus lumbar and thoracic injuries). CONCLUSIONS: A shift in trend is observed in the past 7 years regarding age of injuries (increase in those older than 9), etiology (increase in falls and sports versus RTA), AIS grade (increase in incomplete lesions AIS B-D versus AIS A), severity (increase in tetraplegia versus paraplegia) and location (increase in cervical). LEVEL OF EVIDENCE: IV.

Lesson learned in endoscopic endonasal dens resection for C1-C2 spinal cord decompression.

PURPOSE: Endoscopic endonasal approach (EEA) is the safest and most effective technique for odontoidectomy. Nevertheless, this kind of approach is yet not largely widespread. The aim of this study is to share with the scientific community some tips and tricks with our ten-year-old learned experience in endoscopic endonasal odontoidectomy (EEO), which remains a challenging surgical approach. MATERIAL AND METHODS: Our case series consists of twenty-one (10 males, 11 females; age range of 34-84 years) retrospectively analyzed patients with ventral spinal cord compression for non-reducible CVJ malformation, treated with EEA from July 2011 to March 2019. RESULTS: The results have recently been reported in a previous paper. The only intraoperative complication observed was intraoperative cerebrospinal fluid (CSF) leak (9.5%), without any sign of post-operative CSF leak. CONCLUSIONS: Considering our experience, EEO represents a valid and safe technique to decompress neural cervical structures. Despite its technical complexity, mainly due to the use of endoscope and the challenging surgical area, with this study we encourage the use of EEO displaying our experience-based surgical tips and tricks.

Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases.

The neuromuscular junction (NMJ) is a crucial structure that connects the cholinergic motor neurons to the muscle fibers and allows for muscle contraction and movement. Despite the interruption of the supraspinal pathways that occurs in spinal cord injury (SCI), the NMJ, innervated by motor neurons below the injury site, has been found to remain intact. This highlights the importance of studying the NMJ in rodent models of various nervous system disorders, such as amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). The NMJ is also involved in myasthenic disorders, such as myasthenia gravis (MG), and is vulnerable to neurotoxin damage. Thus, it is important to analyze the integrity of the NMJ in rodent models during the early stages of the disease, as this may allow for a better understanding of the condition and potential treatment options. The spinal cord also plays a crucial role in the functioning of the NMJ, as the junction relays information from the spinal cord to the muscle fibers, and the integrity of the NMJ could be disrupted by SCI. Therefore, it is vital to study SCI and muscle function when studying NMJ disorders. This review discusses the formation and function of the NMJ after SCI and potential interventions that may reverse or improve NMJ dysfunction, such as exercise, nutrition, and trophic factors.

Novel regenerative drug, SPG302 promotes functional recovery of diaphragm muscle activity after cervical spinal cord injury.

Spinal cord hemisection at C2 (C2 SH), sparing the dorsal column is widely used to investigate the effects of reduced phrenic motor neuron (PhMN) activation on diaphragm muscle (DIAm) function, with reduced DIAm activity on the injured side during eupnoea. Following C2 SH, recovery of DIAm EMG activity may occur spontaneously over subsequent days/weeks. Various strategies have been effective at improving the incidence and magnitude of DIAm recovery during eupnoea, but little is known about the effects of C2 SH on transdiaphragmatic pressure (Pdi ) during other ventilatory and non-ventilatory behaviours. We employ SPG302, a novel type of pegylated benzothiazole derivative, to assess whether enhancing synaptogenesis (i.e., enhancing spared local connections) will improve the incidence and the magnitude of recovery of DIAm EMG activity and Pdi function 14 days post-C2 SH. In anaesthetised Sprague-Dawley rats, DIAm EMG and Pdi were assessed during eupnoea, hypoxia/hypercapnia and airway occlusion prior to surgery (C2 SH or sham), immediately post-surgery and at 14 days post-surgery. In C2 SH rats, 14 days of DMSO (vehicle) or SPG302 treatments (i.p. injection) occurred. At the terminal experiment, maximum Pdi was evoked by bilateral phrenic nerve stimulation. We show that significant EMG and Pdi deficits are apparent in C2 SH compared with sham rats immediately after surgery. In C2 SH rats treated with SPG302, recovery of eupneic, hypoxia/hypercapnia and occlusion DIAm EMG was enhanced compared with vehicle rats after 14 days. Treatment with SPG302 also ameliorated Pdi deficits following C2 SH. In summary, SPG302 is an exciting new therapy to explore for use in spinal cord injuries. KEY POINTS: Despite advances in our understanding of the effects of cervical hemisection (C2 SH) on diaphragm muscle (DIAm) EMG activity, very little is understood about the impact of C2 SH on the gamut of ventilatory and non-ventilatory transdiaphragmatic pressures (Pdi ). Recovery of DIAm activity following C2 SH is improved using a variety of approaches, but very few pharmaceuticals have been shown to be effective. One way of improving DIAm recovery is to enhance the amount of latent local spared connections onto phrenic motor neurons. A novel pegylated benzothiazole derivative enhances synaptogenesis in a variety of neurodegenerative conditions. Here, using a novel therapeutic SPG302, we show that 14 days of treatment with SPG302 ameliorated DIAm EMG and Pdi deficits compared with vehicle controls. Our results show that SPG302 is a compound with very promising potential for use in improving functional outcomes post-spinal cord injury.

