Restoration Of Motor Function Research Articles

Efficacy of growth factor gene-modified stem cells for motor function after spinal cord injury in rodents: a systematic review and meta‑analysis.

The efficacy of growth factor gene-modified stem cells in treating spinal cord injury (SCI) remains unclear. This study aims to evaluate the effectiveness of growth factor gene-modified stem cells in restoring motor function after SCI. Two reviewers searched four databases, including PubMed, Embase, Web of Science, and Scopus, to identify relevant records. Studies on rodents assessing the efficacy of transplanting growth factor gene-modified stem cells in restoring motor function after SCI were included. The results were reported using the standardized mean difference (SMD) with a 95% confidence interval (95% CI). Analyses showed that growth factor gene-modified stem cell transplantation improved motor function recovery in rodents with SCI compared to the untreated (SMD = 3.98, 95% CI 3.26-4.70, I2 = 86.8%, P < 0.0001) and stem cell (SMD = 2.53, 95% CI 1.93-3.13, I2 = 86.9%, P < 0.0001) groups. Using growth factor gene-modified neural stem/histone cells enhanced treatment efficacy. In addition, the effectiveness increased when viral vectors were employed for gene modification and high transplantation doses were administered during the subacute phase. Stem cells derived from the human umbilical cord exhibited an advantage in motor function recovery. However, the transplantation of growth factor gene-modified stem cells did not significantly improve motor function in male rodents (P = 0.136). Transplantation of growth factor gene-modified stem cells improved motor function in rodents after SCI, but claims of enhanced efficacy should be approached with caution. The safety of gene modification remains a significant concern, requiring additional efforts to enhance its clinical translatability.

Effect of CTLA-4 Inhibition on Inflammation and Apoptosis After Spinal Cord Injury.

Spinal cord injury (SCI) encompasses various pathological processes, notably neuroinflammation and apoptosis, both of which play significant roles. CTLA-4, a well-known immune molecule that suppresses T cell-mediated immune responses, is a key area of research and a focal point for targeted therapy development in treating tumors and autoimmune disorders. Despite its prominence, the impact of CTLA-4 inhibition on inflammation and apoptosis subsequent to SCI remains unexplored. This study aimed to investigate the influence of CTLA-4 on SCI. A weight-drop technique was used to establish a rat model of SCI. To examine the safeguarding effect of CTLA-4 on the restoration of motor function in rats with SCI, the Basso-Beattie-Bresnahan (BBB) scale and inclined plane test were employed to assess locomotion. Neuronal degeneration and apoptosis were assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and Fluoro-Jade B labeling, respectively, and the activity of microglial cells was examined by immunofluorescence. To evaluate the impact of CTLA4 on SCI, the levels of inflammatory markers were measured. After treatment with the CTLA-4 inhibitor ipilimumab, the rats showed worse neurological impairment and more severe neuroinflammation after SCI. Furthermore, the combination therapy with ipilimumab and durvalumab after SCI had more pronounced effects than treatment with either inhibitor alone. These findings indicate that CTLA-4 contributes to neuroinflammation and apoptosis after SCI, presenting a promising new therapeutic target for this traumatic condition.

Combining PLGA microspheres loaded with Liver X receptor agonist GW3965 with a chitosan nerve conduit can promote the healing and regeneration of the wounded sciatic nerve.

Globally, peripheral nerve injury (PNI) is a common clinical issue. Successfully repairing severe PNIs has posed a major challenge for clinicians. GW3965 is a highly selective LXR agonist, and previous studies have demonstrated its positive protective effects in both central and peripheral nerve diseases. In this work, we examined the potential reparative effects of GW3965-loaded polylactic acid co-glycolic acid microspheres in conjunction with a chitosan nerve conduit for peripheral nerve damage. The experiment revealed that GW3965 promoted Schwann cell proliferation and neurotrophic factor release in vitro. In vivo experiments conducted on rats showed that GW3965 facilitated the restoration of motor function, promoted axon and myelin regeneration in the sciatic nerve, and enhanced the microenvironment of nerve regeneration. These results offer a novel therapeutic approach for the healing of nerve damage. Overall, this work provides valuable insights and presents a promising therapeutic strategy for addressing PNI.

