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![Schematic illustration of IONP delivery combined with external magnetic field for SCI treatment. (A) Schematic showing that magnetic NPs targeting guided into cells under the action of an external magnetic field. Copyright 2009 nature nanotechnology [60]. (B, C) Prussian blue staining for iron and TEM imagese exhibiting the aggregations of IONPs in the lesion stie mediated by external magnetic field. (D) Mechanism of free radical scavenging by IONPs. (E) Showing 3D simulation of the distribution changes of superparamagnetic iron oxide-labelled stem cell under normalized magnetic gradient force (X-Z-plane), and the characteristics of superparamagnetic iron oxide NPs. (F) Distributions of superparamagnetic iron oxide-labelled cells with or without magnetic field. (B, C, D) Copyright 2013 International Journal of Nanomedicine [34]. (E-F) Copyright 2015 Nanoscale [61]. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)](publication/366376618/figure/fig4/AS:11431281112072273@1673287251262/Schematic-illustration-of-IONP-delivery-combined-with-external-magnetic-field-for-SCI.jpg)
Schematic illustration of IONP delivery combined with external magnetic field for SCI treatment. (A) Schematic showing that magnetic NPs targeting guided into cells under the action of an external magnetic field. Copyright 2009 nature nanotechnology [60]. (B, C) Prussian blue staining for iron and TEM imagese exhibiting the aggregations of IONPs in the lesion stie mediated by external magnetic field. (D) Mechanism of free radical scavenging by IONPs. (E) Showing 3D simulation of the distribution changes of superparamagnetic iron oxide-labelled stem cell under normalized magnetic gradient force (X-Z-plane), and the characteristics of superparamagnetic iron oxide NPs. (F) Distributions of superparamagnetic iron oxide-labelled cells with or without magnetic field. (B, C, D) Copyright 2013 International Journal of Nanomedicine [34]. (E-F) Copyright 2015 Nanoscale [61]. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Source publication
Spinal cord injuries (SCIs) are devastating. In SCIs, a powerful traumatic force impacting the spinal cord results in the permanent loss of nerve function below the injury level, leaving the patient paralyzed and wheelchair-bound for the remainder of his/her life. Unfortunately, clinical treatment that depends on surgical decompression appears to b...
Contexts in source publication
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... oxide NPs (IONPs), such as Fe 3 O 4 and Fe 2 O 3, are also easy to produce and are widely used for imaging, drug delivery, and photothermal therapy [58,59]. When combined with external electromagnetic fields, IONPs play an effective role in transfection and delivery in the treatment of SCI (Fig. 5A) [60]. Ajay Pal et al. [34] confirmed that IONP exposure in a magnetic field effectively promoted the recovery of spinal function by attenuating free radical-induced damage. The study found that the magnetic field significantly increased the retention and accumulation of IONPs at the damage center ( Fig. 5B and C) and that the enhanced ...
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... and delivery in the treatment of SCI (Fig. 5A) [60]. Ajay Pal et al. [34] confirmed that IONP exposure in a magnetic field effectively promoted the recovery of spinal function by attenuating free radical-induced damage. The study found that the magnetic field significantly increased the retention and accumulation of IONPs at the damage center ( Fig. 5B and C) and that the enhanced antioxidant capacity was associated with alterations in the electron spin relaxation state caused by the magnetic field (Fig. 5D). Their subsequent work showed that exposure to a magnetic field may further stretch axonal terminals and cause sprouting, thus promoting ...
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... of spinal function by attenuating free radical-induced damage. The study found that the magnetic field significantly increased the retention and accumulation of IONPs at the damage center ( Fig. 5B and C) and that the enhanced antioxidant capacity was associated with alterations in the electron spin relaxation state caused by the magnetic field (Fig. 5D). Their subsequent work showed that exposure to a magnetic field may further stretch axonal terminals and cause sprouting, thus promoting ...
