Search

Spinal cord injury (SCI) leads to significant bone loss resulting in osteoporosis and an increased risk of fractures below the level of injury. It is imperative to screen for osteoporosis in all individuals with SCI starting immediately after the acute injury. Although data are limited, clinicians are encouraged to discuss preventative treatment in the acute SCI period and to treat osteoporosis when diagnosed., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Spinal Cord Injury (SCI) is a significant neurological disorder that can result in severe motor and cognitive impairments. Neuronal regeneration and functional recovery are critical aspects of SCI treatment, with calcium signaling being a crucial indicator of neuronal excitability. In this study, we utilized a murine model to investigate the effects of targeted wireless electrical stimulation (ES) on neuronal activity following SCI. After establishing a complete SCI model in normal mice, flexible electrodes were implanted, and targeted wireless ES was administered to the injury site. We employed fiber-optic photometric in vivo calcium imaging to monitor calcium signals in pyramidal neurons within the CA3 region of the hippocampus and the M1 region of the primary motor cortex. The experimental results demonstrated a significant reduction in calcium signals in CA3 and M1 pyramidal neurons following SCI (reduced by 76 % and 59 %, in peak respectively). However, the application of targeted wireless ES led to a marked increase in calcium signals in these neurons (increased by 118 % and 69 %, in peak respectively), indicating a recovery of calcium activity. These observations suggest that wireless ES has a positive modulatory effect on the excitability of pyramidal neurons post-SCI. Understanding these mechanisms is crucial for developing therapeutic strategies aimed at enhancing neuronal recovery and functional restoration following spinal cord injuries., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) is a profound medical condition that significantly hampers motor function, imposing substantial limitations on daily activities and exerting a considerable financial burden on patients and their families. The constrained regenerative capacity of endogenous spinal cord tissue, exacerbated by the inflammatory response following the initial trauma, poses a formidable obstacle to effective therapy. Recent advancements in the field, stem cells, biomaterials, and molecular therapy, show promising outcomes. This review provides a comprehensive analysis of tissue engineering and regenerative medicine approaches for SCI treatment, including cell transplantation, tissue-engineered construct implantation, and other potential therapeutic strategies. Additionally, it sheds light on preclinical animal studies and recent clinical trials incorporating these modalities, providing a glimpse into the evolving landscape of SCI management. STATEMENT OF SIGNIFICANCE: The investigation into spinal cord injury (SCI) treatments focuses on reducing long-term impacts by targeting scar inhibition and enhancing regeneration through stem cells, with or without growth factors. Induced pluripotent stem cells (iPSCs) show promise for autologous use, with clinical trials confirming their safety. Challenges include low cell viability and difficulty in targeted differentiation. Biomaterial scaffolds hold potential for improving cell viability and integration, and extracellular vesicles (EVs) are emerging as a novel therapy. While EV research is in its early stages, stem cell trials demonstrate safety and potential recovery. Advancing tissue engineering approaches with biomaterial scaffolds is crucial for human trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Spinal cord injury (SCI) affects around 18,000 individuals annually, representing nearly one-third of all paralysis cases. Stem cell therapy, a focal point in contemporary neuroregeneration research for SCI treatment, holds potential in leveraging undifferentiated stem cells to regenerate damaged tissues. This study seeks to comprehensively analyze current clinical trials exploring the potential use of stem cells in treating spinal cord injuries., Methods: A data retrieval approach examined the ClinicalTrials.gov database using the terms "spinal cord injury" and "stem cells." Exclusion criteria eliminated studies not recruiting, terminated prematurely, suspended, withdrawn, or of unknown status. Data for each trial, including ClinicalTrial.gov NCT identifier, title, intervention details, initiation/completion dates, and sample size, were systematically collected. Literature searches on PubMed.gov were conducted for completed trials with results., Results: Thirty clinical trials were analyzed, with 20 completed and six with published results on PubMed.gov. Interventions included 20 biological (66.7%), 6 procedural (20%), and 4 drug interventions (13.3%). Stem cell sources varied, including bone marrow (46.7%), umbilical cells (20%), adipose tissue (20%), embryonic cells (6.7%), and neural cells (6.7%). Trials spanned 2005 to 2022, with 11 (36.7%) commencing in or after 2017. Among six trials with results, 50% used bone marrow-derived stem cells., Conclusions: The promising potential of stem cells in neuroregenerative SCI treatment necessitates further exploration through large-scale, multicenter clinical trials to enhance understanding and guide wider adoption of this emerging treatment paradigm., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) is a debilitating condition that can result in significant functional impairment and loss of quality of life. There is a growing interest in developing new therapies for SCI, and hydrogel-based multimodal therapeutic strategies have emerged as a promising approach. They offer several advantages for SCI repair, including biocompatibility, tunable mechanical properties, low immunogenicity, and the ability to deliver therapeutic agents. This article provides an overview of the recent advances in hydrogel-based therapy strategies for SCI repair, particularly within the past three years. We summarize the SCI hydrogels with varied characteristics such as phase-change hydrogels, self-healing hydrogel, oriented fibers hydrogel, and self-assembled microspheres hydrogel, as well as different functional hydrogels such as conductive hydrogels, stimuli-responsive hydrogels, adhesive hydrogel, antioxidant hydrogel, sustained-release hydrogel, etc. The composition, preparation, and therapeutic effect of these hydrogels are briefly discussed and comprehensively evaluated. In the end, the future development of hydrogels in SCI repair is prospected to inspire more researchers to invest in this promising field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To explore the influence of intermittent theta burst stimulation (iTBS) dual-target stimulation on lower limb function in patients with incomplete spinal cord injury (iSCI)., Methods: A randomized, single -blind, sham-controlled trial was used in this study. Thirty iSCI patients with lower limb dysfunction meeting the inclusion criteria were randomly divided into a sham group and an iTBS group, with 15 cases in each group. The iTBS group received conventional rehabilitation therapy combined with iTBS dual-target stimulation on the central cerebral sulcus and the nerve root of the spinal cord injury segment. The sham group was treated with conventional rehabilitation therapy combined with iTBS dual-target sham stimulation therapy. Comprehensive functional assessment was performed on all patients before treatment, on the day 3 and day 21 of treatment. The main evaluation indicators were as follows: amplitude and latency of motor-evoked potential (MEP) in the anterior tibial muscles of both lower limbs, latency of sensory-evoked potential (SEP) of both lower limbs, knee flexor strength and knee extensor strength, lower extremity motor score (LEMS), lower extremity sensory score, spinal cord independence measure (SCIM) score, and gait parameters (stride speed, stride frequency, stride length, and ground reaction force)., Results: On day 21 of treatment, in the iTBS group, the MEP amplitude of the anterior tibial muscles increased, the latency of MEP shortened, knee flexor strength and knee extensor strength increased, and the LEMS and SCIM score of both lower limbs increased. In addition, there were statistically significant differences in the muscle strength of the knee flexion muscle, knee extensor muscle, MEP amplitude, LEMS, and SCIM between the 2 groups (P < 0.05). Among the 10 patients who could walk with an assisted walker, the step length and step frequency of the iTBS group were increased compared with the sham group after treatment (P < 0.01), and the ground reaction force was increased (P < 0.05). There was no significant difference in the lower extremity sensory score of the lower limbs between the 2 groups (P > 0.05)., Conclusions: ITBS dual-target stimulation can significantly improve the motor function of both lower limbs in patients with iSCI but does not significantly improve the sensory function of both lower limbs. Therefore, this treatment mode may participate in the reconstruction and repair of some nerve circuits in patients with iSCI. In addition, iTBS dual-target stimulation can improve the ability of iSCI patients to perform daily living., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To explore the effect of the mindfulness-based stress reduction (MBSR) practice on sleep quality and perceived stress in patients with spinal cord injury (SCI)., Method: A total of 104 patients with SCI (diagnosed via imaging and clinical symptoms) admitted to our hospital between January 2020 and December 2022 were selected as the study participants. The patients were randomly divided into two groups: the MBSR (observation) group and the control group. The observation group received MBSR therapy and routine nursing, and the control group received music training therapy and routine nursing. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and the perceived stress score was used to evaluate stress experienced by the patients at three timepoints: before intervention, 4 weeks and 8weeks after intervention., Results: Compared with before intervention, the PSQI scores of both the control group and intervention group participants significantly decreased after intervention(P < 0.01). Compared with the 4 weeks after intervention, the PSQI scores of both groups of participants decreased in the 8 weeks after intervention(P < 0.01). There was a significant difference in PSQI scores between the two groups of participants at 4 and 8 weeks after intervention(P < 0.01). Compared with before intervention, the average perceived stress score of both the control group and intervention group participants significantly decreased after intervention(P < 0.05). Compared with the 4 weeks after intervention, the average perceived stress score of both groups of participants decreased in the 8 weeks after intervention(P < 0.01). There was a significant difference in average perceived stress score between the two groups of participants at 4(P < 0.05) and 8 weeks(P < 0.01) after intervention(P < 0.01)., Conclusion: The use of MBSR therapy could effectively improve patient sleep quality and reduce perceived stress., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Traumatic spinal cord injury (TSCI) is a devastating condition that may result to lifelong complications that affect patient outcome and quality of life. Because of the increasing incidence of TSCI, it is important to comprehend the extent of this condition in terms of demographics, mechanism, and degree of disability to raise awareness and develop strategies in approaching care for these patients. There is a lack of information regarding data on TSCI in Southeast Asia, especially in the Philippines. This study aims to describe the clinical characteristics and outcomes of patients with TSCI in a tertiary care hospital in the Philippines., Methods: This is a retrospective descriptive cohort study in individuals aged 18 years older who were admitted for TSCI in a Philippine tertiary care hospital between 2022 and 2023. Of 118 admitted patients, 100 patients were included in the study. The data were obtained from the review of patients' medical records. Demographics of TSCI, mechanism, presenting clinical characteristics, American Spinal Injury Association Impairment Scale (AIS) grade, radiographic findings, outcomes, and complications were analyzed., Results: A total of 100 patients with TSCI were included in the study. The mean age of the patients was 43.4 ± 15.8 in years, with male patients being predominant, at 92%. The most common mechanism of injury was motor vehicular crash, at 68%, followed by fall, at 22%. Most patients, 38%, were graded AIS C, on admission. The most common level of injury was cervical, at 70%. The usual complications recorded were sacral ulcer 28%, and hospital-acquired pneumonia, 20%., Conclusions: TSCI is common in young adult male patients with motor vehicular crash as the mechanism of injury. Most patients in the study had incomplete spinal cord injury (AIS C), with the cervical region as the most common level. The recorded mean length of hospital stay was 1-2 weeks. The most common co-occurring extra spinal injury was traumatic brain injury. At discharge, most developed sacral ulcer and hospital-acquired pneumonia, with stable neurologic status. A multicenter prospective data collection with a larger population and inclusion of more variables are necessary to formulate a regression model and establish the factors that improve the outcomes of TSCI., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Aims: Spinal cord injury (SCI) affects patients' physical, psychological, and social well-being. Presently, treatment modalities for chronic SCI have restricted clinical effectiveness. Mesenchymal stromal cells (MSCs) demonstrate promise in addressing nervous tissue damage. This single-center, open-label, parallel-group randomized clinical trial aimed to assess the safety and efficacy of intraoperative perilesional administration of expanded autologous bone marrow-derived MSCs (BMMSCs), followed by monthly intrathecal injections, in comparison to monthly intrathecal administration of expanded allogeneic umbilical cord-derived MSCs (UCMSCs) for individuals with chronic SCI., Methods: Twenty participants, who had a minimum of 1 year of SCI duration, were enrolled. Each participant in Group A received perilesional BMMSCs, followed by monthly intrathecal BMMSCs for three injections, while Group B received monthly intrathecal UCMSCs for three injections. Safety and efficacy were evaluated using the American Spinal Cord Injury Association (ASIA) score for at least 1 year post the final injection. Statistical analysis was conducted using the Wilcoxon signed-rank test., Results: Group A comprised 11 participants, while Group B included 9. The mean follow-up duration was 22.65 months. Mild short-term adverse events encompassed headaches and back pain, with no instances of long-term adverse events. Both groups demonstrated significant improvements in total ASIA scores, with Group A displaying more pronounced motor improvements., Conclusions: Our findings indicate that perilesional administration of expanded autologous BMMSCs, followed by monthly intrathecal BMMSCs for three injections, or monthly intrathecal UCMSCs for three injections appear to be safe and hold promise for individuals with chronic SCI. Nonetheless, larger-scale clinical trials are imperative to validate these observations., Competing Interests: Declaration of competing interest The authors have no competing interests to disclose., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Spinal cord injury (SCI) is a significant public health issue, leading to physical, psychological, and social complications. Machine learning (ML) algorithms have shown potential in diagnosing and predicting the functional and neurologic outcomes of subjects with SCI. ML algorithms can predict scores for SCI classification systems and accurately predict outcomes by analyzing large amounts of data. This systematic review aimed to examine the performance of ML algorithms for diagnosing and predicting the outcomes of subjects with SCI., Methods: The literature was comprehensively searched for the pertinent studies from inception to May 25, 2023. Therefore, electronic databases of PubMed, Embase, Scopus, and Web of Science were systematically searched with individual search syntax., Results: A total of 9424 individuals diagnosed with SCI across multiple studies were analyzed. Among the 21 studies included, 5 specifically aimed to evaluate diagnostic accuracy, while the remaining 16 focused on exploring prognostic factors or management strategies., Conclusions: ML and deep learning (DL) have shown great potential in various aspects of SCI. ML and DL algorithms have been employed multiple times in predicting and diagnosing patients with SCI. While there are studies on diagnosing acute SCI using DL algorithms, further research is required in this area., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) is associated with substantial healthcare challenges, frequently resulting in enduring sensory and motor deficits alongside various chronic complications. While advanced regenerative therapies have shown promise in preclinical research, their translation into clinical application has been limited. In response, this study utilized a comprehensive network meta-analysis to evaluate the effectiveness of neural stem/progenitor cell (NSPC) transplantation across animal models of SCI. We analyzed 363 outcomes from 55 distinct studies, categorizing the treatments into NSPCs alone (cell only), NSPCs with scaffolds (cell + scaffold), NSPCs with hydrogels (cell + hydrogel), standalone scaffolds (scaffold), standalone hydrogels (hydrogel), and control groups. Our analysis demonstrated significant enhancements in motor recovery, especially in gait function, within the NSPC treatment groups. Notably, the cell only group showed considerable improvements (standardized mean difference [SMD], 2.05; 95 % credible interval [CrI]: 1.08 to 3.10, p < 0.01), as did the cell + scaffold group (SMD, 3.73; 95 % CrI: 2.26 to 5.22, p < 0.001) and the cell + hydrogel group (SMD, 3.37; 95 % CrI: 1.02 to 5.78, p < 0.05) compared to controls. These therapeutic combinations not only reduced lesion cavity size but also enhanced neuronal regeneration, outperforming the cell only treatments. By integrating NSPCs with supportive biomaterials, our findings pave the way for refining these regenerative strategies to optimize their potential in clinical SCI treatment. Although there is no overall violation of consistency, the comparison of effect sizes between individual treatments should be interpreted in light of the inconsistency. STATEMENT OF SIGNIFICANCE: This study presents a comprehensive network meta-analysis exploring the efficacy of neural stem cell (NSC) transplantation, with and without biomaterials, in animal models of spinal cord injury (SCI). We demonstrate that NSCs, particularly when combined with biomaterials like scaffolds or hydrogels, significantly enhance motor and histological recovery post-SCI. These findings underscore the potential of NSC-based therapies, augmented with biomaterials, to advance SCI treatment, offering new insights into regenerative strategies that could significantly impact clinical practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: This review aims to assess the efficacy of transcutaneous electrical nerve stimulation (TENS) for neurogenic bladder after spinal cord injury (SCI)., Materials and Methods: A systematic search was conducted of seven electronic data bases from inception to Dec 31, 2022, to identify randomized controlled trials that studied TENS for neurogenic bladder after SCI. The primary outcomes were maximum cystometric capacity (MCC) and residual urine volume (RUV). Secondary outcomes included maximum detrusor pressure, flow rate, and bladder diary. Random effects models were used in all analyses., Results: Eleven trials involving 881 participants were included. Meta-analysis showed that TENS in addition to conventional treatment had larger MCC (mean difference [MD] 50.55 ml, 95% CI 27.81-73.29, p＜0.0001) and lower RUV (MD -22.96 ml, 95% CI -33.45 to -12.47, p＜0.0001) than did conventional treatment only. Compared with magnetic stimulation, no differences were observed with TENS for MCC (MD -14.49 ml, 95% CI -48.97 to 19.98, p = 0.41) and RUV (MD 25 ml, 95% CI -61.79 to 111.79, p = 0.57). There also were no differences in MCC (MD -7.2 ml, 95% CI -14.56 to 0.16, p= 0.06) and (MD -5.2 ml, 95% CI -60.00 to 49.60, p = 0.851) when compared with solifenacin succinate and pelvic floor biofeedback, respectively., Conclusions: TENS may be an effective treatment option for neurogenic bladder after SCI., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Spinal Cord Injury (SCI) is a condition leading to inflammation, edema, and dysfunction of the spinal cord, most commonly due to trauma, tumor, infection, or vascular disturbance. Symptoms include sensory and motor loss starting at the level of injury; the extent of damage depends on injury severity as detailed in the ASIA score. In the acute setting, maintaining mean arterial pressure (MAP) higher than 85 mmHg for up to 7 days following injury is preferred; although caution must be exercised when using vasopressors such as phenylephrine due to serious side effects such as pulmonary edema and death. Decompression surgery (DS) may theoretically relieve edema and reduce intraspinal pressure, although timing of surgery remains a matter of debate. Methylprednisolone (MP) is currently used due to its ability to reduce inflammation but more recent studies question its clinical benefits, especially with inconsistency in recommending it nationally and internationally. The choice of MP is further complicated by conflicting evidence for optimal timing to initiate treatment, and by the reported observation that higher doses are correlated with increased risk of complications. Thyrotropin-releasing hormone may be beneficial in less severe injuries. Finally, this review discusses many options currently being researched and have shown promising pre-clinical results., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BGD reports the following: receives consulting fees from Clariance, SpineArt, and SpineVision. AHD discloses the following, receives royalties from Spineart and Stryker, consulting fees from Medtornic, research support from Alphatec, Medtronic, and Orthofix, and Fellowship support from Medtronic. The rest of the authors do not report any conflicts., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Female sexual dysfunction (FSD) affects an estimated 40% of women. Unfortunately, FSD is understudied, leading to limited treatment options for FSD. Neuromodulation has shown some success in alleviating FSD symptoms. We developed a pilot study to investigate the short-term effect of electrical stimulation of the dorsal genital nerve and tibial nerve on sexual arousal in healthy women, women with FSD, and women with spinal cord injury (SCI) and FSD., Materials and Methods: This study comprises a randomized crossover design in three groups: women with SCI, women with non-neurogenic FSD, and women without FSD or SCI. The primary outcome measure was change in vaginal pulse amplitude (VPA) from baseline. Secondary outcome measures were changes in subjective arousal, heart rate, and mean arterial pressure from baseline. Participants attended one or two study sessions where they received either transcutaneous dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS). At each session, a vaginal photoplethysmography sensor was used to measure VPA. Participants also rated their level of subjective arousal and were asked to report any pelvic sensations., Results: We found that subjective arousal increased significantly from before to after stimulation in DGNS study sessions across all women. TNS had no effect on subjective arousal. There were significant differences in VPA between baseline and stimulation, baseline and recovery, and stimulation and recovery periods among participants, but there were no trends across groups or stimulation type. Two participants with complete SCIs experienced genital sensations., Conclusions: To our knowledge, this is the first study to measure sexual arousal in response to short-term neuromodulation in women. This study indicates that short-term DGNS but not TNS can increase subjective arousal, but the effect of stimulation on genital arousal is inconclusive. This study provides further support for DGNS as a treatment for FSD., Competing Interests: Conflict of Interest Tim M. Bruns reports serving on the Scientific Advisory Board and received stock options for Stimulai Therapeutics. Priyanka Gupta reports serving on the Medical Advisory Board and received stock options for Stimulai Therapeutics. The remaining authors reported no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Objective: In adults with cervical spinal cord injury (SCI), transcutaneous spinal stimulation (scTS) has improved upper extremity strength and control. This novel noninvasive neurotherapeutic approach combined with training may modulate the inherent developmental plasticity of children with SCI, providing even greater improvements than training or stimulation alone. Because children with SCI represent a vulnerable population, we first must establish the safety and feasibility of any potential novel therapeutic approach. The objectives of this pilot study were to determine the safety, feasibility, and proof of principle of cervical and thoracic scTS for short-term effect on upper extremity strength in children with SCI., Materials and Methods: In this nonrandomized, within-subject repeated measure design, seven participants with chronic cervical SCI performed upper extremity motor tasks without and with cervical (C3-C4 and C6-C7) and thoracic (T10-T11) site scTS. Safety and feasibility of using cervical and thoracic sites scTS were determined by the frequency count of anticipated and unanticipated risks (eg, pain, numbness). Proof-of-principle concept was tested via change in force production during hand motor tasks., Results: All seven participants tolerated cervical and thoracic scTS across the three days, with a wide range of stimulation intensities (cervical sites = 20-70 mA and thoracic site = 25-190 mA). Skin redness at the stimulation sites was observed in four of 21 assessments (19%) and dissipated in a few hours. No episode of autonomic dysreflexia was observed or reported. Hemodynamic parameters (systolic blood pressure and heart rate) remained within stable limits (p > 0.05) throughout the assessment time points at baseline, with scTS, and after the experiment. Hand-grip and wrist-extension strength increased (p < 0.05) with scTS., Conclusions: We indicated that short-term application of scTS via two cervical and one thoracic site is safe and feasible in children with SCI and resulted in immediate improvements in hand-grip and wrist-extension strength in the presence of scTS., Clinical Trial Registration: The Clinicaltrials.gov registration number for the study is NCT04032990., Competing Interests: Conflict of Interest Yury Gerasimenko has a shareholder interest in Onward and Cosyma. He holds certain inventorship rights on intellectual property licensed by the regents of the University of California to NeuroRecovery Technologies and its subsidiaries. The remaining authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Design: Systematic review of the literature., Objectives: In recent years, brain-computer interface (BCI) has emerged as a potential treatment for patients with spinal cord injury (SCI). This is the first systematic review of the literature on invasive closed-loop BCI technologies for the treatment of SCI in humans., Materials and Methods: A comprehensive search of PubMed MEDLINE, Web of Science, and Ovid EMBASE was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: Of 8316 articles collected, 19 studies met all the inclusion criteria. Data from 21 patients were extracted from these studies. All patients sustained a cervical SCI and were treated using either a BCI with intracortical microelectrode arrays (n = 18, 85.7%) or electrocorticography (n = 3, 14.3%). To decode these neural signals, machine learning and statistical models were used: support vector machine in eight patients (38.1%), linear estimator in seven patients (33.3%), Hidden Markov Model in three patients (14.3%), and other in three patients (14.3%). As the outputs, ten patients (47.6%) underwent noninvasive functional electrical stimulation (FES) with a cuff; one (4.8%) had an invasive FES with percutaneous stimulation, and ten (47.6%) used an external device (neuroprosthesis or virtual avatar). Motor function was restored in all patients for each assigned task. Clinical outcome measures were heterogeneous across all studies., Conclusions: Invasive techniques of BCI show promise for the treatment of SCI, but there is currently no technology that can restore complete functional autonomy in patients with SCI. The current techniques and outcomes of BCI vary greatly. Because invasive BCIs are still in the early stages of development, further clinical studies should be conducted to optimize the prognosis for patients with SCI., Competing Interests: Conflict of Interest Alexander G. Weil is a paid consultant for Monteris Medical, Inc and a Clinical Advisory Board member for Synergia. Lior M. Elkaim is an employee with Neuralink. The remaining authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Study Design: This is a report of methods and tools for selection of task and individual configurations targeted for voluntary movement, standing, stepping, blood pressure stabilization, and facilitation of bladder storage and emptying using tonic-interleaved excitation of the lumbosacral spinal cord., Objectives: This study aimed to present strategies used for selection of stimulation parameters for various motor and autonomic functions., Conclusions: Tonic-interleaved functionally focused neuromodulation targets a myriad of consequences from spinal cord injury with surgical implantation of the epidural electrode at a single location. This approach indicates the sophistication of the human spinal cord circuitry and its important role in the regulation of motor and autonomic functions in humans., Competing Interests: Conflict of Interest The authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Motor functional improvement represents a paramount treatment objective in the post-spinal cord injury (SCI) recovery process. However, neuronal cell death and axonal degeneration following SCI disrupt neural signaling, impeding the motor functional recovery. In this study, we developed a multifunctional decellularized spinal cord-derived extracellular matrix (dSECM), crosslinked with glial cell-derived neurotrophic factor (GDNF), to promote differentiation of stem cells into neural-like cells and facilitate axonogenesis and remyelination. After decellularization, the immunogenic cellular components