Evaluation of human mononuclear umbilical cord blood cells systemic administration efficiency in the acute period of experimental severe spinal cord injury

Aim. To evaluate the efficiency of systemic (intravenous) application of cryopreserved human umbilical cord blood mononuclear cells (HUCBCs) in animal models of acute contusion spinal cord injury for the restoration of hind limb motor function and formation of posttraumatic cysts using clinically significant examination methods.Materials and methods. Adult female Sprague–Dowley rats were used for the study. Severe acute contusion spinal cord injury model was performed using standard “weight‑drop” method. All samples of cryopreserved HUCBCs concentrate were prestored prior to infusion for 3 to 4 years at –196 °C. Hind limbs motor function was evaluated using open‑field technique and standard BBB testing system. Magnetic resonance scanning was performed using high‑field magnetic resonance CleanScan 7.0 T tomography (Bruker BioSpin, Germany).Results. Intravenous infusions of HUCBCs were performed on Day 1 following acute severe spinal cord injury. Motor function assessment demonstrated significant (p &lt;0.05) improvement of hind limbs motor function (up to 40–50 %) comparing to self‑healing outcomes. Moreover, by the Days 4 and 5 after severe spinal cord injury, the volume of posttraumatic cystic cavity decreases significantly (up to 40 %) (p &lt;0.05).Conclusion. The obtained results demonstrated that cryopreserved HUCBCs can be used as an effective source for cell therapy of acute contusion spinal cord injury.

Brachial Plexus Root Avulsion Injury-Induced Endothelin-Converting Enzyme-Like 1 Overexpression Is Associated with Injured Motor Neurons Survival.

Brachial plexus root avulsion (BPRA) injury arises from challenging delivery during childbirth, sports-related incidents, or car accidents, leading to extensive loss of motor neurons (MNs) and subsequent paralysis, including both motor and sensory impairment. Surgical nerve re-implantation cannot effectively restore motor function, and the survival of injured MNs is vital for axon regeneration and re-innervating the target muscles. Therefore, identifying novel molecular targets to improve injured MNs survival is of great significance in the treatment of BPRA injuries. Endothelin-converting enzyme-like 1 (ECEL1), a membrane-bound metallopeptidase, was initially identified as a molecule associated with nerve injuries. Damaged neurons exhibit a significant increase in the expression of ECEL1 following various types of nerve injuries, such as optic nerve injury and sciatic nerve injury. This study aimed to investigate the relationship between ECEL1 overexpression and the survival of injured MNs following BPRA injury. Our results observed a significant elevation in ECEL1 expression in injured MNs and positively correlated with MNs survival following BPRA injury. The transcription of ECEL1 is regulated by the transcription factors c-Jun and ATF3 in the context of BPRA injury, which is consistent with previous other nerve injuries study. In addition, the expression of TrkA gradually decreases in ECEL1-positive MNs and ECEL1 possibly preserves the activity of downstream AKT-GSK3β pathway of TrkA in injured MNs. In conclusion, our results introduce a promising therapeutic molecular target to assist re-implantation surgery for the treatment of BPRA injury.

Integrating Simultaneous Motor Imagery and Spatial Attention for EEG-BCI Control.

EEG-based brain-computer interfaces (BCI) are non-invasive approaches for replacing or restoring motor functions in impaired patients, and direct brain-to-device communication in the general population. Motor imagery (MI) is one of the most used BCI paradigms, but its performance varies across individuals and certain users require substantial training to develop control. In this study, we propose to integrate a MI paradigm simultaneously with a recently proposed Overt Spatial Attention (OSA) paradigm, to accomplish BCI control. We evaluated a cohort of 25 human subjects' ability to control a virtual cursor in one- and two-dimensions over 5 BCI sessions. The subjects used 5 different BCI paradigms: MI alone, OSA alone, MI, and OSA simultaneously towards the same target (MI+OSA), and MI for one axis while OSA controls the other (MI/OSA and OSA/MI). Our results show that MI+OSA reached the highest average online performance in 2D tasks at 49% Percent Valid Correct (PVC), and statistically outperforms both MI alone (42%) and OSA alone (45%). MI+OSA had a similar performance to each subject's best individual method between MI alone and OSA alone (50%) and 9 subjects reached their highest average BCI performance using MI+OSA. Integrating MI and OSA leads to improved performance over both individual methods at the group level and is the best BCI paradigm option for some subjects. This work proposes a new BCI control paradigm that integrates two existing paradigms and demonstrates its value by showing that it can improve users' BCI performance.