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... transfection. S arka Kubinov a et al. [61] used superparamagnetic iron oxide NPs to label MSCs for intrathecal transplantation therapy and found significantly higher concentrations of superparamagnetic iron oxide-labelled stem cells in the vicinity of the damaged lesions under magnetic guidance, achieving effective stem cell delivery ( Fig. 5E and F). Similar studies were conducted by Aleem Ahmed Khan et al. [62] and Jung-Keug Park et al. [63]. Stuart et al. [64] applied a static/oscillating magnetic field to promote in vivo transfection of oligodendrocyte precursor cell transplant cells. Magnetic NP-mediated transfection improved transfection efficiency and did not affect cell ...
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... reduced BSCB leakage. Shi et al. [117] synthesized cationic PEGylated amphiphilic octadecyl-quaternizedlysine-modified chitosan (PEG-OQLCS) and cationic TAT-conjugated amphiphilic octadecyl-quaternizedlysine-modified chitosan (TAT-OQLCS) and then mixed the two amphipathic lipids with cholesterol and PLGA NPs to self-assemble polymeric liposomes (Fig. 15A). The core/shell NPs loaded with cyclosporin A could facilitate the transport of drugs across the BSCB by TAT-targeted binding and then promote their immunosuppressive and neuroprotective ...
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... and endothelial cell death. Zhang et al. [121] synthesized 69.8-nm lipid-polymer shell/core NPs composed of a poly[propargyl(methylthio) acetate-coethylene glycol di(β-mercaptopropionate)] (poly(PMT-co-EGDM)) core, which was prepared by simple thiol-yne click polymerization, and a protective lipid outer layer consisting of PEG-DSPE and lecithin (Fig. 15B). Because the structure contained a high density of thioether groups, the NPs could scavenge and eliminate ROS to exhibit antiapoptotic and anti-inflammatory roles in SCI therapy. At 28 days postinjury, the locomotor function was significantly improved in the NPs treated group, as assessed by the BBB ...
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Background
Spinal cord injury results in the interruption of neuronal conduction in the spinal cord, a condition that occurs in 0.1% of the world's population. This results in severe limitations in autonomy including locomotor function. Its recovery can be pursued through conventional isolated physiotherapeutic rehabilitation (overground walking t...
Citations
... Phase I/II clinical trials using nanoparticle-drug conjugates targeting brain tumors through the blood-brain barrier (BBB) are underway, demonstrating the potential of nanoparticles in traversing barriers. Nanoparticles from biological (exosomes) and synthetic (lipids) sources have shown promise in improving motor functions and restoring tight junctions to attenuate BSCB leakage post SCI [96]. Various types of nanoparticles, including metals, polymers, and lipids, have been explored as tracers and drug delivery systems in SCI, showing significant reductions in inflammatory factors and enhancement of neuronal regeneration [97]. ...
Spinal cord injury is a complicated medical condition both from the clinician’s point of view in terms of management and from the patient’s perspective in terms of unsatisfactory recovery. Depending on the severity, this disorder can be devastating despite the rapid and appropriate use of modern imaging techniques and convenient surgical spinal cord decompression and stabilization. In this context, there is a mandatory need for novel adjunctive therapeutic approaches to classical treatments to improve rehabilitation chances and clinical outcomes. This review offers a new and original perspective on therapies targeting the microglia, one of the most relevant immune cells implicated in spinal cord disorders. The first part of the manuscript reviews the anatomical and pathophysiological importance of the blood-spinal cord barrier components, including the role of microglia in post-acute neuroinflammation. Subsequently, the authors present the emerging therapies based on microglia modulation, such as cytokines modulators, stem cell, microRNA, and nanoparticle-based treatments that could positively impact spinal cord injury management. Finally, future perspectives and challenges are also highlighted based on the ongoing clinical trials related to medications targeting microglia.
