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Peripheral nerve injury significantly impairs sensory and motor functions, leading to diminished quality of life. Traditional treatments like nerve suturing and grafting often have limited efficacy and require long recovery. Recent advances in electrical stimulation technology show promise in speeding nerve repair, but current devices usually require lengthy surgeries, risking secondary nerve injury from prolonged nerve exposure during electrode installation and removal. This study introduces a portable, absorbable electrical stimulation system (PAESS) that integrates a battery‐free, wirelessly powered flexible printed circuit board chip with a biodegradable organic electrode. PAESS enables multiple self‐administered nerve stimulation without the need for electrode installation or removal. Using animal models, its electrical performance, biocompatibility, and efficacy in nerve repair are evaluated. The findings indicate a considerable enhancement in the recovery of nerve function, as demonstrated by improved electrophysiological measurements, decreased muscle atrophy, and positive histological results. Transcriptomic analysis indicates that the PAESS initiates the nerve regeneration process. This research presents an innovative platform for electrical stimulation, laying the groundwork for exploring electrical parameters and their mechanisms. This may deepen understanding of nerve regeneration and foster innovation in therapies. [ABSTRACT FROM AUTHOR]

Low‐intensity pulsed ultrasound (LIPUS) and electrical stimulation (ES) are effective methods that promote neural repair. However, ES usually requires electrode implantation and a power supply, which are an inconvenience to future applications. Meanwhile, it is difficult to combine ultrasound and ES through traditional methods. Herein, a nanopatch consisting of an oriented barium titanate (BTO)‐incorporated polycaprolactone (PCL) nanofiber membrane for electricity generation and a layer of graphene oxide (GO)‐doped gelatin methacryloyl (GelMA) for neural interaction is developed. This band‐aid‐like BTO@PCL/GO@GelMA nanopatch has an excellent piezoelectric performance. In vitro, the nanopatches significantly promote axonal growth under LIPUS treatment. In a rat model of erectile dysfunction caused by peripheral nerve injury, the nanopatch is easily attached to a damaged nerve similar to a band‐aid. With the assistance of ultrasound, some mechanical energy is converted into electricity by the nanopatch, and synergistic neural stimulation of ultrasound and electricity is achieved. In this way, the nanopatch significantly promoted corpus cavernosum nerve repair, resulting in the improvement of tissue structure and erectile function as well as increased conception rate in female rats. In conclusion, the nanopatch offers a synergistic ultrasound‐ES for nerve repair easily and represents a novel strategy for peripheral nerve repair. [ABSTRACT FROM AUTHOR]

Objectives: For nerve injuries, not amendable to tensionless epineural coaptation of the nerve, autografts are the preferred treatment. Although absorbable sutures are not recommended for nerve repair, there is no evidence that non-absorbable sutures are superior to absorbable sutures. This study aims to assess the effectiveness of non-absorbable monofilament nylon sutures, absorbable monofilament vicryl sutures, and fibrin glue when used for nerve grafting. Methods: Lewis rats (N = 32) were subjected to a sciatic nerve transection and randomly assigned to a group: graft with Nylon, graft with Vicryl, graft with Fibrin Glue, or no graft. Motor function, sensory function, and thermal pain were assessed during a 12-week recovery period, and immunohistochemistry was used to assess macrophage response. Results: At 12 weeks, the Vicryl and Nylon groups had significantly larger ankle angles at to lift off, which is a measure of motor function, compared to injured controls (p < 0.05). Grafted rats displayed no difference in thermal response but hypersensitivity to mechanical stimuli compared to the uninjured hindlimb. The Nylon, Vicryl, and Fibrin Glue groups all had significantly less atrophy of the gastrocnemius muscle compared to injured controls (p < 0.0001). In the Fibrin Glue group, 3/9 grafts did not incorporate. The Nylon group had significantly less (p = 0.0004) axon growth surrounding the suture holes compared to the Vicryl group. There were no differences in the axon counts, motor neurons, or sensory neurons between all grafted rats. Conclusions: These results demonstrate that vicryl sutures work just as well as nylon for nerve recovery after injury and grafting. [ABSTRACT FROM AUTHOR]