Диагностика нутритивных нарушений у детей после перенесенной черепно-мозговой травмы (обзор современных рекомендаций)

Traumatic brain injury (TBI) is one of the main causes of disability and mortality in the population, and in young people it ranks first. Children after TBI, in addition to neurological problems, have a number of somatic ones, such as malnutrition, dysphagia, and motor disorders of the gastrointestinal tract. Hypercatabolism causes the formation of malnutrition and loss of a significant part of muscle mass in these patients. Gastrointestinal problems limit adequate nutrition. In combination with neurological disorders – motor disorders, long-term immobilization, epilepsy – this can lead to the development of sarcopenia. The presence of sarcopenia, in turn, reduces the rehabilitation potential and directly affects the restoration and acquisition of motor functions. Therefore, it is important to assess and correct nutritional status in children with TBI not only in the acute period, but also during the early restorative treatment. The purpose — to analyze the available literature on the features of assessing nutritional status in children after traumatic brain injury. Results. Children after TBI are prone to immobilization, which leads to loss of muscle mass and bone mineral density, as well as an increase in fat mass. According to the guidelines of the European Society of Pediatric Gastroenterologists, Hepatologists and Nutritionists (ESPGHAN), it is recommended to assess the nutritional status of children with neurological diseases using anthropometry, body composition, and some laboratory parameters. To date, a universal marker of nutritional status disorders in children with neurological diseases in general and with TBI in particular has not been identified. The clinical recommendations «Traumatic brain injury in children» (2022) indicate that such routine laboratory markers of nutrition assessment as total protein, serum albumin, prealbumin, retinol-binding protein, as well as anthropometry have not proven their effectiveness in assessing the state of muscle mass. The «gold standard» in determining the body composition is the bioimpedansometry method, which allows assessing the content of active cell mass, muscle mass, fat and fat-free mass, the total water content. To achieve optimal anthropometric parameters, body composition and rehabilitation prognosis, it is recommended to use indirect calorimetry instead of equations to calculate the resting energy expenditure. Conclusion. The current Federal Clinical Guidelines for the Treatment of Children with TBI (2022) do not have an algorithm and a clear approach to assessing nutritional status and prescribing nutritional support for children of this vulnerable group. To assess the nutritional status, regardless of the level of the hospital, it is recommended to use anthropometry with dynamic control. To assess the body composition it is recommended to use bioimpedansometry, if it is unavailable — mid-upper arm circumference using MUAC tapes, as well as caliperometry. It is also recommended to assess the level of trace elements, with dynamic control at 6 months or annually.

Modern advances in spinal cord regeneration: hydrogel combined with neural stem cells.

Severe spinal cord injuries (SCI) lead to loss of functional activity of the body below the injury site, affect a person's ability to self-care and have a direct impact on performance. Due to the structural features and functional role of the spinal cord in the body, the consequences of SCI cannot be completely overcome at the expense of endogenous regenerative potential and, developing over time, lead to severe complications years after injury. Thus, the primary task of this type of injury treatment is to create artificial conditions for the regenerative growth of damaged nerve fibers through the area of the SCI. Solving this problem is possible using tissue neuroengineering involving the technology of replacing the natural tissue environment with synthetic matrices (for example, hydrogels) in combination with stem cells, in particular, neural/progenitor stem cells (NSPCs). This approach can provide maximum stimulation and support for the regenerative growth of axons of damaged neurons and their myelination. In this review, we consider the currently available options for improving the condition after SCI (use of NSC transplantation or/and replacement of the damaged area of the SCI with a matrix, specifically a hydrogel). We emphasise the expediency and effectiveness of the hydrogel matrix + NSCs complex system used for the reconstruction of spinal cord tissue after injury. Since such a complex approach (a combination of tissue engineering and cell therapy), in our opinion, allows not only to creation of conditions for supporting endogenous regeneration or mechanical reconstruction of the spinal cord, but also to strengthen endogenous regeneration, prevent the spread of the inflammatory process, and promote the restoration of lost reflex, motor and sensory functions of the injured area of spinal cord.