Quality of life in patients with malignant spinal cord compression: a systematic review.

INTRODUCTION: Malignant spinal cord compression (MSCC) is an oncological emergency that may result in a devastating combination of malignancy and disability. Existing quality of life (QoL) questionnaires commonly used in MSCC literature (EORTC QLQ-C30, BM-22, Brief Pain Inventory, and Spine Oncology Study Group Outcomes) may not capture all the commonly reported symptoms and lack specificity to MSCC. The primary objective of this systematic review is to determine unmet patient needs and underreported QoL issues and compile a comprehensive list of QoL issues. The secondary objective of this review is to compile all existing QoL tools and questionnaires and determine whether any QoL issues are not addressed in the existing tools currently used in the literature. METHODS: A literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases between 1946 and February 6, 2023, to compile all QoL issues and existing questionnaires used to assess QoL in patients with MSCC. All study designs were included given that they discussed QoL issues specific to patients with MSCC. RESULTS: The results of this systematic review identified the most frequently discussed QoL issues in the literature studying MSCC. This included direct symptoms of MSCC such as back pain, paralysis, limb weakness/numbness, and urinary/bowel incontinence. Indirect symptoms coming from radiotherapy treatment such as dysphagia, painful swallowing, mouth pain, dry mouth, diarrhea, fatigue, and nausea/vomiting were also noted. Other symptoms resulting from corticosteroid treatment included difficulty sleeping, blurring of vision, weight gain, and mood disturbance. Patients also experienced psychosocial issues such as anxiety, depression, emotional distress, low self-esteem, concerns about dependence on others, concerns about getting home, and fear about their prognosis and future. CONCLUSION: This review highlights the QoL issues specific to patients with MSCC and QoL tools capturing these issues. Relevance of QoL issues identified in this systematic review must be prospectively validated by patients and healthcare professionals with experience in treating MSCC.

Nanomedicine innovations in spinal cord injury management: Bridging the gap.

Spinal cord injury (SCI) has devastating effects on a person's physical, social, and professional well-being. It is a life-altering neurological condition that significantly impacts individuals and their caregivers on a socioeconomic level. Recent advancements in medical therapy have greatly improved the diagnosis, stability, survival rates, and overall well-being of SCI patients. However, there are still limited options available for enhancing neurological outcomes in these patients. The complex pathophysiology of SCI, along with the numerous biochemical and physiological changes that occur in the damaged spinal cord, contribute to this gradual improvement. Currently, there are no therapies that offer the possibility of recovery for SCI, although several therapeutic approaches are being developed. However, these therapies are still in the early stages and have not yet demonstrated effectiveness in repairing the damaged fibers, which hinders cellular regeneration and the full restoration of motor and sensory functions. Considering the importance of nanotechnology and tissue engineering in treating neural tissue injuries, this review focuses on the latest advancements in nanotechnology for SCI therapy and tissue healing. It examines research articles from the PubMed database that specifically address SCI in the field of tissue engineering, with an emphasis on nanotechnology as a therapeutic approach. The review evaluates the biomaterials used for treating this condition and the techniques employed to create nanostructured biomaterials.

Metal-organic framework materials promote neural differentiation of dental pulp stem cells in spinal cord injury.