Background: Traditionally known for bone regeneration, the Ilizarov technique's effectiveness in nerve reconstruction, particularly for extensive nerve damage, has yet to be widely recognized. Case presentation: This report presents a case study and proposes the innovative use of the Ilizarov technique for reconstructing extended nerve defects. In this study, we reviewed a 43‐year‐old male diagnosed with an open fracture of the right tibia combined with soft tissue injury resulting in a mangled injury in which a large part of his right tibial bone and nerve were lost. The patient was cured and the sensorimotor function was recovered after distraction osteogenesis by the Ilizarov technique, which is a unique application of this technique to repair a substantial long nerve defect, a rare occurrence in medical literature. It highlights the method of nerve lengthening, which is achieved by attaching the nerve stump to the bone stump. This approach allows for significant nerve regeneration and ensures a stable progression of the nerve, as the bone stump acts as a carrier, overcoming the challenges of direct nerve lengthening. Conclusions: The adaptability and effectiveness of the Ilizarov technique in a new area suggests the need to reconsider traditional approaches to complex nerve reconstruction. Placing this case within the context of current medical knowledge underscores the potential of this technique to revolutionize the treatment of extended nerve defects, offering hope for improved outcomes in challenging scenarios. [ABSTRACT FROM AUTHOR]

Successful nerve repair using bioadhesive hydrogels demands minimizing tissue–material interfacial mechanical mismatch to reduce immune responses and scar tissue formation. Furthermore, it is crucial to maintain the bioelectrical stimulation‐mediated cell‐signaling mechanism to overcome communication barriers within injured nerve tissues. Therefore, engineering bioadhesives for neural tissue regeneration necessitates the integration of electroconductive properties with tissue‐like biomechanics. In this study, we propose a stretchable bioadhesive based on a custom‐designed chemically modified elastin‐like polypeptides (ELPs) and a choline‐based bioionic liquid (Bio‐IL), providing an electroconductive microenvironment to reconnect damaged nerve tissue. The stretchability akin to native neural tissue was achieved by incorporating hydrophobic ELP pockets, and a robust tissue adhesion was obtained due to multi‐mode tissue–material interactions through covalent and noncovalent bonding at the tissue interface. Adhesion tests revealed adhesive strength ~10 times higher than commercially available tissue adhesive, Evicel®. Furthermore, the engineered hydrogel supported in vitro viability and proliferation of human glial cells. We also evaluated the biodegradability and biocompatibility of the engineered bioadhesive in vivo using a rat subcutaneous implantation model, which demonstrated facile tissue infiltration and minimal immune response. The outlined functionalities empower the engineered elastic and electroconductive adhesive hydrogel to effectively enable sutureless surgical sealing of neural injuries and promote tissue regeneration. [ABSTRACT FROM AUTHOR]