A cell therapy approach based on iPSC-derived midbrain organoids for the restoration of motor function in a Parkinson’s disease mouse model

Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra and loss of DA transmission in the striatum, thus making cell transplantation an effective treatment strategy. Here, we develop a cellular therapy based on induced pluripotent stem cell (iPSC)-derived midbrain organoids. By transplanting midbrain organoid cells into the striatum region of a 6-OHDA-lesioned PD mouse model, we found that the transplanted cells survived and highly efficiently differentiated into DA neurons. Further, using a dopamine sensor, we observed that the differentiated human DA neurons could efficiently release dopamine and were integrated into the neural network of the PD mice. Moreover, starting from four weeks after transplantation, the motor function of the transplanted mice could be significantly improved. Therefore, cell therapy based on iPSC-derived midbrain organoids can be a potential strategy for the clinical treatment of PD.

Постоперационный контроль нейрохирургических операций у собак

Surgical operations on the spine can be accompanied by a number of complications associated with surgical access, iatrogenic neurological complications, complications associated with wound infection, and imperfect instrumentation. In this regard, not all operations lead to the expected restoration of motor function even in the initial stages of neurological disorders, and identifying the justification for routine postoperative monitoring using visual diagnostic methods (CT/MRI) in patients after spinal surgery is the main goal of this study. A sample of patients was carried out who underwent operations: ventral spondylectomy for disc extrusion, stabilization of the cervical spine for wobbler syndrome, decompression in the thoracolumbar and lumbosacral regions with and without stabilization. Thus, of the patients who underwent a control study, reoperation was required for ventral spondylectomy in 10,3 % of cases, stabilization of the cervical spine – 13,04 %, stabilization of C1-C2 – 4,1 %, hemilyaminectomy/ minihemilaminectomy in the thoracolumbar spine department – 3,5 %, hemilyaminectomy/ minihemilaminectomy in the thoracolumbar region with stabilization – 13,6 %, dorsal laminectomy L7-S1 without stabilization – 0 %, dorsal laminectomy L7-S1 with stabilization – 15,2 %.

IL-11 ameliorates oxidative stress damage in neurons after spinal cord injury by activating the JAK/STAT signaling pathway

ObjectiveExcess reactive oxygen species (ROS) generated by oxidative stress is a crucial factor affecting neuronal dysfunction after spinal cord injury (SCI). IL-11 has been reported to have antioxidative stress capacity. In the present study, we investigated the protective effect and mechanism of IL-11 against neuronal cell damage caused by oxidative imbalance. MethodsWe established a H2O2-induced oxidative stress injury model in PC12 cells and observed the effects of IL-11 on cellular activity, morphology, oxidase and antioxidant enzymes, and ROS release. Furthermore, the effect of IL-11 on apoptosis of PC12 cells was assessed by flow cytometry, a TUNEL assay and Western blotting. Transcriptome analysis and rescue experiments revealed the mechanism by which IL-11 protects neurons from oxidative stress damage. For the in vivo investigation, an adenovirus-mediated IL-11 overexpression SCI rat model was constructed to validate the beneficial effect of IL-11 against SCI. ResultsIL-11 significantly improved the viability and enhanced the antioxidant activity of H2O2-treated PC12 cells while reducing ROS release. In addition, IL-11 reduced H2O2-induced PC12 cell apoptosis. Transcriptome analysis revealed that the JAK/STAT pathway may be related to the antioxidant activity of IL-11. Treatment with a JAK/STAT inhibitor (Stattic) exacerbated the oxidative damage induced by H2O2 and attenuated the protective effects of IL-11. The results of in vivo studies showed that IL-11 prevented neuronal apoptosis due to oxidative imbalance and promoted the restoration of motor function in SCI rats by activating the JAK/STAT signaling pathway. ConclusionIL-11 inhibited oxidative stress-induced neuronal apoptosis at least in part by activating the JAK/STAT signaling pathway and further promoted the recovery of motor function. These findings suggest that IL-11 may be an effective target for the treatment for SCI.