Spinal cord injury (SCI) is accompanied by loss of Zn2+, which is an important cause of glutamate excitotoxicity and death of local neurons as well as transplanted stem cells. Dental pulp stem cells (DPSCs) have the potential for neural differentiation and play an immunomodulatory role in the microenvironment, making them an ideal cell source for the repair of central nerve injury, including SCI. The zeolitic imidazolate framework 8 (ZIF-8) is usually used as a drug and gene delivery carrier, which can release Zn2+ sustainedly in acidic environment. However, the roles of ZIF-8 on neural differentiation of DPSCs and the effect of combined treatment on SCI have not been explored. ZIF-8-introduced DPSCs were loaded into gelatin methacryloyl (GelMA) hydrogel and in situ injected into the injured site of SCI rats. Under the effect of ZIF-8, axon number and axon length of DPSCs-differentiated neuro-like cells were significantly increased. In addition, ZIF-8 protected transplanted DPSCs from apoptosis in the damaged microenvironment. ZIF-8 promotes neural differentiation and angiogenesis of DPSCs by activating the Mitogen-activated protein kinase (MAPK) signaling pathway, which is a promising transport nanomaterial for nerve repair.

The human dental apical papilla promotes spinal cord repair through a paracrine mechanism.

Traumatic spinal cord injury is an overwhelming condition that strongly and suddenly impacts the patient's life and her/his entourage. There are currently no predictable treatments to repair the spinal cord, while many strategies are proposed and evaluated by researchers throughout the world. One of the most promising avenues is the transplantation of stem cells, although its therapeutic efficiency is limited by several factors, among which cell survival at the lesion site. In our previous study, we showed that the implantation of a human dental apical papilla, residence of stem cells of the apical papilla (SCAP), supported functional recovery in a rat model of spinal cord hemisection. In this study, we employed protein multiplex, immunohistochemistry, cytokine arrays, RT- qPCR, and RNAseq technology to decipher the mechanism by which the dental papilla promotes repair of the injured spinal cord. We found that the apical papilla reduced inflammation at the lesion site, had a neuroprotective effect on motoneurons, and increased the apoptosis of activated macrophages/ microglia. This therapeutic effect is likely driven by the secretome of the implanted papilla since it is known to secrete an entourage of immunomodulatory or pro-angiogenic factors. Therefore, we hypothesize that the secreted molecules were mainly produced by SCAP, and that by anchoring and protecting them, the human papilla provides a protective niche ensuring that SCAP could exert their therapeutic actions. Therapeutic abilities of the papilla were demonstrated in the scope of spinal cord injury but could very well be beneficial to other types of tissue.

Pathophysiology of Spinal Cord Injury and Tissue Engineering Approach for Its Neuronal Regeneration: Current Status and Future Prospects.

A spinal cord injury (SCI) is a very debilitating condition causing loss of sensory and motor function as well as multiple organ failures. Current therapeutic options like surgery and pharmacotherapy show positive results but are incapable of providing a complete cure for chronic SCI symptoms. Tissue engineering, including neuroprotective or growth factors, stem cells, and biomaterial scaffolds, grabs attention because of their potential for regeneration and ability to bridge the gap in the injured spinal cord (SC). Preclinical studies with tissue engineering showed functional recovery and neurorestorative effects. Few clinical trials show the safety and efficacy of the tissue engineering approach. However, more studies should be carried out for potential treatment modalities. In this review, we summarize the pathophysiology of SCI and its current treatment modalities, including surgical, pharmacological, and tissue engineering approaches following SCI in preclinical and clinical phases.

Unique form of catheter malconnection following intrathecal baclofen surgery for spinal cord injury: a case report.

This case report concerns a patient suffering from traumatic spinal cord injury with severe spasticity treated with intrathecal baclofen therapy. After revision surgery for a confirmed catheter obstruction, progressive spasticity reappeared. Diagnostics demonstrated signs of catheter fracture or disconnection adjacent to the pump. During revision surgery, the silicone layer surrounding the sutureless pump connector was shown to be curled up, revealing the cause of dysfunction. As far as we know, this form of malconnection has not been reported before. Therefore, surgeons must be aware of this complication and additional inspection of the silicone connector prior to definite connection is advised.

Oropharyngeal Dysphagia in Acute Cervical Spinal Cord Injury: A Literature Review.