Background. The use of adipose tissue in reconstructive procedures has become popular in the last decades due to the adipose tissue properties of stem cells and mechanical protection. In acute nerve lesions, there have been experimental reports on the use of non-vascularised adipose tissue as an adjuvant for nerve recovery but to our knowledge there is no published research that describes the effect of the pedicled vascularised adipose tissue (pVAT) on acute nerve injuries. Therefore we decided to study the effect of pVAT on nerve regeneration when wrapped around an epineurial coaptation site and for a 5 mm defect of the sciatic nerve from the rat. Methods. The effect of pedicled vascularized adipose tissue (pVAT) on nerve regeneration was studied on the sciatic nerve injury model in twenty-four Wistar rats divided into four groups: epineurial repair; epineurial repair and pVAT; a 5 mm nerve gap bridged by an autograft; a 5 mm nerve gap bridged by a conduit-pVAT (C-pVAT). Automatization injuries, walking track analysis, postoperative extraneural fibrosis and histological analysis were performed three months after the intervention. Results. Although histological and functional nerve regeneration was present in various degrees in all the studied groups, nerve regeneration was not enhanced by the use of the pVAT or C-pVAT. The harvesting of the pVAT flap caused postoperative fibrosis when used as a conduit. Automutilation was not decreased by the use of the pVAT nor a correlation between automutilation and postoperative fibrosis in the studied groups could be established. The postoperative fibrosis did not influence neural regeneration in the pVAT and autograft group. Conclusion. Vascularized adipose tissue did not enhance neural regeneration when used as an adjunct procedure for primary nerve repair and or even as a novel conduit for 5 mm nerve defects in the rat sciatic nerve. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a central nerve injury that often leads to loss of motor and sensory functions at or below the level of the injury. Zebrafish have a strong ability to repair after SCI, but the role of microRNAs (miRNAs) after SCI remains unclear. Locomotor behavior analysis showed that adult zebrafish recovered about 30% of their motor ability at 2 weeks and 55% at 3 weeks after SCI, reflecting their strong ability to repair SCI. Through miRNA sequencing, mRNA sequencing, RT-qPCR experiment verification, and bioinformatics predictive analysis, the key miRNAs and related genes in the repair of SCI were screened. A total of 38 miRNAs were significantly different, the top ten miRNAs were verified by RT-qPCR. The prediction target genes were verified by the mRNAs sequencing results at the same time point. Finally, 182 target genes were identified as likely to be networked regulated by the 38 different miRNAs. GO and KEGG enrichment analysis found that miRNAs targeted gene regulation of many key pathways, such as membrane tissue transport, ribosome function, lipid binding, and peroxidase activity. The PPI network analysis showed that miRNAs were involved in SCI repair through complex network regulation, among which dre-miR-21 may enhance cell reversibility through nop56, and that dre-miR-125c regulates axon growth through kpnb1 to repair SCI. miRNAs promote neuronal survival and axon growth after SCI. The expression of dre-miR-21 was increased after SCI. Dre-miR-21 targets nop56 mRNA, which causes the Nop56 expression level to reduce, thus reducing the nuclei of ribosomal RNA methylation level, increasing the resistance of neurons, and promoting neuronal cell survival. The level of dre-miR-125c is increased after SCI, and dre-miR-125c targets kpnb1 mRNA and reduces the concentration of Kpnb1 at the axon site, thereby promoting axon outgrowth. At the same time, Kpnb1 is a retrograde signal protein of nerve injury, and reducing the expression level of Kpnb1 can inhibit cell death caused by excessive stress response. [ABSTRACT FROM AUTHOR]

Background Traditionally known for bone regeneration, the Ilizarov technique's effectiveness in nerve reconstruction, particularly for extensive nerve damage, has yet to be widely recognized. Case presentation This report presents a case study and proposes the innovative use of the Ilizarov technique for reconstructing extended nerve defects. In this study, we reviewed a 43‐year‐old male diagnosed with an open fracture of the right tibia combined with soft tissue injury resulting in a mangled injury in which a large part of his right tibial bone and nerve were lost. The patient was cured and the sensorimotor function was recovered after distraction osteogenesis by the Ilizarov technique, which is a unique application of this technique to repair a substantial long nerve defect, a rare occurrence in medical literature. It highlights the method of nerve lengthening, which is achieved by attaching the nerve stump to the bone stump. This approach allows for significant nerve regeneration and ensures a stable progression of the nerve, as the bone stump acts as a carrier, overcoming the challenges of direct nerve lengthening. Conclusions The adaptability and effectiveness of the Ilizarov technique in a new area suggests the need to reconsider traditional approaches to complex nerve reconstruction. Placing this case within the context of current medical knowledge underscores the potential of this technique to revolutionize the treatment of extended nerve defects, offering hope for improved outcomes in challenging scenarios.

Purpose: A systematic review to identify treatment approaches for the management of pain following peripheral nerve injury. Methods: A published literature search was performed for the concepts of peripheral nerve injury and pain management with related synonyms. The strategies were created using a combination of controlled vocabulary terms and keywords and were executed in Embase.com, Ovid-Medline All, and Scopus from database inception. Database searches were completed on August 22, 2023. Results: The initial search resulted in a total of 1,793 citations. In total, 724 duplicates were removed, leaving 1,069 unique citations remaining for analysis. This review excluded all papers that were not specific to pain following peripheral nerve injury. Case and cohort studies (n < 5) were also excluded. Thirty-two articles on pain management strategies after peripheral nerve injury remained, with years of publication ranging from 1981 to 2023. An additional four articles were identified by manual search. Of the 36 articles reviewed, 15 articles reported on the approach to the treatment of pain after a peripheral nerve injury, and the other 22 articles consisted of cohort and case series studies. Conclusions: There is a lack of literature describing efficacy of various treatment strategies for pain following peripheral nerve injuries. Few studies provide clear, stepwise clinical guidance for practicing physicians and other health care providers on the treatment of these complicated patients.