were effectively removed in dSECM, while the crucial protein components were retained which supports stem cells proliferation and differentiation. Furthermore, sustained release of GDNF from the dSECM facilitated axonogenesis and remyelination by activating the PI3K/Akt and MEK/Erk pathways. Our findings demonstrate that the dSECM-GDNF platform promotes neurogenesis, axonogenesis, and remyelination to enhance neural signaling, thereby yielding promising therapeutic effects for motor functional improvement after SCI. STATEMENT OF SIGNIFICANCE: The dSECM promotes the proliferation and differentiation of MSCs or NSCs by retaining proteins associated with positive regulation of neurogenesis and neuronal differentiation, while eliminating proteins related to negative regulation of neurogenesis. After crosslinking, GDNF can be gradually released from the platform, thereby promoting neural differentiation, axonogenesis, and remyelination to enhance neural signaling through activation of the PI3K/Akt and MEK/Erk pathways. In vivo experiments demonstrated that dSECM-GDNF/MSC@GelMA hydrogel exhibited the ability to facilitate neuronal regeneration at 4 weeks post-surgery, while promoting axonogenesis and remyelination at 8 weeks post-surgery, ultimately leading to enhanced motor functional recovery. This study elucidates the ability of neural regeneration strategy to promote motor functional recovery and provides a promising approach for designing multifunctional tissue for SCI treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Neurotrauma is a significant cause of morbidity and mortality in Nigeria. We conducted this systematic review to generate nationally generalizable reference data for the country., Methods: Four research databases and gray literature sources were electronically searched. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Interventions and Cochrane's risk of bias tools. Descriptive analysis, narrative synthesis, and statistical analysis (via paired t-tests and χ 2 independence tests) were performed on relevant article metrics (α = 0.05)., Results: We identified a cohort of 45,763 patients from 254 articles. The overall risk of bias was moderate to high. Most articles employed retrospective cohort study designs (37.4%) and were published during the last 2 decades (81.89%). The cohort's average age was 32.5 years (standard deviation, 20.2) with a gender split of ∼3 males per female. Almost 90% of subjects were diagnosed with traumatic brain injury, with road traffic accidents (68.6%) being the greatest cause. Altered consciousness (48.4%) was the most commonly reported clinical feature. Computed tomography (53.5%) was the most commonly used imaging modality, with skull (25.7%) and vertebral fracture (14.1%) being the most common radiological findings for traumatic brain injury and traumatic spinal injury, respectively. Two-thirds of patients were treated nonoperatively. Outcomes were favorable in 63.7% of traumatic brain injury patients, but in only 20.9% of traumatic spinal injury patients. Pressure sores, infection, and motor deficits were the most commonly reported complications in the latter., Conclusions: This systematic review and pooled analysis demonstrate the significant burden of neurotrauma across Nigeria., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to provide a bibliometric analysis of reported clinical trials of interventional spinal cord injury (SCI) and present the current status, global trends, and scholars' knowledge in this field., Methods: Data were obtained from PubMed and Web of Science (WOS) Core Collection. A literature screening process was conducted to select reports of interventional SCI clinical trials. Qualitative and quantitative analysis was performed based on information from the WOS database. Co-occurrence analysis of keywords, collaboration analysis, and co-citation analysis were performed using VOSviewer., Results: A total of 849 articles were selected for analysis. Therapeutic strategies in the articles were classified into 10 subgroups. Locomotor training, local complication-related treatments, and neuromodulation are the top 3 subgroups. Spinal Cord was the most productive and most frequently cited journal in SCI clinical trials. The most productive country, institution, and author are the United States, the University of Miami, and Harvey LA, respectively. The collaboration network analysis shows that researchers and institutions from the United States, Canada, the United Kingdom, and Australia were the pivotal driving forces in this field. Spinal cord injury, rehabilitation, individuals, electrical stimulation, and exercise are the top 5 most frequent keywords. The co-citation analysis shows that the most frequently cited references are all international standards and guidelines of SCI clinical trials., Conclusions: There is a broad research collaboration network, although it is distributed unevenly worldwide. International standards and guidelines are needed to conduct high-quality clinical trials in the future., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Traumatic spinal cord injury (SCI) may occur across the lifespan and is of global relevance. Damage of the spinal cord results in para- or tetraplegia and is associated with neuropathic pain, spasticity, respiratory, and autonomic dysfunction (i.e., control of bladder-bowel function). While the acute surgical treatment aims at stabilizing the spine and decompressing the damaged spinal cord, SCI patients require neurorehabilitation to restore neural function and to compensate for any impairments including motor disability, pain treatment, and bladder/bowel management. However, the spinal cord has a limited capacity to regenerate and much of the disability may persist, depending on the initial lesion severity and level of injury. For this reason, and the lack of effective drug treatments, there is an emerging interest and urgent need in promoting axonal regeneration and remyelination after SCI through cell- and stem-cell based therapies. This review briefly summarizes the state-of the art management of acute SCI and its neurorehabilitation to critically appraise phase I/II trials from the last two decades that have investigated cell-based therapies (i.e., Schwann cells, macrophages, and olfactory ensheathing cells) and stem cell-based therapies (i.e., neural stem cells, mesenchymal, and hematopoietic stem cells). Recently, two large multicenter trials provided evidence for the safety and feasibility of neural stem cell transplantation into the injured cord, whilst two monocenter trials also showed this to be the case for the transplantation of Schwann cells into the posttraumatic cord cavity. These are milestone studies that will facilitate further interventional trials. However, the clinical adoption of such approaches remains unproven, as there is only limited encouraging data, often in single patients, and no proven trial evidence to support regulatory approval., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background Aims: Exosome therapy for traumatic spinal cord injury (TSCI) is a current research hotspot, but its therapeutic effect and the best source of stem cells for exosomes are unclear., Methods: The Web of Science, PubMed, Embase, Cochrane, and Scopus databases were searched from inception to March 28, 2023. Literature screening, data extraction and risk of bias assessment were performed independently by two investigators., Results: A total of 40 studies were included for data analysis. The findings of our traditional meta-analysis indicate that exosomes derived from stem cells significantly improve the motor function of TSCI at various time points (1 week: weighted mean difference [WMD] = 1.58, 95% confidence interval [CI] 0.87-2.30] 2 weeks: WMD = 3.12, 95% CI 2.64-3.61; 3 weeks: WMD = 4.44, 95% CI 3.27-5.60; 4 weeks: WMD = 4.54, 95% CI 3.42-5.66). Four kinds of stem cell-derived exosomes have been studied: bone marrow mesenchymal stem cells, adipose mesenchymal stem cells, umbilical cord mesenchymal stem cells and neural stem cells. The results of the network meta-analysis showed that there was no significant statistical difference in the therapeutic effect among the exosomes derived from four kinds of stem cells at different treatment time points. Although exosomes derived from bone marrow mesenchymal stem cells are the current research focus, exosomes derived from neural stem cells have the most therapeutic potential and should become the focus of future attention., Conclusions: The exosomes derived from stem cells can significantly improve the motor function of TSCI rats, and the exosomes derived from neural stem cells have the most therapeutic potential. However, the lower evidence quality of animal studies limits the reliability of experimental results, emphasizing the need for more high-quality, direct comparative studies to explore the therapeutic efficacy of exosomes and the best source of stem cells., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) is a matter of significant clinical concern, often treated through early surgical decompression along with methylprednisolone sodium succinate (MPSS). However, the side effects and the unsatisfactory focal concentration of MPSS have limited its further applications. To address this limitation, herein, a versatile drug delivery system of zeolitic imidazole framework-8 (ZIF-8) and gelatin methacryloyl microneedles (GelMA MNs) was developed for stable, transdural, and controlled sustained release of drugs in SCI. The microneedles were used to create tiny pores in the dura mater, allowing for the direct administration of drugs into the spinal cord. ZIF-8 provided a secondary extended release once they were separated from the microneedles. To attenuate the neuroinflammation, MPSS was selected. Such a combination of ZIF-8 and GelMA MNs was able to prolong the release period of MPSS to five days. The system showed transdural capacity, reduction of M 1 polarization, and decrease in NLRP3-positive inflammasome and proinflammatory cytokines. In vivo studies indicated that this novel drug delivery strategy could constrict the inflammatory microenvironment, reduce glial scar formation, and promote neural regeneration. Thus, this versatile drug delivery system provides an up-and-coming alternative for stable, transdural, and controlled sustained release of drugs to those suffering from