Reduced Graphene Oxide Fibers Combined with Electrical Stimulation Promote Peripheral Nerve Regeneration.

Background: The treatment of long-gap peripheral nerve injury (PNI) is still a substantial clinical problem. Graphene-based scaffolds possess extracellular matrix (ECM) characteristic and can conduct electrical signals, therefore have been investigated for repairing PNI. Combined with electrical stimulation (ES), a well performance should be expected. We aimed to determine the effects of reduced graphene oxide fibers (rGOFs) combined with ES on PNI repair in vivo. Methods: rGOFs were prepared by one-step dimensionally confined hydrothermal strategy (DCH). Surface characteristics, chemical compositions, electrical and mechanical properties of the samples were characterized. The biocompatibility of the rGOFs were systematically explored both in vitro and in vivo. Total of 54 Sprague-Dawley (SD) rats were randomized into 6 experimental groups: a silicone conduit (S), S+ES, S+rGOFs-filled conduit (SGC), SGC+ES, nerve autograft, and sham groups for a 10-mm sciatic defect. Functional and histological recovery of the regenerated sciatic nerve at 12 weeks after surgery in each group of SD rats were evaluated. Results: rGOFs exhibited aligned micro- and nano-channels with excellent mechanical and electrical properties. They are biocompatible in vitro and in vivo. All 6 groups exhibited PNI repair outcomes in view of neurological and morphological recovery. The SGC+ES group achieved similar therapeutic effects as nerve autograft group (P > 0.05), significantly outperformed other treatment groups. Immunohistochemical analysis showed that the expression of proteins related to axonal regeneration and angiogenesis were relatively higher in the SGC+ES. Conclusion: The rGOFs had good biocompatibility combined with excellent electrical and mechanical properties. Combined with ES, the rGOFs provided superior motor nerve recovery for a 10-mm nerve gap in a murine acute transection injury model, indicating its excellent repairing ability. That the similar therapeutic effects as autologous nerve transplantation make us believe this method is a promising way to treat peripheral nerve defects, which is expected to guide clinical practice in the future.

Effects of adipose-derived cell supplementation on tendon-bone healing in a rat model of chronic rotator cuff tear with suprascapular nerve injury.

OBJECTIVE: To investigate the effect of adipose-derived cells (ADCs) on tendon-bone healing in a rat model of chronic rotator cuff tear (RCT) with suprascapular nerve (SN) injury. METHODS: Adult rats underwent right shoulder surgery whereby the supraspinatus was detached, and SN injury was induced. ADCs were cultured from the animals' abdominal fat. At 6 weeks post-surgery, the animals underwent surgical tendon repair; the ADC (+ve) group (n = 18) received an ADC injection, and the ADC (-ve) group (n = 18) received a saline injection. Shoulders were harvested at 10, 14, and 18 weeks and underwent histological, fluorescent, and biomechanical analyses. RESULTS: In the ADC (+ve) group, a firm enthesis, including dense mature fibrocartilage and well-aligned cells, were observed in the bone-tendon junction and fatty infiltration was less than in the ADC (-ve) group. Mean maximum stress and linear stiffness was greater in the ADC (+ve) compared with the ADC (-ve) group at 18 weeks. CONCLUSION: ADC supplementation showed a positive effect on tendon-bone healing in a rat model of chronic RCT with accompanying SN injury. Therefore, ADC injection may possibly accelerate recovery in massive RCT injuries.

Differentiated mesenchymal stem cells-derived exosomes immobilized in decellularized sciatic nerve hydrogels for peripheral nerve repair.