Purpose: Vascularized nerve grafts (VNGs) have been proposed as encouraging alternatives to conventional nerve grafting; however, there is ongoing debate regarding the clinical advantages of the approach compared with standard grafting. This review aims to gather and analyze reported cases of upper extremity nerve repair using VNGs documented in the published literature. Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed/MEDLINE, Embase, and Cochrane were searched. Inclusion criteria for this review included the following: (1) human subjects or cadaveric studies, (2) describing a vascularized nerve grafting procedure or suggesting a nerve and vascular supply for a potential vascularized nerve graft, and (3) upper extremity nerve repair in clinical studies. Results: Data were extracted from 45 clinical studies. Of 535 patients, the most common injury pattern was root avulsion and rupture (88.7%). The most utilized VNG was the ulnar nerve (72.8%), followed by nerve to long head of triceps (8.8%) and sural nerve (8.2%); most common recipients were median (57.6%), axillary (12.5%), and musculocutaneous nerves (11.9%). Between patients who had medical research council scale scores, 69% had functional (M3 and above) motor and 72.7% sensory (S3

Peripheral nerve surgeries are a complex undertaking that require a multifaceted team approach. For optimal outcomes, early involvement of therapy, planning with the surgical team, and communication with the patient are crucial. This facilitates compliance and is an integral component of the recovery process after these large procedures.

Peripheral nerve injuries can be devastating. Although neuropraxic and some axonotmesis injuries will recover spontaneously, nerve repair or reconstruction is required to restore function in high-grade axonotmesis or neurotmesis injuries. The first step of nerve repair or reconstruction is adequate nerve debridement with removal of necrotic and fibrous tissues. Debridement decreases neuroma formation at the repair site and produces an optimal surface for axonal regeneration. This article discusses nerve debridement, including the goals of debridement, debridement techniques, and signs of adequate nerve debridement before repair.

Effective nerve coaptation entails tensionless repair of healthy fascicles with intact fascicular architecture and a well-vascularized environment, supportive of the regenerative cellular behaviors of neurons, immune cells, and Schwann cells. Suture coaptations have historically been used to ensure that these criteria are met for end-to-end repair, nerve transfers, and allograft or autograft reconstructions; however, unfortunately, overall restoration of function remains poor. As optimal coaptation is required for return of sensorimotor function, adjunct biomaterials are increasingly being enlisted attempting to optimize these suture-based coaptations. The purpose of this review was to discuss the biological, preclinical, and clinical data for the use of fibrin glue and nerve wraps made of type 1 collagen, porcine small intestine submucosa, chitosan, and human amniotic membrane. This study provides available data on each material’s ability to optimize the regenerative potential of nerve repair as well as available outcomes data. Although each biomaterial discussed has benefits to nerve regeneration, at large, data remain heterogeneous, and continued investigation is required to fully understand the specific mechanisms involved and the long-term potential clinical impacts each can provide for improvement of sensorimotor outcomes.

Platelet-rich plasma (PRP) has the capability of assisting in the recovery of damaged tissues by releasing a variety of biologically active factors to initiate a hemostatic cascade reaction and promote the synthesis of new connective tissue and revascularization. It is now widely used for tissue engineering repair. In addition, PRP has demonstrated nerve repair and pain relief, and has been studied and applied to the facial nerve, median nerve, sciatic nerve, and central nerve.These suggest that PRP injection therapy has a positive effect on nerve repair. This indicates that PRP has high clinical value and potential application in nerve repair. It is worthwhile for scientists and medical workers to further explore and study PRP to expand its application in nerve repair, and to provide a more reliable scientific basis for the opening of a new approach to nerve repair.