SCI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Spinal cord injury (SCI) is a devastating condition, often leading to significant disability and impairment. As crucial immune cells, macrophages play a critical role in the pathophysiology of SCI. Understanding the current state of knowledge and research trends related to macrophages in SCI is crucial for developing effective therapeutic interventions., Methods: Using search strategies, we retrieved relevant articles from the Web of Science Core Collection (WOSCC), resulting in a robust dataset for analysis. VOSviewer, Citespace, and PRISM were employed for analysis and visualization. Various bibliometric indicators, including publication trends, citation analysis, co-authorship networks, and keyword analysis, were utilized to assess the scholarly landscape of macrophage research in SCI., Results: Our findings revealed a steady increase in publications over the past 33 years, indicating a growing interest in this field. We identified Popovich Phillip G was the most influential author, Ohio State University was the most influential institution, and identification of 2 distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord was the most influential paper in this field., Conclusions: This bibliometric analysis provides a comprehensive overview of the current knowledge landscape and research trends regarding macrophages in SCI. Neuroinflammation and macrophage polarization, transplation and molecular mechanism were emerging research areas and novel directions. Our study serves as a valuable resource for researchers in spinal cord injury research and therapeutic development., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) can lead to the loss of motor, sensory, or autonomic function due to neuronal death. Unfortunately, the adult mammalian spinal cord has limited intrinsic regenerative capacity, making it difficult to rebuild the neural circuits necessary for functional recovery. However, recent evidence suggests that in vivo fate reprogramming of resident cells that are normally non-neurogenic can generate new neurons. This process also improves the pathological microenvironment, and the new neurons can integrate into the local neural network, resulting in better functional outcomes in SCI animal models. In this concise review, we focus on recent advances while also discussing the challenges, pitfalls, and opportunities in the field of in vivo cell fate reprogramming for spinal cord repair., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Epidural spinal cord stimulation (eSCS) has shown promise for restoring some volitional motor control after spinal cord injury (SCI). Maximizing therapeutic response requires effective spatial stimulation generated through careful configuration of anodes and cathodes on the eSCS lead. By exploring the way the spatial distribution of low frequency stimulation affects muscle activation patterns, we investigated the spatial specificity of stimulation-evoked responses for targeted muscle groups for restoration after chronic SCI (cSCI) in participants in the Epidural Stimulation After Neurologic Damage (E-STAND) trial., Materials and Methods: Fifteen participants with Abbreviated Injury Scale A cSCI from the E-STAND study were evaluated with a wide range of bipolar spatial patterns. Surface electromyography captured stimulation-evoked responses from the rectus abdominis (RA), intercostal, paraspinal, iliopsoas, rectus femoris (RF), tibialis anterior (TA), extensor hallucis longus (EHL), and gastrocnemius muscle groups bilaterally. Peak-to-peak amplitudes were analyzed for each pulse across muscles. Stimulation patterns with dipoles parallel (vertical configurations), perpendicular (horizontal configurations), and oblique (diagonal configurations) relative to the rostral-caudal axis were evaluated., Results: Cathodic stimulation in the transverse plane indicated ipsilaterally biased activation in RA, intercostal, paraspinal, iliopsoas, RF, TA, EHL, and gastrocnemius muscles (p < 0.05). We found that caudal cathodic stimulation was significantly more activating only in the RF and EHL muscle groups than in the rostral (p < 0.037 and p < 0.006, respectively). Oblique stimulation was found to be more activating in the RA, intercostal, paraspinal, iliopsoas, and TA muscle groups than in the transverse (p < 0.05)., Conclusions: Cathodic stimulation provides uniform specificity for targeting laterality. Few muscle groups responded specifically to variation in rostral/caudal stimulation, and oblique stimulation improved stimulation responses when compared with horizontal configurations. These relations may enable tailored targeting of muscle groups, but the surprising amount of variation observed suggests that monitoring these evoked muscle responses will play a key role in this tailoring process., Clinical Trial Registration: The Clinicaltrials.gov registration number for the study is NCT03026816., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to investigate the effect of microRNA 146a (miR-146a) overexpressed bone marrow mesenchymal stem cells (BMMSCs) exosomes on spinal cord injury (SCI) recovery., Methods: Rat BMMSCs were isolated and transfected with miR-146a mimic (miR-mimic) and control mimic (NC-mimic), after which their exosomes were isolated. Afterward, SCI rat models were constructed, then treated with phosphate buffer saline (PBS), NC BMMSCs exosomes (separated from the culture medium of BMMSCs with NC-mimic), and miR-146a overexpressed BMMSCs exosomes (isolated from the culture medium of BMMSCs with miR-mimic), respectively; additionally, rats underwent sham surgery were treated with PBS as controls., Results: MiR-146a was upregulated in BMMSCs, and BMMSCs derived exosomes post miR-mimic transfection. Then in SCI rats, BMMSCs exosomes elevated the Basso, Beattie, and Bresnahan (BBB) score and reduced hematoxylin&eosin-reflected spinal cord tissue injury. In addition, BMMSCs exosomes did not affect TUNEL positive cells rate while increased NeuN(+) cells/field in spinal cord tissue from SCI rats. As for inflammation, BMMSCs exosomes repressed pro-inflammatory cytokine expressions, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, in spinal cord tissue from SCI rats. Furthermore, miR-146a overexpressed BMMSCs exosomes presented with notably better effects regarding elevating BBB score in SCI rats and reducing tissue injury, neuron apoptosis, and inflammation while enhancing neuron viability in spinal cord tissue from SCI rats., Conclusions: MiR-146a overexpressed BMMSCs exosomes enhance locomotor capacity and neuron viability while reducing neuron apoptosis and spinal cord tissue inflammation in SCI rats., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Bio-factor stimulation is essential for axonal regeneration in the central nervous system. Thus, persistent and efficient factor delivery in the local microenvironment is an ideal strategy for spinal cord injury repair. We developed a biomimetic hydrogel scaffold to load biofactors in situ and release them in a controlled way as a promising therapeutic modality. Hyaluronic acid and silk fibroin were cross-linked as the basement of the scaffolds, and poly-dopamine coating was used to further increase the loading of factors and endow the hydrogel scaffolds with ideal physical and chemical properties and proper biocompatibility. Notably, neurotrophin-3 release from the hydrogel scaffolds was prolonged to 28 days. A spinal cord injury model was constructed for hydrogel scaffold transplantation. After eight weeks, significant NF200-positive nerve fibers were observed extending across the glial scar to the center of the injured area. Due to the release of neurotrophin-3, spinal cord regeneration was enhanced, and the cavity area of the injury graft site and inflammation associated with CD68 positive cells were reduced, which led to a significant improvement in hind limb motor function. The results show that the hyaluronic acid/silk fibroin/poly-dopamine-coated biomimetic hydrogel scaffold achieved locally slow release of neurotrophin-3, thus facilitating the regeneration of injured spinal cord. STATEMENT OF SIGNIFICANCE: Hydrogels have received great attention in spinal cord regeneration. Current research has focused on more efficient and controlled release of bio-factors. Here, we adopted a mussel-inspired strategy to functionalize the hyaluronic acid/silk fibroin hydrogel scaffold to increase the load of neurotrophin-3 and extend the release time. The hydrogel scaffolds have ideal physiochemical properties, proper release rate, and biocompatibility. Owing to the continuous neurotrophin-3 release from implanted scaffolds, cavity formation is reduced, inflammation alleviated, and spinal cord regeneration enhanced, indicating great potential for bio-factor delivery in soft tissue regeneration applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Spinal cord injury (SCI) treatment is still a challenge and new treatments that help these patients are being considered. Recent studies showed that the use of self-assembled peptide (SAP) can be useful in SCI treatment., Materials and Methods: In this meta-analysis, we investigated the effect of SAP administration on locomotion recovery after SCI. Records were obtained from a comprehensive search of data bases. Articles were scrutinized for inclusion and exclusion criteria. Data were analyzed and results were reported as standardized mean difference (SMD) with 95% CI. Subgroup analysis was also performed., Results: A total of 14 studies and 17 separate experiments were included in the final analysis. Treatment with SAP structures after SCI resulted in a significant improvement in animal motor function (SMD = 1.13; 95% CI: 0.68-1.58; p < 0.0001). SAP treatment facilitated axon sprouting (SMD = 0.76; 95% CI: 0.33-1.18; p < 0.0001) and reduction of glial scar (SMD = -1.02; 95% CI: -1.94 to -0.09; p = 0.03). The difference in SAP type, its concentration, follow-up time, and SCI model had no effect on SAP effectiveness. In addition, SAP administration had a similar effect on improving locomotion in all three immediate, acute, and subacute phases which gives the good news of using this treatment for patients who are in the chronic phase., Conclusion: SAP treatment can be considered as a potential treatment to help the motor recovery of SCI and axon regeneration., (Copyright © 2022 International Neuromodulation Society. All rights reserved.)