Dysphagia (swallowing impairment) is a frequent complication of cervical spinal cord injury (cSCI). Recently published national guidance in the UK on rehabilitation after traumatic injury confirmed that people with cSCI are at risk for dysphagia and require early evaluation while remaining nil by mouth [National Institute for Health and Care Excellence. Rehabilitation after traumatic injury (NG211), 2022, https://www.nice.org.uk/guidance/ng21 ]. While the pathogenesis and pathophysiology of dysphagia in cSCI remains unclear, numerous risk factors have been identified in the literature. This review aims to summarize the literature on the risk factors, presentation, assessment, and management of dysphagia in patients with cSCI. A bespoke approach to dysphagia management, that accounts for the multiple system impairment in cSCI, is presented; the overarching aim of which is to support effective management of dysphagia in patients with cSCI to prevent adverse clinical consequences.

Composite Fibrin/Carbon Microfiber Implants for Bridging Spinal Cord Injury: A Translational Approach in Pigs.

Biomaterials may enhance neural repair after spinal cord injury (SCI) and testing their functionality in large animals is essential to achieve successful clinical translation. This work developed a porcine contusion/compression SCI model to investigate the consequences of myelotomy and implantation of fibrin gel containing biofunctionalized carbon microfibers (MFs). Fourteen pigs were distributed in SCI, SCI/myelotomy, and SCI/myelotomy/implant groups. An automated device was used for SCI. A dorsal myelotomy was performed on the lesion site at 1 day post-injury for removing cloths and devitalized tissue. Bundles of MFs coated with a conducting polymer and cell adhesion molecules were embedded in fibrin gel and used to bridge the spinal cord cavity. Reproducible lesions of about 1 cm in length were obtained. Myelotomy and lesion debridement caused no further neural damage compared to SCI alone but had little positive effect on neural regrowth. The MFs/fibrin gel implant facilitated axonal sprouting, elongation, and alignment within the lesion. However, the implant also increased lesion volume and was ineffective in preventing fibrosis, thus precluding functional neural regeneration. Our results indicate that myelotomy and lesion debridement can be advantageously used for implanting MF-based scaffolds. However, the implants need refinement and pharmaceuticals will be necessary to limit scarring.

The Application of Biomaterials in Spinal Cord Injury.

The spinal cord and the brain form the central nervous system (CNS), which is the most important part of the body. However, spinal cord injury (SCI) caused by external forces is one of the most difficult types of neurological injury to treat, resulting in reduced or even absent motor, sensory and autonomic functions. It leads to the reduction or even disappearance of motor, sensory and self-organizing nerve functions. Currently, its incidence is increasing each year worldwide. Therefore, the development of treatments for SCI is urgently needed in the clinic. To date, surgery, drug therapy, stem cell transplantation, regenerative medicine, and rehabilitation therapy have been developed for the treatment of SCI. Among them, regenerative biomaterials that use tissue engineering and bioscaffolds to transport cells or drugs to the injured site are considered the most promising option. In this review, we briefly introduce SCI and its molecular mechanism and summarize the application of biomaterials in the repair and regeneration of tissue in various models of SCI. However, there is still limited evidence about the treatment of SCI with biomaterials in the clinic. Finally, this review will provide inspiration and direction for the future study and application of biomaterials in the treatment of SCI.

Current Concepts of Biomaterial Scaffolds and Regenerative Therapy for Spinal Cord Injury.

Spinal cord injury (SCI) is a catastrophic condition associated with significant neurological deficit and social and financial burdens. It is currently being managed symptomatically, with no real therapeutic strategies available. In recent years, a number of innovative regenerative strategies have emerged and have been continuously investigated in preclinical research and clinical trials. In the near future, several more are expected to come down the translational pipeline. Among ongoing and completed trials are those reporting the use of biomaterial scaffolds. The advancements in biomaterial technology, combined with stem cell therapy or other regenerative therapy, can now accelerate the progress of promising novel therapeutic strategies from bench to bedside. Various types of approaches to regeneration therapy for SCI have been combined with the use of supportive biomaterial scaffolds as a drug and cell delivery system to facilitate favorable cell-material interactions and the supportive effect of neuroprotection. In this review, we summarize some of the most recent insights of preclinical and clinical studies using biomaterial scaffolds in regenerative therapy for SCI and summarized the biomaterial strategies for treatment with simplified results data. One hundred and sixty-eight articles were selected in the present review, in which we focused on biomaterial scaffolds. We conducted our search of articles using PubMed and Medline, a medical database. We used a combination of "Spinal cord injury" and ["Biomaterial", or "Scaffold"] as search terms and searched articles published up until 30 April 2022. Successful future therapies will require these biomaterial scaffolds and other synergistic approaches to address the persistent barriers to regeneration, including glial scarring, the loss of a structural framework, and biocompatibility. This database could serve as a benchmark to progress in future clinical trials for SCI using biomaterial scaffolds.