Peripheral nerve injury (PNI) and the limitations of current treatments often result in incomplete sensory and motor function recovery, which significantly impact the patient's quality of life. While exosomes (Exo) derived from stem cells and Schwann cells have shown promise on promoting PNI repair following systemic administration or intraneural injection, achieving effective local and sustained Exo delivery holds promise to treat local PNI and remains challenging. In this study, we developed Exo-loaded decellularized porcine nerve hydrogels (DNH) for PNI repair. We successfully isolated Exo from differentiated human adipose-derived mesenchymal stem cells (hADMSC) with a Schwann cell-like phenotype (denoted as dExo). These dExo were further combined with polyethylenimine (PEI), and DNH to create polyplex hydrogels (dExo-loaded pDNH). At a PEI content of 0.1%, pDNH showed cytocompatibility for hADMSCs and supported neurite outgrowth of dorsal root ganglions. The sustained release of dExos from dExo-loaded pDNH persisted for at least 21 days both in vitro and in vivo. When applied around injured nerves in a mouse sciatic nerve crush injury model, the dExo-loaded pDNH group significantly improved sensory and motor function recovery and enhanced remyelination compared to dExo and pDNH only groups, highlighting the synergistic regenerative effects. Interestingly, we observed a negative correlation between the number of colony-stimulating factor-1 receptor (CSF-1R) positive cells and the extent of PNI regeneration at the 21-day post-surgery stage. Subsequent in vitro experiments demonstrated the potential involvement of the CSF-1/CSF-1R axis in Schwann cells and macrophage interaction, with dExo effectively downregulating CSF-1/CSF-1R signaling.

Immune-cell-mediated tissue engineering strategies for peripheral nerve injury and regeneration.

During the process of peripheral nerve repair, there are many complex pathological and physiological changes, including multi-cellular responses and various signaling molecules, and all these events establish a dynamic microenvironment for axon repair, regeneration, and target tissue/organ reinnervation. The immune system plays an indispensable role in the process of nerve repair and function recovery. An effective immune response not only involves innate-immune and adaptive-immune cells but also consists of chemokines and cytokines released by these immune cells. The elucidation of the orchestrated interplay of immune cells with nerve regeneration and functional restoration is meaningful for the exploration of therapeutic strategies. This review mainly enumerates the general immune cell response to peripheral nerve injury and focuses on their contributions to functional recovery. The tissue engineering-mediated strategies to regulate macrophages and T cells through physical and biochemical factors combined with scaffolds are discussed. The dynamic immune responses during peripheral nerve repair and immune-cell-mediated tissue engineering methods are presented, which provide a new insight and inspiration for immunomodulatory therapies in peripheral nerve regeneration.

TsMS combined with EA promotes functional recovery and axonal regeneration via mediating the miR-539-5p/Sema3A/PlexinA1 signalling axis in sciatic nerve-injured rats.

Enhancing axonal regeneration is one of the most important processes in treating nerve injuries. Both magnetic and electrical stimulation have the effect of promoting nerve axon regeneration. But few study has investigated the effects of trans-spinal magnetic stimulation (TsMS) combined with electroacupuncture (EA) on nerve regeneration in rats with sciatic nerve injury. In this study, we compared the improvement of neurological function in rats with sciatic nerve crush injuries after 4 weeks of different interventions (EA, TsMS, or TsMS combined with EA). We further explored the morphological and molecular biological alterations following sciatic nerve injury by HE, Masson, RT-PCR, western blotting, immunofluorescence staining and small RNA transcriptome sequencing. The results showed that TsMS combined with EA treatment significantly promoted axonal regeneration, increased the survival rate of neurons, and suppressed denervation atrophy of the gastrocnemius muscle. Subsequent experiments suggested that the combination treatment may play an active role by mediating the miR-539-5p/Sema3A/PlexinA1 signaling axis.

Sports-related peripheral nerve injuries of the upper limb.

Peripheral nerve injuries in athletes affect the upper limb more commonly than the lower limb. Common mechanisms include compression, traction, laceration, and ischemia. Specific sports can have unique mechanisms of injury and are more likely to be associated with certain neuropathies. Familiarity with these sport-specific variables and recognition of the common presentations of upper limb neuropathic syndromes are important in assessing an athlete with a suspected peripheral nerve injury. Evaluation may require imaging modalities and/or electrodiagnostic testing to confirm a nerve injury. In some cases, diagnostic injections may be needed to differentiate neuropathic versus musculoskeletal etiology. Early and accurate diagnosis is essential for treatment/management and increases the likelihood of a safe return-to-sport and avoidance of long-term functional consequences. Most nerve injuries can be treated conservatively, however, severe or persistent cases may require surgical intervention. This monograph reviews key diagnostic, management, and preventative strategies for sports-related peripheral nerve injuries involving the upper limb.