Objective: To evaluate the effects of exercise training on neurological recovery, Growth Transforming Factor-β1 (TGF-β1), Hypoxia Inducible Factor-1α (HIF-1α), and Nogo-NgR signaling pathways after spinal cord injury in rats., Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: normal group, sham-operated group, model group, and training group. The rat spinal cord injury model was established using Allen's method, and the training group received exercise training on the 8th day postoperatively. The Basso, Beattie and Bresnahan (BBB) score, modified Tarlow score, and inclined plane test scores were compared in each group before injury and 1, 7, 14, 21 and 28 days after injury., Results: The BBB score and modified Tarlow score of the model group and the training group were 0 at the first day after the injury, and gradually increased on the seventh day onwards (p < 0.05). The BBB score and modified Tarlow score of the training group were higher than those of the model group at the 14th, 21st and 28th day (p < 0.05). The angles of the inclined plate at multiple time points after injury were lower in the model group and the training group than in the normal group and the sham-operated group (p < 0.05); The angles of the inclined plate at the 14th, 21st and 28th day after injury were higher in the training group than in the model group (p < 0.05)., Conclusion: The mechanism of exercise training may be connected to the inhibition of the Nogo-NgR signaling pathway to promote neuronal growth., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: This review investigated the effectiveness of behaviour-change interventions to improve physical activity (PA) participation in individuals with a spinal cord injury. Additionally, the review sought to analyse the change in PA behaviour that might be expected by utilising behaviour change in PA interventions and what specific intervention characteristics, application of behaviour change theories, and behaviour change techniques are most efficacious., Methods: The protocol was prospectively registered on PROSPERO: CRD42021252744, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed in this review. Eight databases were comprehensively searched using a well-defined strategy developed in collaboration with an academic liaison librarian. Randomised, non-randomised controlled, and non-controlled studies were included in this review; however, controlled and non-controlled studies were analysed separately. Studies were included if participants were older than 16 years and had an SCI of any cause, level or severity, regardless of the time since injury. The behaviour change technique taxonomy version 1 was used to code the intervention characteristics for behaviour modification. The combined effects across studies were pooled in a meta-analysis, and the risk of bias was assessed using the Cochrane Risk of Bias 2 tool., Results: The search retrieved 10,155 titles and abstracts. After duplicate removal and screening against the eligibility criteria, 23 studies were included. The overall effect estimate of the change in PA participation in the controlled trials post-intervention was medium (d = 0.50, 95% CI = 0.31-0.70) in favour of behaviour-targeted interventions. The mean difference in PA volume between pre- and post-intervention was an increase of 22 minutes per week (95% CI = 5.96-38.90). Interventions that provided practical support (d = 0.81, 95% CI = 0.46-1.16), which were individualised (d = 0.62, 95% CI = 0.34-0.90) and that utilised monitoring (d = 0.59, 95% CI = 0.34-0.83) had a greater effect on change to PA than those that were group-based and did not utilise those specific techniques., Conclusions: Interventions that target behaviour change to increase PA in people with SCI appear effective. Utilising behaviour change frameworks and specific behaviour change techniques augments PA uptake and levels, and interventions aimed at improving PA in people with SCI should incorporate a behaviour modification component. More research is needed on the isolated effect of intervention structure parameters and specific behaviour change techniques., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Recent studies using epidural spinal cord stimulation (SCS) have demonstrated restoration of motor function in individuals previously diagnosed with chronic spinal cord injury (SCI). In parallel, the spinal evoked compound action potentials (ECAPs) induced by SCS have been used to gain insight into the mechanisms of SCS-based chronic pain therapy and to titrate closed-loop delivery of stimulation. However, the previous characterization of ECAPs recorded during SCS was performed with one-dimensional, cylindrical electrode leads. Herein, we describe the unique spatiotemporal distribution of ECAPs induced by SCS across the medial-lateral and rostral-caudal axes of the spinal cord, and their relationship to polysynaptic lower-extremity motor activation., Materials and Methods: In each of four sheep, two 24-contact epidural SCS arrays were placed on the lumbosacral spinal cord, spanning the L3 to L6 vertebrae. Spinal ECAPs were recorded during SCS from nonstimulating contacts of the epidural arrays, which were synchronized to bilateral electromyography (EMG) recordings from six back and lower-extremity muscles., Results: We observed a triphasic P1, N1, P2 peak morphology and propagation in the ECAPs during midline and lateral stimulation. Distinct regions of lateral stimulation resulted in simultaneously increased ECAP and EMG responses compared with stimulation at adjacent lateral contacts. Although EMG responses decreased during repetitive stimulation bursts, spinal ECAP amplitude did not significantly change. Both spinal ECAP responses and EMG responses demonstrated preferential ipsilateral recruitment during lateral stimulation compared with midline stimulation. Furthermore, EMG responses were correlated with stimulation that resulted in increased ECAP amplitude on the ipsilateral side of the electrode array., Conclusions: These results suggest that ECAPs can be used to investigate the effects of SCS on spinal sensorimotor networks and to inform stimulation strategies that optimize the clinical benefit of SCS in the context of managing chronic pain and the restoration of sensorimotor function after SCI., (Published by Elsevier Inc.)

Background Aims: Several studies have reported that mesenchymal stromal cells (MSCs) may improve neurological functions in patients with spinal cord injury (SCI). In this study, we conducted a systematic review and meta-analysis to summarize the effects of MSC treatment on different degrees of severity of SCI., Methods: Systematic searching of studies reporting outcomes of MSCs on specific injury severities of patients with SCI was performed in The National Library of Medicine (MEDLINE), Embase and Cochrane for published articles up to the 6 July 2022. Two investigators independently reviewed the included studies and extracted the relevant data. The standardized mean differences of American Spinal Injury Association (ASIA) motor score, ASIA light touch scores, ASIA pinprick scores and the Barthel index between baseline and follow-ups were pooled., Results: A total of eight studies were included. A large majority focused on patients with ASIA grade A classification. The pooled mean differences of ASIA motor scores, ASIA light touch scores, ASIA pinprick scores and the Barthel index were -2.78 (95% confidence interval [CI] -5.12 to -0.43, P = 0.02), -18.26 (95% CI -26.09 to -10.43, P < 0.01), -17.08 (95% CI -24.10 to -10.07, P < 0.01) and -4.37 (95% CI -10.96 to 2.22, P = 0.19), respectively., Conclusions: MSC transplantation was a significantly effective therapy for patients with SCI with ASIA grade A. In the future, further studies are warranted to confirm the potential beneficial effects of MSC therapy., Competing Interests: Declaration of Competing Interest CM, XW, WL, ZL, NL and YSX are the employees of Everunion Biotechnology Co. Ltd., Tianjin., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Transplantation of allogeneic adult spinal cord tissues (aSCTs) to replace the injured spinal cord, serves as a promising strategy in complete spinal cord injury (SCI) repair. However, in addition to allograft immune rejection, damage-associated molecular pattern (DAMP)-mediated inflammatory microenvironments greatly impair the survival and function of transplants. In this study, we aimed to regulate the immune microenvironment after aSCT implantation by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects. The F-G/H hydrogel exhibited the capacities of DAMP scavenging, sustainably released anti-inflammatory cytokines, and reduced lymphocyte accumulation, thereby modulating the immune response and enhancing the survival and function of aSCTs. When the hydrogel was used in combination with a systemic immunosuppressive drug treatment, the locomotor functions of SCI rats were significantly improved after aSCTs and F-G/H transplantation. This biomaterial-based immunomodulatory strategy may provide the potential for spinal cord graft replacement for treating SCI. STATEMENT OF SIGNIFICANCE: In this study, we aimed to regulate the immune microenvironment by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects. We found that with the treatment of F-G/H hydrogel, the aSCT survival and function was significantly improved, as a result of reducing recruitment and activation of immune cells through TLR- and ST-2- related signaling. With the combination of immunosuppressive drug treatment, the locomotor functions of SCI rats were significantly improved after aSCTs and F-G/H transplantation. Findings from this work suggest the potential application of the F-G/H as a biomaterial-based immunoregulatory strategy for improving the therapeutic efficiency of the transplanted spinal cord graft for spinal cord injury repair., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Spinal cord injury (SCI), a debilitating medical condition that can cause irreversible loss of neurons and permanent paralysis, currently has no cure. However, regenerative medicine may offer a promising treatment. Given that numerous regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding and characterising the mechanical properties of the spinal cord tissue is very important. In this study, we have systematically characterised the spatiotemporal changes in elastic stiffness (elastic modulus, Pa) and viscosity (drop in peak force, %) of injured rat thoracic spinal cord tissues at distinct time points after crush injury using the indentation technique. Our results demonstrate that in comparison with uninjured spinal cord tissue, the injured tissues exhibited lower stiffness (median 3281 Pa versus 9632 Pa; P < 0.001) but demonstrated elevated viscosity (median 80% versus 57%; P < 0.001) at 3 days postinjury. Between 4 and 6 