Complanatuside A improves functional recovery after spinal cord injury through inhibiting JNK signaling-mediated microglial activation

Background and aimsComplanatuside A (ComA) is a flavonoid-rich compound in Astragalus membranaceus that has anti-inflammatory and neuroprotective effects. In this study, we focused on the effect of ComA on spinal cord injury (SCI) in mice and explored its possible mechanisms. MethodsThe SCI model was constructed using C57BL/6J mice, and the effect of ComA on motor function recovery in SCI mice was evaluated through the BMS (Basso Mouse Scale) and footprint test. The histological effects of ComA on SCI mice were evaluated by hematoxylin-eosin (H&E) staining, Luxol-fast blue (LFB) staining, and Nissl staining. In both in vivo and in vitro experiments, we detected the activation of microglia and the release of inflammatory factors through molecular experiments. Immunofluorescence and Western blotting confirmed that ComA can prevent neuronal apoptosis caused by activated microglia through the c-Jun N-terminal kinase (JNK) pathway. ResultsOur research results confirm that ComA can improve motor function in mice after SCI. Our in vitro results indicate that ComA can inhibit the activation of BV2 cells and the release of proinflammatory mediators. In addition, ComA can prevent neuronal cell apoptosis caused by activated BV2 cells. Finally, we found that ComA works through the JNK signaling pathway. ConclusionsComA can accelerate the restoration of motor function in mice after SCI, possibly by reducing neuronal apoptosis via inhibition of JNK-related signaling pathways, a reduction in microglial activation, and inhibition of inflammatory factor release. Our data indicate that ComA is a promising drug candidate for improving functional recovery in patients with SCI.

Neuromuscular implants: Interfacing with skeletal muscle for improved clinical translation of prosthetic limbs.

After an amputation, advanced prosthetic limbs can be used to interface with the nervous system and restore motor function. Despite numerous breakthroughs in the field, many of the recent research advancements have not been widely integrated into clinical practice. This review highlights recent innovations in neuromuscular implants-specifically those that interface with skeletal muscle-which could improve the clinical translation of prosthetic technologies. Skeletal muscle provides a physiologic gateway to harness and amplify signals from the nervous system. Recent surgical advancements in muscle reinnervation surgeries leverage the "bio-amplification" capabilities of muscle, enabling more intuitive control over a greater number of degrees of freedom in prosthetic limbs than previously achieved. We anticipate that state-of-the-art implantable neuromuscular interfaces that integrate well with skeletal muscle and novel surgical interventions will provide a long-term solution for controlling advanced prostheses. Flexible electrodes are expected to play a crucial role in reducing foreign body responses and improving the longevity of the interface. Additionally, innovations in device miniaturization and ongoing exploration of shape memory polymers could simplify surgical procedures for implanting such interfaces. Once implanted, wireless strategies for powering and transferring data from the interface can eliminate bulky external wires, reduce infection risk, and enhance day-to-day usability. By outlining the current limitations of neuromuscular interfaces along with potential future directions, this review aims to guide continued research efforts and future collaborations between engineers and specialists in the field of neuromuscular and musculoskeletal medicine.

Research on the progress of neurorehabilitation

With the intensification of global aging problems, the incidence of central nervous system diseases such as stroke is getting higher and higher. At the same time, the number of disabled people has also increased. Amputation and neurological diseases are important causes of disability, and neurorehabilitation is an important method for restoring the nervous function and autonomous movement ability of the disabled. At present, neurorehabilitation methods commonly used in clinical treatment mainly include: wearing prosthetic limbs, functional electrical stimulation (FES) therapy, rehabilitation robots, and so on. The prosthetic limb refers to an artificial device used to replace the function of a lost limb. Many advanced technologies are being used to improve the motion control of prosthetics to achieve natural movement. FES is a technique that can improve physiological function or treat diseases by stimulating nerves or tissues through current, and has become one of the important means to promote nerve regeneration and restore motor function. Rehabilitation robots are the equipment that uses mechanical devices and advanced control technology to assist rehabilitation treatment and functional recovery. This article mainly discusses the current research progresses of prosthetic limbs, EFS and rehabilitation robots, so as to promote the development of neurorehabilitation.

The identification of new roles for nicotinamide mononucleotide after spinal cord injury in mice: an RNA-seq and global gene expression study.