Exploration of outcome measures for assessing orthotic intervention in upper extremity peripheral nerve injuries: 2 case reports.

In upper extremity peripheral nerve injuries, orthotic intervention has been used as a valuable device to restore function. However, there is lacking evidence to support it. The purpose of this study was to explore the application of body function's outcome measures for orthotic intervention evaluation in patients with peripheral nerve injury. Two participants sustaining a peripheral nerve injury who underwent orthotic intervention were assessed: subject 1 was a 25-year-old man with ulnar and median nerve injury presenting with a composite claw; subject 2, a 28-year-old man with radial nerve injury presenting with a dropped wrist. Strength, range of motion, and electromyography were measured in 2 conditions: wearing the orthosis and without it. The Jamar, Pinch Gauge, a 3D motion capture system (Optitrack-NaturalPoint), and surface electromyography (Trigno Wireless System, Delsys) were the chosen instruments. Both subjects presented differences in grip and pinch strength. In both tasks, subject 1 reached higher wrist extension while wearing the orthosis. Subject 2 reached higher wrist extension and radial deviation while wearing the orthosis. There were marked differences in both tasks for subject 2, especially the maintenance of wrist extension when wearing the orthosis. Electromyographic assessment showed higher root-mean-square values for all muscles, in both tasks for subject 1. For subject 2, a higher root-mean-square value was found for flexor carpi ulnaris during the execution of task 1 wearing the orthosis. Outcome measures of body function can quantify the impact of orthotic intervention in patients sustaining peripheral nerve injury, and therefore, they are feasible for evaluating it.

Rab32 facilitates Schwann cell pyroptosis in rats following peripheral nerve injury by elevating ROS levels.

BACKGROUND: Peripheral nerve injury (PNI) is commonly observed in clinical practice, yet the underlying mechanisms remain unclear. This study investigated the correlation between the expression of a Ras-related protein Rab32 and pyroptosis in rats following PNI, and potential mechanisms have been explored by which Rab32 may influence Schwann cells pyroptosis and ultimately peripheral nerve regeneration (PNR) through the regulation of Reactive oxygen species (ROS) levels. METHODS: The authors investigated the induction of Schwann cell pyroptosis and the elevated expression of Rab32 in a rat model of PNI. In vitro experiments revealed an upregulation of Rab32 during Schwann cell pyroptosis. Furthermore, the effect of Rab32 on the level of ROS in mitochondria in pyroptosis model has also been studied. Finally, the effects of knocking down the Rab32 gene on PNR were assessed, morphology, sensory and motor functions of sciatic nerves, electrophysiology and immunohistochemical analysis were conducted to assess the therapeutic efficacy. RESULTS: Silencing Rab32 attenuated PNI-induced Schwann cell pyroptosis and promoted peripheral nerve regeneration. Furthermore, our findings demonstrated that Rab32 induces significant oxidative stress by damaging the mitochondria of Schwann cells in the pyroptosis model in vitro. CONCLUSION: Rab32 exacerbated Schwann cell pyroptosis in PNI model, leading to delayed peripheral nerve regeneration. Rab32 can be a potential target for future therapeutic strategy in the treatment of peripheral nerve injuries.

Effect of Long-term Peripheral Nerve Stimulation on Neuro-Muscular Complex Morphologic Recovery in Experiment / Efecto de la Estimulación del Nervio Periférico a Largo Plazo sobre la Recuperación Morfológica del Complejo Neuromuscular en Experimento

SUMMARY: Peripheral nerve injury is an extremely important medical and socio-economic problem. It is far from a solution, despite on rapid development of technologies. To study the effect of long-term electrical stimulation of peripheral nerves, we used a domestically produced electrical stimulation system, which is approved for clinical use. The study was performed on 28 rabbits. Control of regeneration was carried out after 3 month with morphologic techniques. The use of long-term electrostimulation technology leads to an improvement in the results of the recovery of the nerve trunk after an injury, both directly at the site of damage, when stimulation begins in the early period, and indirectly, after the nerve fibers reach the effector muscle.