Abstract Background As a common disabling disease, irreversible neuronal death due to spinal cord injury (SCI) is the root cause of functional impairment; however, the capacity for neuronal regeneration in the developing spinal cord tissue is limited. Therefore, there is an urgent need to investigate how defective neurons can be replenished and functionally integrated by neural regeneration; the reprogramming of intrinsic cells into functional neurons may represent an ideal solution. Methods A mouse model of transection SCI was prepared by forceps clamping, and an adeno-associated virus (AAV) carrying the transcription factors NeuroD1 and Neurogenin-2(Ngn2) was injected in situ into the spinal cord to specifically overexpress these transcription factors in astrocytes close to the injury site. 5-bromo-2´-deoxyuridine (BrdU) was subsequently injected intraperitoneally to continuously track cell regeneration, neuroblasts and immature neurons marker expression, neuronal regeneration, and glial scar regeneration. In addition, immunoprotein blotting was used to measure the levels of transforming growth factor-β (TGF-β) pathway-related protein expression. We also evaluated motor function, sensory function, and the integrity of the blood-spinal cord barrier(BSCB). Results The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord was achieved by specific AAV vectors. This intervention led to a significant increase in cell regeneration and the proportion of cells with neuroblasts and immature neurons cell properties at the injury site(p 0.05), although the treated mice had more sensory sensitivity and greater voluntary motor ability in open field than the non-intervention mice. We observed significant repair of the BSCB at the center of the injury site (p

Abstract Despite recent advancements in peripheral nerve regeneration, the creation of nerve conduits with chemical and physical cues to enhance glial cell function and support axonal growth remains challenging. This study aimed to assess the impact of electrical stimulation (ES) using a conductive nerve conduit on sciatic nerve regeneration in a rat model with transection injury. The study involved the fabrication of conductive nerve conduits using silk fibroin and Au nanoparticles (AuNPs). Collagen hydrogel loaded with green fluorescent protein (GFP)-positive adipose-derived mesenchymal stem cells (ADSCs) served as the filling for the conduit. Both conductive and non-conductive conduits were applied with and without ES in rat models. Locomotor recovery was assessed using walking track analysis. Histological evaluations were performed using H&E, luxol fast blue staining and immunohistochemistry. Moreover, TEM analysis was conducted to distinguish various ultrastructural aspects of sciatic tissue. In the ES + conductive conduit group, higher S100 (p