... The nanoparticle penetration of the blood-spinal cord barrier (B-SCB) and subsequent parenchymal accumulation is a complex interplay between NP size and delivery methodology, cargo, and /or the target cell/mechanism of interest [8][9][10]. Larger NPs, such as those sized 190 nm and 500 nm, have been shown to induce less cell membrane damage and limit infiltration of pro-inflammatory monocytes into the injury site, improving functional recovery in SCI rodents [11,12]. ...
Purpose of this review: Manipulating or re-engineering the damaged human spinal cord to achieve neuro-recovery is one of the foremost challenges of modern science. Addressing the restricted permission of neural cells and topographically organised neural tissue for self-renewal and spontaneous regeneration, respectively, is not straightforward, as exemplified by rare instances of translational success. This review assembles an understanding of advances in nanomedicine for spinal cord injury (SCI) and related clinical indications of relevance to attempts to design, engineer, and target nanotechnologies to multiple molecular networks. Recent findings: Recent research provides a new understanding of the health benefits and regulatory landscape of nanomedicines based on a background of advances in mRNA-based nanocarrier vaccines and quantum dot-based optical imaging. In relation to spinal cord pathology, the extant literature details promising advances in nanoneuropharmacology and regenerative medicine that inform the present understanding of the nanoparticle (NP) biocompatibility–neurotoxicity relationship. In this review, the conceptual bases of nanotechnology and nanomaterial chemistry covering organic and inorganic particles of sizes generally less than 100 nm in diameter will be addressed. Regarding the centrally active nanotechnologies selected for this review, attention is paid to NP physico-chemistry, functionalisation, delivery, biocompatibility, biodistribution, toxicology, and key molecular targets and biological effects intrinsic to and beyond the spinal cord parenchyma. Summary: The advance of nanotechnologies for the treatment of refractory spinal cord pathologies requires an in-depth understanding of neurobiological and topographical principles and a consideration of additional complexities involving the research’s translational and regulatory landscapes.
... It is well-documented that timely therapeutic intervention through ROS scavenging and inflammation suppression at the initial phase of SCI can significantly improve neurological and functional recuperation [14,18,[20][21][22][23]. Recently, the utilization of nano-biomaterials as a therapeutic approach for SCI has garnered considerable interest [5,15,[24][25][26]. Among them, selenium (Se)-based nanoparticles (NPs) have emerged as promising candidates due to their capacity for scavenging ROS and mitigating inflammation [27][28][29]. ...
Background
Therapeutic strategies based on scavenging reactive oxygen species (ROS) and suppressing inflammatory cascades are effective in improving functional recovery after spinal cord injury (SCI). However, the lack of targeting nanoparticles (NPs) with powerful antioxidant and anti-inflammatory properties hampers the clinical translation of these strategies. Here, CD44-targeting hyaluronic acid-selenium (HA-Se) NPs were designed and prepared for scavenging ROS and suppressing inflammatory responses in the injured spinal cord, enhancing functional recovery.
Results
The HA-Se NPs were easily prepared through direct reduction of seleninic acid in the presence of HA. The obtained HA-Se NPs exhibited a remarkable capacity to eliminate free radicals and CD44 receptor-facilitated internalization by astrocytes. Moreover, the HA-Se NPs effectively mitigated the secretion of proinflammatory cytokines (such as IL-1β, TNF-α, and IL-6) by microglia cells (BV2) upon lipopolysaccharide-induced inflammation. In vivo experiments confirmed that HA-Se NPs could effectively accumulate within the lesion site through CD44 targeting. As a result, HA-Se NPs demonstrated superior protection of axons and neurons within the injury site, leading to enhanced functional recovery in a rat model of SCI.
Conclusions
These results highlight the potential of CD44-targeting HA-Se NPs for SCI treatment.