La lesión de los nervios periféricos es un problema médico y socioeconómico extremadamente importante. Sin embargo, y a pesar del rápido desarrollo de las tecnologías, aún no tiene solución. Para estudiar el efecto de la estimulación eléctrica a largo plazo de los nervios periféricos, utilizamos un sistema de estimulación eléctrica de producción nacional, que está aprobado para uso clínico. El estudio se realizó en 28 conejos. El control de la regeneración se realizó a los 3 meses con técnicas morfológicas. El uso de tecnología de electro estimulación a largo plazo conduce a una mejora en los resultados de la recuperación del tronco nervioso después de una lesión, tanto directamente en el lugar del daño, cuando la estimulación comienza en el período temprano, como indirectamente, después de que las fibras nerviosas alcanzan el músculo efector.

Efficacy of collagen conduit wrapping with collagen fibers on nerve regeneration in sciatic nerve injury with partial transection: An experimental study in the rat model.

Peripheral nerve injuries (PNIs) include complete and partial transection, crushing, and chronic compression injuries. Hollow absorbable conduits are used to treat complete transection with short defects, while wrapping the injured part with an absorbent material promotes nerve recovery by inhibiting inflammatory cell infiltration and scar tissue formation in crush injuries. For treatment of partially transected nerve injuries (PTNIs), such as injection-related iatrogenic PNI, whether wrapping the entire nerve, including the injury site, or bridging the transected fascicle with an artificial nerve conduit (ANC) is beneficial remains to be verified. The purpose of this study was to investigate whether wrapping the injured nerve and placing collagen fibers as scaffolds at the nerve defect site contribute to neural recovery in PTNI. A unilateral 5-mm partial nerve defect was created at the mid-thigh level in a rat sciatic nerve injury model. Fifty-four Sprague-Dawley (SD) rats (150-250 g) were divided into three groups (n = 9 each): group 1, collagen fibers were placed in the nerve defect and the sciatic nerve was wrapped with collagen conduit; group 2, the sciatic nerve was wrapped by collagen conduit without collagen fibers; and group 3, nerve defect was reconstructed with collagen-filled conduit. Nerve regeneration was evaluated by analyses of gait, electrophysiology, wet muscle weight, and axon numbers with immunohistochemistry at 12 and 24 weeks. Dorsiflexion angles among all groups improved significantly from 12 to 24 weeks postoperatively. At 24 weeks postoperatively, compound muscle action potential amplitudes (CMAPs) of tibialis anterior were 5.26 ± 4.64, 1.31 ± 1.17, and 0.14 ± 0.24 mV (p < .05), CMAPs of gastrocnemius were 21.3 ± 5.98, 15.4 ± 5.46, and 13.11 ± 3.91 mV in groups 1, 2, and 3, respectively; and the value of group 1 was significantly higher than that of group 3 (p < .05). Axon numbers were 2194 ± 629; 1106 ± 645; and 805 ± 907 in groups 1, 2, and 3, respectively (p < .05). For PTNI reconstruction, artificial nerve wrap (ANW) was superior to ANC. Providing collagen scaffold at the nerve defect site enhanced nerve recovery during reconstruction with ANW.

Platelet-rich plasma-derived exosomes boost mesenchymal stem cells to promote peripheral nerve regeneration.

Peripheral nerve injury (PNI) remains a severe clinical problem with debilitating consequences. Mesenchymal stem cell (MSC)-based therapy is promising, but the problems of poor engraftment and insufficient neurotrophic effects need to be overcome. Herein, we isolated platelet-rich plasma-derived exosomes (PRP-Exos), which contain abundant bioactive molecules, and investigated their potential to increase the regenerative capacity of MSCs. We observed that PRP-Exos significantly increased MSC proliferation, viability, and mobility, decreased MSC apoptosis under stress, maintained MSC stemness, and attenuated MSC senescence. In vivo, PRP-Exo-treated MSCs (pExo-MSCs) exhibited an increased retention rate and heightened therapeutic efficacy, as indicated by increased axonal regeneration, remyelination, and recovery of neurological function in a PNI model. In vitro, pExo-MSCs coculture promoted Schwann cell proliferation and dorsal root ganglion axon growth. Moreover, the increased neurotrophic behaviour of pExo-MSCs was mediated by trophic factors, particularly glia-derived neurotrophic factor (GDNF), and PRP-Exos activated the PI3K/Akt signalling pathway in MSCs, leading to the observed phenotypes. These findings demonstrate that PRP-Exos may be novel agents for increasing the ability of MSCs to promote neural repair and regeneration in patients with PNI.