Background: As a common disabling disease, irreversible neuronal death due to spinal cord injury (SCI) is the root cause of functional impairment; however, the capacity for neuronal regeneration in the developing spinal cord tissue is limited. Therefore, there is an urgent need to investigate how defective neurons can be replenished and functionally integrated by neural regeneration; the reprogramming of intrinsic cells into functional neurons may represent an ideal solution. Methods: A mouse model of transection SCI was prepared by forceps clamping, and an adeno-associated virus (AAV) carrying the transcription factors NeuroD1 and Neurogenin-2(Ngn2) was injected in situ into the spinal cord to specifically overexpress these transcription factors in astrocytes close to the injury site. 5-bromo-2´-deoxyuridine (BrdU) was subsequently injected intraperitoneally to continuously track cell regeneration, neuroblasts and immature neurons marker expression, neuronal regeneration, and glial scar regeneration. In addition, immunoprotein blotting was used to measure the levels of transforming growth factor-β (TGF-β) pathway-related protein expression. We also evaluated motor function, sensory function, and the integrity of the blood-spinal cord barrier(BSCB). Results: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord was achieved by specific AAV vectors. This intervention led to a significant increase in cell regeneration and the proportion of cells with neuroblasts and immature neurons cell properties at the injury site(p < 0.0001). Immunofluorescence staining identified astrocytes with neuroblasts and immature neurons cell properties at the site of injury while neuronal marker-specific staining revealed an increased number of mature astrocytes at the injury site. Behavioral assessments showed that the intervention did not improve The BMS (Basso mouse scale) score (p = 0.0726) and gait (p > 0.05), although the treated mice had more sensory sensitivity and greater voluntary motor ability in open field than the non-intervention mice. We observed significant repair of the BSCB at the center of the injury site (p < 0.0001) and a significant improvement in glial scar proliferation. Electrophysiological assessments revealed a significant improvement in spinal nerve conduction (p < 0.0001) while immunostaining revealed that the levels of TGF-β protein at the site of injury in the intervention group were lower than control group (p = 0.0034); in addition, P70 s6 and PP2A related to the TGF-β pathway showed ascending trend (p = 0.0036, p = 0.0152 respectively). Conclusions: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord after spinal cord injury can reprogram astrocytes into neurons and significantly enhance cell regeneration at the injury site. The reprogramming of astrocytes can lead to tissue repair, thus improving the reduced threshold and increasing voluntary movements. This strategy can also improve the integrity of the blood-spinal cord barrier and enhance nerve conduction function. However, the simple reprogramming of astrocytes cannot lead to significant improvements in the striding function of the lower limbs. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury (PNI) is one of the most serious causes of disability and loss of work capacity of younger individuals. Although PNS has a certain degree of regeneration, there are still challenges like disordered growth, neuroma formation, and incomplete regeneration. Regarding the management of PNI, conventional methods such as surgery, pharmacotherapy, and rehabilitative therapy. Treatment strategies vary depending on the severity of the injury. While for the long nerve defect, autologous nerve grafting is commonly recognized as the preferred surgical approach. Nevertheless, due to lack of donor sources, neurological deficits and the low regeneration efficiency of grafted nerves, nerve guide conduits (NGCs) are recognized as a future promising technology in recent years. This review provides a comprehensive overview of current treatments for PNI, and discusses NGCs from different perspectives, such as material, design, fabrication process, and composite function. [ABSTRACT FROM AUTHOR]

Despite recent advancements in peripheral nerve regeneration, the creation of nerve conduits with chemical and physical cues to enhance glial cell function and support axonal growth remains challenging. This study aimed to assess the impact of electrical stimulation (ES) using a conductive nerve conduit on sciatic nerve regeneration in a rat model with transection injury. The study involved the fabrication of conductive nerve conduits using silk fibroin and Au nanoparticles (AuNPs). Collagen hydrogel loaded with green fluorescent protein (GFP)-positive adipose-derived mesenchymal stem cells (ADSCs) served as the filling for the conduit. Both conductive and non-conductive conduits were applied with and without ES in rat models. Locomotor recovery was assessed using walking track analysis. Histological evaluations were performed using H&E, luxol fast blue staining and immunohistochemistry. Moreover, TEM analysis was conducted to distinguish various ultrastructural aspects of sciatic tissue. In the ES + conductive conduit group, higher S100 (p < 0.0001) and neurofilament (p < 0.001) expression was seen after 6 weeks. Ultrastructural evaluations showed that conductive scaffolds with ES minimized Wallerian degeneration. Furthermore, the conductive conduit with ES group demonstrated significantly increased myelin sheet thickness and decreased G. ratio compared to the autograft. Immunofluorescent images confirmed the presence of GFP-positive ADSCs by the 6th week. Locomotor recovery assessments revealed improved function in the conductive conduit with ES group compared to the control group and groups without ES. These results show that a Silk/AuNPs conduit filled with ADSC-seeded collagen hydrogel can function as a nerve conduit, aiding in the restoration of substantial gaps in the sciatic nerve with ES. Histological and locomotor evaluations indicated that ES had a greater impact on functional recovery compared to using a conductive conduit alone, although the use of conductive conduits did enhance the effects of ES. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral nerve injury (PNI) is increasingly prevalent and challenging to treat despite advances in microsurgical techniques. In this context, adipose tissue derivatives, such as adipose-derived stem cells, nanofat, and stromal vascular fraction have been gaining attention as potential allies in peripheral nerve regeneration. Objectives: This study aims to explore the use of adipose tissue derivatives in nerve regeneration following peripheral nerve transection in murine models. Thus, we assess and synthesize the key techniques and methods used for evaluating the obtained nerve regeneration to guide future experimental research and clinical interventions. Methodology: A systematic review was conducted in February 2024, adhering to the Cochrane and PRISMA 2020 guidelines, using the PubMed, SciELO, and LILACS databases. The focus was on experimental studies involving adipose tissue derivatives in nerve regeneration in animal models post-transection. Only experimental trials reporting nerve regeneration outcomes were included; studies lacking a comparator group or evaluation methods were excluded. Results: Out of 273 studies initially identified from MEDLINE, 19 were selected for detailed analysis. The average study included 32.5 subjects, with about 10.2 subjects per intervention subgroup. The predominant model was the sciatic nerve injury with a 10 mm gap. The most common intervention involved unprocessed adipose-derived stem cells, utilized in 14 articles. Conclusions: This review underscores the significant potential of current methodologies in peripheral nerve regeneration, particularly highlighting the use of murine models and thorough evaluation techniques. [ABSTRACT FROM AUTHOR]

Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context, mesenchymal stem cell (MSC)-derived exosomes have emerged as a potential therapeutic option. Thus, the focus of this study was to review currently available data on MSC-derived exosome-mounted scaffolds in peripheral nerve regeneration in order to identify the most promising scaffolds and exosome sources currently in the field of peripheral nerve regeneration. We conducted a systematic review following PRISMA 2020 guidelines. Exosome origins varied (adipose-derived MSCs, bone marrow MSCs, gingival MSC, induced pluripotent stem cells and a purified exosome product) similarly to the materials (Matrigel, alginate and silicone, acellular nerve graft [ANG], chitosan, chitin, hydrogel and fibrin glue). The compound muscle action potential (CMAP), sciatic functional index (SFI), gastrocnemius wet weight and histological analyses were used as main outcome measures. Overall, exosome-mounted scaffolds showed better regeneration than scaffolds alone. Functionally, both exosome-enriched chitin and ANG showed a significant improvement over time in the sciatica functional index, CMAP and wet weight. The best histological outcomes were found in the exosome-enriched ANG scaffold with a high increase in the axonal diameter and muscle cross-section area. Further studies are needed to confirm the efficacy of exosome-mounted scaffolds in peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

Objective: To visualize and analyze the literature related to sciatic nerve injury treatment from January 2019 to December 2023, and summarize the current status, hotspots, and development trends of research in this field. Methods: Using CiteSpace and VOSviewer software, we searched the Web of Science database for literature related to the treatment of sciatic nerve injury. Then we analyzed and plotted visualization maps to show the number of publications, countries, institutions, authors, keywords, references, and journals. Results: A total of 2,653 articles were included in the English database. The annual number of publications exceeded 230, and the citation frequency increased yearly. The United States and China were identified as high-influence nations in this field. Nantong University was the leading institution in terms of close cooperation among institutions. The authors Wang Yu had the highest number of publications and were highly influential in this field. Keyword analysis and reference Burst revealed a research focus on nerve regeneration and neuropathic pain, which involve regenerative medicine and neural tissue engineering. Chronic pain resulting from sciatic nerve injury often manifests alongside anxiety, depression, cognitive-behavioral disorders, and other issues. Interventions such as stem cells, electrical stimulation, electroacupuncture, total joint replacement, pharmacological interventions, gene therapy, nerve conduits, chitosan scaffolds, and exercise promote nerve repair and alleviate pain. Schwann cells have been the focus of much attention in nerve repair and regeneration. Improving the outcome of sciatic nerve injury is a current research challenge and focus in this field. Based on keyword Burst, nerve conduits and grafts may become a potential research hotspot in the treatment of sciatic nerve injury. Conclusion: This visual analysis summarizes research trends and developments of sciatic nerve injury treatment and predicts potential research frontiers and hot directions. [ABSTRACT FROM AUTHOR]