Nicotinamide mononucleotide (NMN), an important transforming precursor of nicotinamide adenine dinucleotide (NAD+). Numerous studies have confirmed the neuroprotective effects of NMN in nervous system diseases. However, its role in spinal cord injury (SCI) and the molecular mechanisms involved have yet to be fully elucidated. We established a moderate-to-severe model of SCI by contusion (70 kdyn) using a spinal cord impactor. The drug was administered immediately after surgery, and mice were intraperitoneally injected with either NMN (500 mg NMN/kg body weight per day) or an equivalent volume of saline for seven days. The central area of the spinal cord was harvested seven days after injury for the systematic analysis of global gene expression by RNA Sequencing (RNA-seq) and finally validated using qRT-PCR. NMN supplementation restored NAD+ levels after SCI, promoted motor function recovery, and alleviated pain. This could potentially be associated with alterations in NAD+ dependent enzyme levels. RNA sequencing (RNA-seq) revealed that NMN can inhibit inflammation and potentially regulate signaling pathways, including interleukin-17 (IL-17), tumor necrosis factor (TNF), toll-like receptor, nod-like receptor, and chemokine signaling pathways. In addition, the construction of a protein-protein interaction (PPI) network and the screening of core genes showed that interleukin 1β (IL-1β), interferon regulatory factor 7 (IRF 7), C-X-C motif chemokine ligand 10 (Cxcl10), and other inflammationrelated factors, changed significantly after NMN treatment. qRT-PCR confirmed the inhibitory effect of NMN on inflammatory factors (IL-1β, TNF-α, IL-17A, IRF7) and chemokines (chemokine ligand 3, Cxcl10) in mice following SCI. The reduction of NAD+ levels after SCI can be compensated by NMN supplementation, which can significantly restore motor function and relieve pain in a mouse model. RNA-seq and qRT-PCR systematically revealed that NMN affected inflammation-related signaling pathways, including the IL-17, TNF, Toll-like receptor, NOD-like receptor and chemokine signaling pathways, by down-regulating the expression of inflammatory factors and chemokines.

PEG-chitosan (Neuro-PEG) induced restoration of motor function after complete transection of the dorsal spinal cord in swine. A pilot study

Background: Spinal cord injury (SCI) remains an unmet medical need. Recently, fusogens, such as polyethylene glycol (PEG), have been proven effective in restoring sensorimotor function after complete transection of the spinal cord at different levels and in different species. Here, we report on the use of a PEG-chitosan combo in a different animal model (swine). Methods: Five Hungarian Mangalica pigs were subjected to complete transection of the thoracic cord (T7-9). Three animals were treated with locally injected PEG-chitosan (Neuro-PEG) gel; two acted as controls. PEG-600 was also injected intra- and post-operatively intravenously. Animals were submitted to rehabilitation, including electrical myostimulation. Results were assessed after 60 days using the Individual Limb Motor Score, the Porcine Thoracic Spinal Cord Injured Behavioral Scale, and the modified motor Basso, Beattie, and Bresnahan scale; sensory and sphincter functions were also assessed. Animals underwent in vivo spinal cord tracing with DiI. Immunofluorescence histology included NF-200, DAPI, and a fluorochrome-conjugated secondary antibody. Results: Starting on postoperative day (POD) 2, neuro-PEG-treated animals evinced the first signs of recovery, and on POD 60, they could all support their weight and were mobile. Controls never recovered any useful function. Fluorescence microscopy in the experimental group revealed axons passing through the site of injury, while degenerative post-traumatic changes were noted in controls. Conclusion: Neuro-PEG affords sensorimotor recovery after complete spinal cord transection. This opens the door to human experimentation, including trials of spinal cord transplantation.