... Despite the potential for organic nanomaterials to be customized to suit the specific microenvironment of live organisms in terms of their components and capabilities, there are still unresolved concerns over their immunogenicity when they are used over extended periods of time. Bioderived nanomaterials derived from living organic cells, including exosomes and membrane-coated NPs with highly non-immunogenic properties, can be used to prevent immune monitoring during systemic administration [106]. Exosomes with an average diameter of 50-200 nm contain an array of membrane-associated, high-order oligomeric proteins (e.g., CD63/CD81/CD9, heat shock protein 60, and actin-interacting protein 1/ALG-2-interacting protein X), nucleic acids (e.g., DNA, mRNA, and noncoding RNA), lipids (e.g., cholesterol, phosphatidylserine, and phosphatidylinositol), and metabolites (lactate, glutamate, acetate, stearate, palmitate, and amino acids) [106,107]. ...
... Bioderived nanomaterials derived from living organic cells, including exosomes and membrane-coated NPs with highly non-immunogenic properties, can be used to prevent immune monitoring during systemic administration [106]. Exosomes with an average diameter of 50-200 nm contain an array of membrane-associated, high-order oligomeric proteins (e.g., CD63/CD81/CD9, heat shock protein 60, and actin-interacting protein 1/ALG-2-interacting protein X), nucleic acids (e.g., DNA, mRNA, and noncoding RNA), lipids (e.g., cholesterol, phosphatidylserine, and phosphatidylinositol), and metabolites (lactate, glutamate, acetate, stearate, palmitate, and amino acids) [106,107]. Encapsulated biomolecules play a crucial role in enhancing intercellular communication activities, consequently facilitating the fusion of cell membranes, improving the efficiency of delivery and transfection, and replenishing nutrients in areas that have been damaged [107,108]. The utilization of cell membrane-based nanotechnology has come to be as a promising strategy for enhancing the delivery of pharmaceuticals. ...
... Cell membranes are commonly isolated from various types of cells, including red blood cells, white blood cells, stem cells, platelets, macrophages, and lymphocytes. Membrane-coated NPs, thus, constitute biomimetic NPs with the ability to prolong their circulation times and achieve specific and sensitive targeting [106]. ...
Promoting the recovery of neurological function in patients with traumatic spinal cord injury (TSCI) remains challenging. The balance between astrocyte-mediated neurotrophic and pro-inflammatory responses is critical for TSCI repair. Recently, the utilization of nanomaterials has been considerably explored in immunological reconstructive techniques that specifically target astrocyte-mediated inflammation, yielding positive outcomes. In this review, we aim to condense the present knowledge regarding the astrocyte-mediated inflammation following TSCI. We then review the various categories of nanomaterials utilized in the management of astrocyte-mediated inflammation in TSCI and conclude by summarizing their functions and advantages to offer novel insights for the advancement of effective clinical strategies targeting TSCI.
... Spinal cord injury (SCI) is a central nervous system traumatic disorder characterized by a high disability rate, resulting in impairments [1,2]. SCI resulting from vehicular crashes, gunshot wounds, high-altitude falling injuries and heavy falling injuries is the most pr from diverse etiologies and manifests varying degrees of sensory and motor functional evalent form in clinical practice [3]. According to clinical statistics, the global annual prevalence of SCI ranges from 10.4 to 83 cases per million population [4]. ...
Spinal cord injury (SCI) is a serious central nervous system (CNS) injury disease related to hypoxia-ischemia and inflammation. It is characterized by excessive reactive oxygen species (ROS) production, oxidative damage to nerve cells, and mitochondrial dysfunction. Mitochondria serve as the primary cellular origin of ROS, wherein the electron transfer chain complexes within oxidative phosphorylation frequently encounter electron leakage. These leaked electrons react with molecular oxygen, engendering the production of ROS, which culminates in the occurrence of oxidative stress. Oxidative stress is one of the common forms of secondary injury after SCI. Mitochondrial oxidative stress can lead to impaired mitochondrial function and disrupt cellular signal transduction pathways. Hence, restoring mitochondrial electron transport chain (ETC), reducing ROS production and enhancing mitochondrial function may be potential strategies for the treatment of SCI. This article focuses on the pathophysiological role of mitochondrial oxidative stress in SCI and evaluates in detail the neuroprotective effects of various mitochondrial-targeted antioxidant therapies in SCI, including both drug and non-drug therapy. The objective is to provide valuable insights and serve as a valuable reference for future research in the field of SCI.