The Impact of Biomaterial Surface Properties on Engineering Neural Tissue for Spinal Cord Regeneration.

Tissue engineering for spinal cord injury (SCI) remains a complex and challenging task. Biomaterial scaffolds have been suggested as a potential solution for supporting cell survival and differentiation at the injury site. However, different biomaterials display multiple properties that significantly impact neural tissue at a cellular level. Here, we evaluated the behavior of different cell lines seeded on chitosan (CHI), poly (ε-caprolactone) (PCL), and poly (L-lactic acid) (PLLA) scaffolds. We demonstrated that the surface properties of a material play a crucial role in cell morphology and differentiation. While the direct contact of a polymer with the cells did not cause cytotoxicity or inhibit the spread of neural progenitor cells derived from neurospheres (NPCdn), neonatal rat spinal cord cells (SCC) and NPCdn only attached and matured on PCL and PLLA surfaces. Scanning electron microscopy and computational analysis suggested that cells attached to the material's surface emerged into distinct morphological populations. Flow cytometry revealed a higher differentiation of neural progenitor cells derived from human induced pluripotent stem cells (hiPSC-NPC) into glial cells on all biomaterials. Immunofluorescence assays demonstrated that PCL and PLLA guided neuronal differentiation and network development in SCC. Our data emphasize the importance of selecting appropriate biomaterials for tissue engineering in SCI treatment.

[Recovery of spinal cord functions after experimental complete crossection under the effect of chitosan polymeric compounds]. / Vozmozhnosti klinicheskogo vosstanovleniya funktsii spinnogo mozga pri ego polnom peresechenii v eksperimente pod vozdeistviem polimernykh soedinenii khitozana.

Currently, there is no effective method of treating complete spinal cord intersection. One of the promising experimental approaches is substances promoting repair and fusion of axonal membranes. OBJECTIVE: To study clinical and functional recovery in experimental animals with transected spinal cord after management with photo-cross-linked chitosan in a homogeneous mixture with polyethylene glycol. MATERIAL AND METHODS: We studied 20 rabbits with a model of complete spinal cord transection at the level of Th9. There were control and experimental groups (n=10; n=10). In the experimental group, we intraoperatively injected photo-cross-linked chitosan in a homogeneous mixture with polyethylene glycol. Neurological status was assessed using the modified Basso Beattie Bresnahan scale. Histological examination was performed after removing the animals from the experiment. RESULTS: In the experimental group, significant regression of neurological disorders was accompanied by partial recovery of movements, sensitivity and control of pelvic functions by the 30th day of the experiment. There was no mortality in the experimental group. Paraplegia and anesthesia persisted in the control group while mortality was 40% (n=4). Histological analysis in the main group revealed axonal «bridges¼ in the area of injury and spread of DiI dye through this area. CONCLUSION: These phenomena confirm the positive effect of chitosan and polyethylene glycol on functional recovery after experimental spinal cord injury. These data are consistent with histological findings.

Decellularised extracellular matrix-based biomaterials for repair and regeneration of central nervous system.

The central nervous system (CNS), consisting of the brain and spinal cord, regulates the mind and functions of the organs. CNS diseases, leading to changes in neurological functions in corresponding sites and causing long-term disability, represent one of the major public health issues with significant clinical and economic burdens worldwide. In particular, the abnormal changes in the extracellular matrix under various disease conditions have been demonstrated as one of the main factors that can alter normal cell function and reduce the neuroregeneration potential in damaged tissue. Decellularised extracellular matrix (dECM)-based biomaterials have been recently utilised for CNS applications, closely mimicking the native tissue. dECM retains tissue-specific components, including proteoglycan as well as structural and functional proteins. Due to their unique composition, these biomaterials can stimulate sensitive repair mechanisms associated with CNS damages. Herein, we discuss the decellularisation of the brain and spinal cord as well as recellularisation of acellular matrix and the recent progress in the utilisation of brain and spinal cord dECM.