weeks after SCI, the overall viscoelastic properties of injured tissues returned to baseline values. At 12 weeks after SCI, in comparison with uninjured tissue, the injured spinal cord tissues displayed a significant increase in both elasticity (median 13698 Pa versus 9920 Pa; P < 0.001) and viscosity (median 64% versus 58%; P < 0.001). This work constitutes the first quantitative mapping of spatiotemporal changes in spinal cord tissue elasticity and viscosity in injured rats, providing a mechanical basis of the tissue for future studies on the development of biomaterials for SCI repair. STATEMENT OF SIGNIFICANCE: Spinal cord injury (SCI) is a devastating disease often leading to permanent paralysis. While enormous progress in understanding the molecular pathomechanisms of SCI has been made, the mechanical properties of injured spinal cord tissue have received considerably less attention. This study provides systematic characterization of the biomechanical evolution of rat spinal cord tissue after SCI using a microindentation test method. We find spinal cord tissue behaves significantly softer but more viscous immediately postinjury. As time passes, the lesion site gradually returns to baseline values and then displays pronounced increased viscoelastic properties. As host tissue mechanical properties are a crucial consideration for any biomaterial implanted into central nervous system, our results may have important implications for further studies of SCI repair., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Study Design: Prospective observational cohort study linked with administrative data., Objectives: Magnetic Resonance Imaging (MRI) is routinely performed after traumatic spinal cord injury (TSCI), facilitating early, accurate diagnosis to optimize clinical management. Prognosis from early MRI post-injury remains unclear, yet if available could guide early intervention. The aim of this study was to determine the association of spinal cord intramedullary haematoma and/or extent of cord compression evident on initial spine MRI with neurological grade change after TSCI., Methods: Individuals with acute TSCI ≥16 years of age; MRI review. Neurological gradings (American Spinal Injury Association Impairment Scale (AIS)) were compared with initial MRI findings. Various MRI parameters were evaluated for prediction of neurological improvement pre-discharge., Results: 120 subjects; 79% male, mean (SD) age 51.0 (17.7) years. Motor vehicle crashes (42.5%) and falls (40.0%) were the most common injury mechanisms. Intramedullary spinal cord haematoma was identified by MRI in 40.0% of patients and was associated with more severe neurologic injury (58.3% initially AIS A). Generalised linear regression showed higher maximum spinal cord compression (MSCC) was associated with lower likelihood of neurological improvement from initial assessment to follow up prior to rehabilitation discharge. Combined thoracic level injury, intramedullary haematoma, and MSCC > 25% resulted in almost 90% probability of pre-discharge AIS (grade A) remaining unchanged from admission assessment., Conclusions: MRI is a vital tool for evaluating the severity and extent of TSCI, assisting in appropriate management decision-making early in TSCI patient care. This study adds to the body of knowledge assisting clinicians in prognostication., Competing Interests: Declaration of Competing Interest The Authors declares that there are no competing interests for any of them., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background Aims: To explore the optimal transplantation strategy of bone marrow mesenchymal stem cells in subacute traumatic spinal cord injury in animal experiments in order to provide reference for future animal studies and clinical research., Methods: The PubMed, Embase and Web of Science databases were systematically searched (inception to January 4, 2022). Literature search, data extraction and bias assessment were performed by two independent reviewers., Results: A total of 50 articles were included for analysis. Results of both traditional meta-analysis and network meta-analysis showed that high-dose (≥1 × 10 6 ) transplantation was significantly better than low-dose (<1 × 10 6 ) transplantation and intralesional transplantation was significantly better than intravenous transplantation., Conclusions: Given the limited quality of evidence from current animal studies, more high-quality head-to-head comparisons are needed in the future to delve into the optimal transplantation strategy for stem cells., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: This scoping review was undertaken to synthetize and appraise the literature on the potential mechanisms of action of functional electrical stimulation therapy in combination with task-specific training (FEST + TST) in the rehabilitation following stroke, spinal cord injury, traumatic brain injury, or multiple sclerosis., Materials and Methods: The literature search was performed using multiple databases (including APA, PsycInfo, Medline, PubMed, EMBASE, CCRCT, and Cochrane Database of Systematic Reviews) from 1946 to June 2020. The literature search used the following terms: (spinal cord injury, paraplegia, tetraplegia, quadriplegia, stroke, multiple sclerosis, traumatic brain injury, or acquired brain injury) AND (functional electrical stimulation or FES). The search included clinical and preclinical studies without limits to language., Results: Of the 8209 titles retrieved from the primary search, 57 publications fulfilled the inclusion and exclusion criteria for this scoping review. While most publications were clinical studies (n = 50), there were only seven preclinical studies using animal models. The results of this review suggest that FEST + TST can result in multiple effects on different elements from the muscle to the cerebral cortex. However, most studies were focused on the muscle changes after FEST + TST., Conclusions: The results of this scoping review suggest that FEST + TST can result in multiple effects on different elements of the neuromuscular system, while most research studies were focused on the muscle changes after FEST + TST. Despite the efficacy of the FEST + TST in the neurorehabilitation after CNS injury or disease, the results of this review underline an important knowledge gap with regards to the actual mechanism of action of FEST + TST., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Nerve implants functionalized with growth factors and stem cells are critical to promote neurite outgrowth, regulate neurodifferentiation, and facilitate nerve regeneration. In this study, human umbilical cord mesenchymal stem cells (hUCMSCs) and 3,4-hydroxyphenalyalanine (DOPA)-containing insulin-like growth factor 1 (DOPA-IGF-1) were simultaneously applied to enhance the bioactivity of poly(lactide-co-glycolide) (PLGA) substrates which will be potentially utilized as nerve implants. In vitro and in vivo evaluations indicated that hUCMSCs and DOPA-IGF-1 could synergistically regulate neurite outgrowth of PC12 cells, improve intravital recovery of motor functions, and promote conduction of nerve electrical signals in vivo. The enhanced functional and structural nerve regeneration of injured spinal cord might be mainly attributable to the synergistically enhanced biofunctionality of hUCMSCs and DOPA-IGF-1/PLGA on the bioactive interfaces. Findings from this study demonstrate the potential of hUCMSC-seeded, DOPA-IGF-1-modified PLGA implants as promising candidates for promoting axonal regeneration and motor functional recovery in spinal cord injury treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to identify factors associated with the intensive care unit (ICU) length of stay (LOS) of patients with an acute traumatic spinal cord injury above T6., Methods: We performed a retrospective, observational study of patients admitted to an ICU between 1998 and 2017 (n = 241). The LOS was calculated using a cumulative incidence function, with events of death being considered a competing event. Factors associated with the LOS were analyzed using both a cause-specific Cox proportional hazards regression model and a competing risk model. A multistate approach was also used to analyze the impact of nosocomial infections on the LOS., Results: A total of 211 patients (87.5%) were discharged alive from the ICU (median LOS = 23 days), and 30 (12.4%) died (median LOS = 11 days). In the multivariate analysis after adjusting for variables collected 4 days after the ICU admission, a higher American Spinal Injury Association motor score (subdistribution hazards ratio [sHR] = 1.01), neurological level C5-C8 (HR = 0,64), and lower Sequential Organ Failure Assessment score (sHR = 0.82) and fluid balance (sHR = 0.95) on day 4 were linked to a lower LOS in this unit. In the multivariate analysis, the onset of an infection was significantly associated with a longer LOS when adjusting for variables collected both at ICU admission (adjusted sHR = 0.62; 95% confidence interval = 0.50-0.77) and on day 4 (adjusted hazards ratio = 0.65; 95% confidence interval = 0.52-0.80)., Conclusions: After adjusting the data for conventional variables, we identified a lower American Spinal Injury Association motor score, injury level C5-C8, a higher Sequential Organ Failure Assessment score on day 4, a more positive fluid balance on day 4, and the onset of an infection as factors independently associated with a longer ICU LOS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Numerous preclinical studies have been performed in recent years on the effects of the administration of growth factor gene-modified cells in spinal cord injury (SCI). However, findings of these studies are contradictory., Objective: The present study aims to conduct a systematic review and meta-analysis of animal studies evaluating the effects of administration of growth factor gene-modified cells on locomotion recovery after SCI., Methods: A search of the MEDLINE, Embase, Scopus, and Web of Science databases was conducted, including all animal studies until the end of 2020. Two researchers screened search results, summarized relevant studies and assessed risk of bias, independently., Results: Thirty-three studies were included in the final analysis. Transplantation of growth factor gene-modified cells in the injured spinal cord resulted in a significant improvement in locomotion of animals compared with nontreated animals (standardized mean difference = 1.86; 95% confidence interval, 1.39-2.33; P < 0.0001)] and non-genetically modified cell-treated animals (standardized mean difference = 1.30; 95% confidence interval, 0.80-1.79; P < 0.0001). Transplantation efficacy of these cells failed to achieve significance in moderate lesions (P = 0.091), when using modified neural stem/progenitor cells (P = 0.164), when using synthetic neurotrophins (P = 0.086) and