... Nanomaterials are also opening new avenues in SCI treatment. Its possible mechanisms of action are the direct protection and maintenance of nerve cells, protecting nerve cells by improving the damaged microenvironment during the process of secondary injury, or facilitating neural regeneration [123]. Neurostimulation combined with rehabilitation has recently been applied to patients with complete and incomplete SCI, with promising results. ...
Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. Cell therapy, particularly with mesenchymal stem cells (MSCs), holds significant promise for TSCI treatment. This systematic review aims to analyze the efficacy, safety, and therapeutic potential of MSC-based cell therapies in TSCI. A comprehensive search of PUBMED and COCHRANE databases until February 2023 was conducted, combining terms such as “spinal cord injury,” “stem cells,” “stem cell therapy,” “mesenchymal stem cells,” and “traumatic spinal cord injury”. Among the 53 studies initially identified, 22 (21 clinical trials and 1 case series) were included. Findings from these studies consistently demonstrate improvements in AIS (ASIA Impairment Scale) grades, sensory scores, and, to a lesser extent, motor scores. Meta-analyses further support these positive outcomes. MSC-based therapies have shown short- and medium-term safety, as indicated by the absence of significant adverse events within the studied timeframe. However, caution is required when drawing generalized recommendations due to the limited scientific evidence available. Further research is needed to elucidate the long-term safety and clinical implications of these advancements. Although significant progress has been made, particularly with MSC-based therapies, additional studies exploring other potential future therapies such as gene therapies, neurostimulation techniques, and tissue engineering approaches are essential for a comprehensive understanding of the evolving TSCI treatment landscape.
Spinal cord injury results in the loss of sensory, motor, and autonomic functions, which almost always produces permanent physical disability. Thus, in the search for more effective treatments than those already applied for years, which are not entirely efficient, researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach, seeking to promote neuronal recovery after spinal cord injury. Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and, consequently, boosting functional recovery. Although the majority of experimental research has been conducted in rodents, there is increasing recognition of the importance, and need, of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans. This article is a literature review from databases (PubMed, Science Direct, Elsevier, Scielo, Redalyc, Cochrane, and NCBI) from 10 years ago to date, using keywords (spinal cord injury, cell therapy, non-human primates, humans, and bioengineering in spinal cord injury). From 110 retrieved articles, after two selection rounds based on inclusion and exclusion criteria, 21 articles were analyzed. Thus, this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans, aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
Spinal cord injuries are very common worldwide, leading to permanent nerve function loss with devastating effects in the affected patients. The challenges and inadequate results in the current clinical treatments are leading scientists to innovative neural regenerative research. Advances in nanoscience and neural tissue engineering have opened new avenues for spinal cord injury (SCI) treatment. In order for designed nerve guidance conduit (NGC) to be functionally useful, it must have ideal scaffold properties and topographic features that promote the linear orientation of damaged axons. In this study, it is aimed to develop channeled polycaprolactone (PCL)/Poly-D,L-lactic-co-glycolic acid (PLGA) hybrid film scaffolds, modify their surfaces by IKVAV pentapeptide/gold nanoparticles (AuNPs) or polypyrrole (PPy) and investigate the behavior of motor neurons on the designed scaffold surfaces in vitro under static/bioreactor conditions. Their potential to promote neural regeneration after implantation into the rat SCI by shaping the film scaffolds modified with neural factors into a tubular form is also examined. It is shown that channeled groups decorated with AuNPs highly promote neurite orientation under bioreactor conditions and also the developed optimal NGC (PCL/PLGA G1-IKVAV/BDNF/NGF-AuNP50) highly regenerates SCI. The results indicate that the designed scaffold can be an ideal candidate for spinal cord regeneration.