Magnetoactive Composite Conduits Based on Poly(3-hydroxybutyrate) and Magnetite Nanoparticles for Repair of Peripheral Nerve Injury.

Peripheral nerve injury poses a threat to the mobility and sensitivity of a nerve, thereby leading to permanent function loss due to the low regenerative capacity of mature neurons. To date, the most widely clinically applied approach to bridging nerve injuries is autologous nerve grafting, which faces challenges such as donor site morbidity, donor shortages, and the necessity of a second surgery. An effective therapeutic strategy is urgently needed worldwide to overcome the current limitations. Herein, a magnetic nerve guidance conduit (NGC) based on biocompatible biodegradable poly(3-hydroxybutyrate) (PHB) and 8 wt % of magnetite nanoparticles modified by citric acid (Fe3O4-CA) was fabricated by electrospinning. The crystalline structure of NGCs was studied by X-ray diffraction, which indicated an enlarged ß-phase of PHB in the composite conduit compared to a pure PHB conduit. Tensile tests revealed greater ductility of PHB/Fe3O4-CA: the composite conduit has Young's modulus of 221 ± 52 MPa and an elongation at break of 28.6 ± 2.9%, comparable to clinical materials. Saturation magnetization (σs) of Fe3O4-CA and PHB/Fe3O4-CA is 61.88 ± 0.29 and 7.44 ± 0.07 emu/g, respectively. The water contact angle of the PHB/Fe3O4-CA conduit is lower as compared to pure PHB, while surface free energy (σ) is significantly higher, which was attributed to higher surface roughness and an amorphous phase as well as possible PHB/Fe3O4-CA interface interactions. In vitro, the conduits supported the proliferation of rat mesenchymal stem cells (rMSCs) and SH-SY5Y cells in a low-frequency magnetic field (0.67 Hz, 68 mT). In vivo, the conduits were used to bridge damaged sciatic nerves in rats; pure PHB and composite PHB/Fe3O4-CA conduits did not cause acute inflammation and performed a barrier function, which promotes nerve regeneration. Thus, these conduits are promising as implants for the regeneration of peripheral nerves.

Mesenchymal Stem Cell-Derived Mitochondria Enhance Extracellular Matrix-Derived Grafts for the Repair of Nerve Defect.

Peripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High-purity functional mitochondria with an intact structure are extracted from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC-derived mitochondria (hUCMSC-Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC-Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC-Mito-loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair.

Electroacupuncture Promotes Nerve Regeneration and Functional Recovery Through Regulating lncRNA GAS5 Targeting miR-21 After Sciatic Nerve Injury.

Although the benefits of electroacupuncture (EA) for peripheral nerve injury (PNI) are well accepted in clinical practice, the underlying mechanism remains incompletely elucidated. In our study, we observed that EA intervention led to a reduction in the expression of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5) and an increased in miR-21 levels within the injured nerve, effectively promoting functional recovery and nerve regeneration following sciatic nerve injury (SNI). In contrast, administration of adeno-associated virus expressing GAS5 (AAV-GAS5) weakened the therapeutic effect of EA. On the other hand, both silencing GAS5 and introducing a miR-21 mimic prominently enhanced the proliferation activity and migration ability of Schwann cells (SCs), while also inhibiting SCs apoptosis. On the contrary, inhibition of SCs apoptosis was found to be mediated by miR-21. Additionally, overexpression of GAS5 counteracted the effects of the miR-21 mimic on SCs. Moreover, SCs that transfected with the miR-21 mimic promoted neurite growth in hypoxia/reoxygenation-induced neurons, which might be prevented by overexpressing GAS5. Furthermore, GAS5 was found to be widely distributed in the cytoplasm and was negatively regulated by miR-21. Consequently, the targeting of GAS5 by miR-21 represents a potential mechanism through which EA enhances reinnervation and functional restoration following SNI. Mechanistically, the GAS5/miR-21 axis can modulate the proliferation, migration, and apoptosis of SCs while potentially influencing the neurite growth of neurons.

Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation.

Skeletal muscle is striated muscle that moves autonomously and is innervated by peripheral nerves. Peripheral nerve injury is very common in clinical treatment. However, the commonly used treatment methods often focus on the regeneration of the injured nerve but overlook the pathological changes in the injured skeletal muscle. Acupuncture, as the main treatment for denervated skeletal muscle atrophy, is used extensively in clinical practice. In the present study, a mouse model of lower limb sciatic nerve detachment was constructed and treated with electroacupuncture Stomach 36 to observe the atrophy of lower limb skeletal muscle and changes in skeletal muscle fibre types before and after electroacupuncture Stomach 36 treatment. Mice with skeletal muscle denervation showed a decrease in the proportion of IIa muscle fibres and an increase in the proportion of IIb muscle fibres, after electroacupuncture Stomach 36. The changes were reversed by specific activators of p38 MAPK, which increased IIa myofibre ratio. The results suggest that electroacupuncture Stomach 36 can reverse the change of muscle fibre type from IIb to IIa after denervation of skeletal muscle by inhibiting p38 MAPK. The results provide an important theoretical basis for the treatment of clinical peripheral nerve injury diseases with electroacupuncture, in addition to novel insights that could facilitate the study of pathological changes of denervated skeletal muscle.

Electrical Stimulation Use in Upper Extremity Peripheral Nerve Injuries.

Peripheral nerve injuries can be debilitating and often have a variable course of recovery. Electrical stimulation (ES) has been used as an intervention to attempt to overcome the limits of peripheral nerve surgery and improve patient outcomes after peripheral nerve injury. Little has been written in the orthopaedic literature regarding the use of this technology. The purpose of this review was to provide a focused analysis of past and current literature surrounding the utilization of ES in the treatment of various upper extremity peripheral nerve pathologies including compression neuropathies and nerve transection. We aimed to provide clarity on the clinical benefits, appropriate timing for its employment, risks and limitations, and the need for future studies of ES.

Enhancement of nerve regeneration through schwann cell-mediated healing in a 3D printed polyacrylonitrile conduit incorporating hydrogel and graphene quantum dots: a study on rat sciatic nerve injury model.

Despite recent technological advancements, effective healing from sciatic nerve damage remains inadequate. Cell-based therapies offer a promising alternative to autograft restoration for peripheral nerve injuries, and 3D printing techniques can be used to manufacture conduits with controlled diameter and size. In this study, we investigated the potential of Wharton's jelly-derived mesenchymal stem cells (WJMSCs) differentiated into schwann cells, using a polyacrylonitrile (PAN) conduit filled with fibrin hydrogel and graphene quantum dots (GQDs) to promote nerve regeneration in a rat sciatic nerve injury model. We investigated the potential of WJMSCs, extracted from the umbilical cord, to differentiate into schwann cells and promote nerve regeneration in a rat sciatic nerve injury model. WJMSCs were 3D cultured and differentiated into schwann cells within fibrin gel for two weeks. A 3 mm defect was created in the sciatic nerve of the rat model, which was then regenerated using a conduit/fibrin, conduit covered with schwann cells in fibrin/GQDs, GQDs in fibrin, and a control group without any treatment (n= 6/group). At 10 weeks after transplantation, motor and sensory functions and histological improvement were assessed. The WJMSCs were extracted, identified, and differentiated. The differentiated cells expressed typical schwann cell markers, S100 and P75.In vivoinvestigations established the durability and efficacy of the conduit to resist the pressures over two months of implantation. Histological measurements showed conduit efficiency, schwann cell infiltration, and association within the fibrin gel and lumen. Rats treated with the composite hydrogel-filled PAN conduit with GQDs showed significantly higher sensorial recovery than the other groups. Histological results showed that this group had significantly more axon numbers and remyelination than others. Our findings suggest that the conduit/schwann approach has the potential to improve nerve regeneration in peripheral nerve injuries, with future therapeutic implications.