when the number of transplanted cells was less than 1.0 × 10 5 cells per animal (P = 0.119)., Conclusions: The results showed that transplantation of growth factor gene- modified cells significantly improved locomotion in SCI animal models. However, there is a major concern regarding the safety of transplantation of genetically modified cells, in terms of overexpressing growth factors. Further studies are needed before any effort to perform a translational and clinical study., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To examine how the quality of spinal cord injury peer mentorship relationships and mentor-mentee behaviors are impacted by interaction modality., Methods: Using a within-subjects, repeated measures, experimental design, peer mentors (n = 8) completed two mentoring sessions with a standardized mentee in a telephone and a video chat condition. Measures of therapeutic alliance and autonomy supportiveness were administered following each session. Mentors' leadership behaviors, motivational interviewing skills, and behavior change techniques were compared across conditions. Mentors' and mentees' use of motivational interviewing skills and behavior change techniques were further analyzed using state space grids., Results: Mentors' therapeutic alliance, autonomy supportiveness, use of leadership behaviors, motivational interviewing skills, and behavior change techniques did not significantly differ across the two conditions (ps > 0.123; Cohen's d range = 0.218-0.619). State space grids analyses revealed that the dynamic structure of mentoring conversations was similar when interactions occurred through the telephone versus video chat., Conclusions: Mentors were effective at forming positive, autonomy supportive relationships with mentees in telephone and video chat interaction conditions. Mentors also used leadership/counselling behaviors to a similar extent when interacting through these two modalities., Practice Implications: Organizations that provide peer mentorship can have confidence in using both telephone and video chat modalitites., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Because full functional recovery after spinal cord injury (SCI) remains a major challenge, stem cell therapies represent promising strategies to improve neurologic functions after SCI. The olfactory mucosa (OM) displays an attractive source of multipotent cells for regenerative approaches and is easily accessible by biopsies because of its exposed location. The regenerative capacity of the resident olfactory stem cells (OSCs) has been demonstrated in animal as well as clinical studies. This study aims to demonstrate the feasibility of isolation, purification and cultivation of OSCs., Methods: OM specimens were taken dorso-posterior from nasal middle turbinate. OSCs were isolated and purified using the neurosphere assay. Differentiation capacity of the OSCs in neural lineage and their behavior in a plasma clot matrix were investigated., Results: Our study demonstrated that OSCs differentiated into neural lineage and were positive for GFAP as well as β-III tubulin. Furthermore, OSCs were viable and proliferated in a plasma clot matrix., Conclusions: Because there are no standard methods for purification, characterization, and delivery of OSCs to the injury site, which is a prerequisite for the clinical approval, this study focuses on the establishment of appropriate methods and underlines the high potential of the OM for autologous cell therapeutic approaches., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Phase 1 of the SUBSCI I/IIa (Systemic Umbilical Cord Blood Administration in Patients with Acute Severe Contusion Spinal Cord Injury) study focused on safety and primary efficacy of multiple systemic infusions of allogeneic unrelated human umbilical cord blood mononuclear cells in patients with severe acute spinal cord contusion having severe neurologic deficit. The primary end point was safety. The secondary end point was the restoration of motor and sensory function in lower limbs within a 1-year period., Methods: Ten patients with acute contusion spinal cord injury (SCI) and American Spinal Injury Association (ASIA) level A/B deficit were enrolled into phase 1. Patients were treated with 4 infusions of group-matched and rhesus-matched cord blood samples after primary surgery within 3 days after SCI. All patients were followed up for 12 months after SCI. Safety was assessed using adverse events classification depending on severity and relation to cell therapy. Primary efficacy was assessed using dynamics of deficit (ASIA scale)., Results: The overall number of adverse events reached 419 in 10 patients. Only 2 were estimated as possibly related to cell therapy, and the remaining 417 were definitely unrelated. Both adverse events were mild and clinically insignificant. No signs of immunization were found in participants. Analysis of clinical outcomes also showed that cell therapy promotes significant functional restoration of motor function., Conclusions: The data obtained suggest that systemic administration of allogeneic, non-human leukocyte antigen-matched human umbilical cord blood is safe and shows primary efficacy in adults with severe acute contusion SCI and ASIA level A/B deficit., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The individual approaches of regenerative medicine efforts alone and rehabilitation efforts alone have not yet fully restored function after severe spinal cord injury (SCI). Regenerative rehabilitation may be leveraged to promote regeneration of the spinal cord tissue, and promote reorganization of the regenerated neural pathways and intact spinal circuits for better functional recovery for SCI. Conductive biomaterials may be a linchpin that empowers the synergy between regenerative medicine and rehabilitation approaches, as electrical stimulation applied to the spinal cord could facilitate neural reorganization. In this review, we discuss current regenerative medicine approaches in clinical trials and the rehabilitation, or neuromodulation, approaches for SCI, along with their respective translational limitations. Furthermore, we review the translational potential, in a surgical context, of conductive biomaterials (e.g., conductive polymers, carbon-based materials, metallic nanoparticle-based materials) as they pertain to SCI. While pre-formed scaffolds may be difficult to translate to human contusion SCIs, injectable composites that contain blended conductive components and can form within the injury may be more translational. However, given that there are currently no in vivo SCI studies that evaluated conductive materials combined with rehabilitation approaches, we discuss several limitations of conductive biomaterials, including demonstrating safety and efficacy, that will need to be addressed in the future for conductive biomaterials to become SCI therapeutics. Even so, the use of conductive biomaterials creates a synergistic opportunity to merge the fields of regenerative medicine and rehabilitation and redefine what regenerative rehabilitation means for the spinal cord. STATEMENT OF SIGNIFICANCE: For spinal cord injury (SCI), the individual approaches of regenerative medicine and rehabilitation are insufficient to fully restore functional recovery; however, the goal of regenerative rehabilitation is to combine these two disparate fields to maximize the functional outcomes. Concepts similar to regenerative rehabilitation for SCI have been discussed in several reviews, but for the first time, this review considers how conductive biomaterials may synergize the two approaches. We cover current regenerative medicine and rehabilitation approaches for SCI, and the translational advantages and disadvantages, in a surgical context, of conductive biomaterials used in biomedical applications that may be additionally applied to SCI. Furthermore, we identify the current limitations and translational challenges for conductive biomaterials before they may become therapeutics for SCI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: The spinal cord injury (SCI) patient population is overwhelmingly affected by neuropathic pain (NP), a secondary condition for which therapeutic options are limited and have a low degree of efficacy. The objective of this study was to identify novel deep brain stimulation (DBS) targets that may theoretically benefit those with NP in the SCI patient population. We hypothesize that localized changes in white matter identified in SCI subjects with NP compared to those without NP could be used to develop an evidence-based approach to DBS target identification., Materials and Methods: To classify localized neurostructural changes associated with NP in the SCI population, we compared white matter fiber density (FD) and cross section (FC) between SCI subjects with NP (n = 17) and SCI subjects without NP (n = 15) using diffusion-weighted magnetic resonance imaging (MRI). We then identified theoretical target locations for DBS using fiber bundles connected to significantly altered regions of white matter. Finally, we used computational models of DBS to determine if our theoretical target locations could be used to feasibly activate our fiber bundles of interest., Results: We identified significant increases in FC in the splenium of the corpus callosum in pain subjects when compared to controls. We then isolated five fiber bundles that were directly connected to the affected region of white matter. Our models were able to predict that our fiber bundles of interest can be feasibly activated with DBS at reasonable stimulation amplitudes and with clinically relevant implantation approaches., Conclusions: Altogether, we identified neuroarchitectural changes associated with NP in the SCI cohort and implemented a novel evidence-driven target selection approach for DBS to guide future research in neuromodulation treatment of NP after SCI., (Copyright © 2021. Published by Elsevier Inc.)

Spinal cord injury is a significant public health issue with high psychological and financial costs to both the family and the society. Effective treatment strategies are hence of immense value. Several reports have suggested application of amniotic membrane for treating injuries, and there is evidence that it may be used to treat spinal injuries. In this animal model study, we explore biochemical changes in amniotic membrane treated injured spinal cord with respect to untreated injured and uninjured spinal cord using Raman spectroscopy. Multivariate statistical analysis is able to classify control, untreated, and treated with 92%, 87%, and 80% efficiency, respectively; suggesting unique biochemical changes in each group. Such studies may lead to development of minimally invasive methodologies for spinal cord injury treatment monitoring., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)