Melt Electrowriting: A Promising 3D Printing Technology for Cartilage and Osteochondral Repair

AbstractArticular cartilage injuries and osteochondral defects are a significant clinical challenge, as conventional treatments often have limited success. Articular cartilage has limited self‐regeneration ability due to the absence of blood vessels, nerves, and lymphatic vessels, making it challenging to repair tissue defects and restore motor function in injured or aging populations. Additionally, the anatomical complexity and slow regeneration capacity of hyaline cartilage at the osteochondral interface pose significant problems in repairing osteochondral defects. Melt electrowriting, a novel technology particularly suitable for polycaprolactone (PCL) is expected to overcome the common limitations of 3D‐printed scaffolds, such as poor tissue‐porosity matching, low resolution, and inflexible shapes. In recent years, melt electrowriting (MEW) has become a promising strategy for repairing cartilage and osteochondral defects. However, there is still a lack of systematic understanding regarding the comparative characteristics and application value of MEW compared with commonly used 3D printing technologies such as extrusion printing, inkjet printing, and fusion deposition modeling. This review paper compares the characteristics and advantages of MEW and common 3D printing technologies, providing a comprehensive summary of the significant progress and applications of MEW for cartilage/osteochondral repair. Finally, the challenges and key directions for future research in MEW technology will also be discussed.

Doping-induced assembly interface for noninvasive in vivo local and systemic immunomodulation.

Peripheral neural interfaces, potent in modulating local and systemic immune responses for disease treatment, face significant challenges due to the peripheral nerves' broad distribution in tissues like the fascia, periosteum, and skin. The incongruity between static electronic components and the dynamic, complex organization of the peripheral nervous system often leads to interface failure, stalling circuit research and clinical applications. To overcome these, we developed a self-assembling, tissue-adaptive electrode composed of a single-component cocktail nanosheet colloid, including dopants, conducting polymers, stabilizers, and an MXene catalyst. Delivered via a jet injector to designated nerve terminals, this assembly utilizes reactive oxygen species to catalytically dope poly (3,4-ethylenedioxythiophene), enhancing π-π interactions between nanosheets, and yielding a conductive, biodegradable interface. This interface effectively regulates local immune activity and promotes sensory and motor nerve functional restoration in nerve-injured mice, while engaging the vagal-adrenal axis in freely moving mice, eliciting catecholamine neurotransmitter release, and suppressing systemic cytokine storms. This innovative strategy specifically targets nerve substructures, bolstering local and systemic immune modulation, and paving the way for the development of self-adaptive dynamic neural interfaces.

Biomimicking 3D soft scaffold combined with electrical stimulation to manipulate neural stem cell differentiation for guidance spinal cord injury repair

Spinal cord injury repair has remained a challenging issue in the medical field, and in recent years neural stem cell-based therapies have shown great potential. However, the survival and controlled differentiation of neural stem cells (NSCs) remain a problem, since the majority of materials can’t provide a suitable microenvironment for NSCs. In this work, we design and develop a conductive hydrogel mimicking spinal cord tissue as a biomimetic 3D biomaterial soft scaffold to improve the survival microenvironment and regulate the differentiation direction of NSCs. Significantly, the designed hydrogel matches the spinal cord tissue in aspects of mechanical properties, electrical conductivity, and pore structure. Moreover, the hydrogel possesses injectability, self-healing and haemostatic properties. Combining hydrogel with electrical stimulation (ES) induces loaded NSCs to be more inclined toward neuronal differentiation, axonal growth, and myelin regeneration, while reducing astrocyte development. This treatment strategy will ultimately achieve spinal cord injury repair and motor function restoration while avoiding glial scar deposition. This mimicking spinal cord 3D soft scaffolds combined with ES provide a promising therapeutic strategy for spinal cord injury repair.

Sensorimotor rhythm and muscle activity in patients with stroke using mobile serious games to assist upper extremity rehabilitation.

Exercise rehabilitation is crucial for neurological recovery in hemiplegia-induced upper limb dysfunction. Technology-assisted cortical activation in sensorimotor areas has shown potential for restoring motor function. This study assessed the feasibility of mobile serious games for stroke patients' motor rehabilitation. A dedicated mobile application targeted shoulder, elbow, and wrist training. Twelve stroke survivors attempted a motor task under two conditions: serious mobile game-assisted and conventional rehabilitation. Electroencephalography and electromyography measured the therapy effects. Patients undergoing game-assisted rehabilitation showed stronger event-related desynchronization (ERD) in the contralateral hemisphere's motor perception areas compared to conventional rehabilitation (p < 0.05). RMS was notably higher in game-assisted rehabilitation, particularly in shoulder training (p < 0.05). Serious mobile game rehabilitation activated the motor cortex without directly improving muscle activity. This suggests its potential in neurological recovery for stroke patients.