Hybrid Electrically Conductive Hydrogels with Local Nerve Growth Factor Release Facilitate Peripheral Nerve Regeneration.

It is challenging to treat peripheral nerve injury (PNI) clinically. As the gold standard for peripheral nerve repair, autologous nerve grafting remains a critical limitation, including tissue availability, donor-site morbidity, immune rejection, etc. Recently, conductive hydrogels (CHs) have shown potential applications in neural bioengineering due to their good conductivity, biocompatibility, and low immunogenicity. Herein, a hybrid electrically conductive hydrogel composed of acrylic acid derivatives, gelatin, and heparin with sustained nerve growth factor (NGF) release property was developed. The rat sciatic nerve injury (SNI) model (10 mm long segment defect) was used to investigate the efficacy of these hydrogel conduits in facilitating peripheral nerve repair. The results showed that the hydrogel conduits had excellent conductivity, mechanical properties, and biocompatibility. In addition, NGF immobilized in the hydrogel conduits had good sustained release characteristics. Finally, functional recovery and electrophysiological evaluations, together with histological analysis, indicated that the hydrogel conduits immobilizing NGF had superior effects on motor recovery, axon growth, and remyelination, thereby significantly accelerating the repairing of the sciatic nerve. This study demonstrated that hybrid electrically conductive hydrogels with local NGF release could be effectively used for PNI repair.

Potential therapeutic effect of olfactory ensheathing cells in neurological diseases: neurodegenerative diseases and peripheral nerve injuries.

Neurological diseases are destructive, mainly characterized by the failure of endogenous repair, the inability to recover tissue damage, resulting in the increasing loss of cognitive and physical function. Although some clinical drugs can alleviate the progression of these diseases, but they lack therapeutic effect in repairing tissue injury and rebuilding neurological function. More and more studies have shown that cell therapy has made good achievements in the application of nerve injury. Olfactory ensheathing cells (OECs) are a special type of glial cells, which have been proved to play an important role as an alternative therapy for neurological diseases, opening up a new way for the treatment of neurological problems. The functional mechanisms of OECs in the treatment of neurological diseases include neuroprotection, immune regulation, axon regeneration, improvement of nerve injury microenvironment and myelin regeneration, which also include secreted bioactive factors. Therefore, it is of great significance to better understand the mechanism of OECs promoting functional improvement, and to recognize the implementation of these treatments and the effective simulation of nerve injury disorders. In this review, we discuss the function of OECs and their application value in the treatment of neurological diseases, and position OECs as a potential candidate strategy for the treatment of nervous system diseases.

Emerging 4D fabrication of next-generation nerve guiding conduits: a critical perspective.

The latest advancements in the field of manufacturing for biomedicine, digital health, targeted therapy, and personalized medicine have fuelled the fabrication of smart medical devices. Four-dimensional (4D) fabrication strategies, which combine the manufacturing of three-dimensional (3D) parts with smart materials and/or design, have proved beneficial in creating customized and self-fitting structures that change their properties on demand with time. These frontier techniques that yield dynamic implants can indeed alleviate various drawbacks of current clinical practices, such as the use of sutures and complex microsurgeries and associated inflammation, among others. Among various clinical applications, 4D fabrication has lately made remarkable progress in the development of next-generation nerve-guiding conduits for treating peripheral nerve injuries (PNIs) by improving the end-to-end co-aptation of transected nerve endings. The current perspective highlights the relevance of 4D fabrication in developing state-of-the-art technologies for the treatment of PNIs. Various 4D fabrication/bio-fabrication techniques for PNI treatment are summarized while identifying the challenges and opportunities for the future. Such advancements hold immense promise for improving the quality of life of patients suffering from nerve damage and the potential for extending the treatment of many other disorders. Although the techniques are being described for PNIs, they will lend themselves suitably to certain cases of cranial nerve injuries as well.