Background: Adjunctive pharmacological treatment may improve nerve regeneration. We investigated nerve regeneration processes of PXL01 – a lactoferrin-derived peptide – after repair of the sciatic nerve in healthy Wistar rats. Materials & methods: PXL01, sodium hyaluronate (carrier) or sodium chloride was administered around the repair. After 6 days axonal outgrowth, Schwann cell response, pan- (CD68) and pro-healing (CD206) macrophages in sciatic nerve, sensory neuronal response in dorsal root ganglia (DRG) and expression of heat shock protein 27 (HSP27) in sciatic nerves and DRGs were analyzed. Results: Despite a lower number of pan-macrophages, other investigated variables in sciatic nerves or DRGs did not differ between the treatment groups. Conclusion: PLX01 applied locally inhibits inflammation through pan-macrophages in repaired sciatic nerves without any impact on nerve regeneration or pro-healing macrophages. Graphical Abstract Author highlights Local application of PXL01 decreases inflammation in the injured and immediate repaired nerve without changing the polarization of the macrophages. Local application of PXL01 does not improve or have any negative effect on nerve regeneration. Local application of PXL01 does not alter Schwann cell activity or neuroprotective effect of HSP27 in the injured and repaired nerve or in the sensory neurons. Hyaluronate, the PXL01 vehicle, does not alter nerve regeneration and has no effect on inflammation. CD206, known as antimannose receptor antibody, also stains the paranodal region in the contralateral-uninjured nerve. Results imply that PXL01 treatment can be used to treat scarred and tethered nerves, one of the defined neuromas after surgery, without a negative effect on the regeneration processes. [ABSTRACT FROM AUTHOR]

Distal nerve transfer is a refined surgical technique involving the redirection of healthy sacrificable nerves from one part of the body to reinstate function in another area afflicted by paralysis or injury. This approach is particularly valuable when the original nerves are extensively damaged and standard repair methods, such as direct suturing or grafting, may be insufficient. As the nerve coaptation is close to the recipient muscles or skin, distal nerve transfers reduce the time to reinnervation. The harvesting of nerves for transfer should usually result in minimal or no donor morbidity, as any anticipated loss of function is compensated for by adjacent muscles or overlapping cutaneous territory. Recent years have witnessed notable progress in nerve transfer procedures, markedly enhancing the outcomes of upper limb reconstruction for conditions encompassing peripheral nerve, brachial plexus and spinal cord injuries. [ABSTRACT FROM AUTHOR]

BackgroundPeripheral nerve injuries (PNIs) are associated with significant physical and psychological challenges, impacting both functional recovery and quality of life. Despite the physical focus of traditional treatments, psychological factors play a crucial role in the outcomes of PNI repair and recovery.ObjectivesThis systematic review aims to evaluate the impact of psychological and social factors on the repair and recovery of peripheral nerve injuries.MethodsA comprehensive literature search was conducted in PubMed/Medline, EMBASE, and Cochrane databases, covering studies from January 1985 to December 2022. A total of 36,190 records were identified, and after screening with Rayyan AI and applying inclusion criteria, 111 articles were selected for review.ResultsThe review highlights that pre-existing psychological conditions, as well as psychological responses to the injury and treatment, significantly influence recovery outcomes in PNI patients. Psychological interventions, when integrated into standard care, may improve functional recovery and quality of life.ConclusionsPsychosocial factors are critical in the management of PNIs and should be incorporated into treatment algorithms to enhance patient outcomes. Future research should focus on developing and integrating psychological support strategies in PNI treatment protocols.

Abstract Successful nerve repair using bioadhesive hydrogels demands minimizing tissue–material interfacial mechanical mismatch to reduce immune responses and scar tissue formation. Furthermore, it is crucial to maintain the bioelectrical stimulation‐mediated cell‐signaling mechanism to overcome communication barriers within injured nerve tissues. Therefore, engineering bioadhesives for neural tissue regeneration necessitates the integration of electroconductive properties with tissue‐like biomechanics. In this study, we propose a stretchable bioadhesive based on a custom‐designed chemically modified elastin‐like polypeptides (ELPs) and a choline‐based bioionic liquid (Bio‐IL), providing an electroconductive microenvironment to reconnect damaged nerve tissue. The stretchability akin to native neural tissue was achieved by incorporating hydrophobic ELP pockets, and a robust tissue adhesion was obtained due to multi‐mode tissue–material interactions through covalent and noncovalent bonding at the tissue interface. Adhesion tests revealed adhesive strength ~10 times higher than commercially available tissue adhesive, Evicel®. Furthermore, the engineered hydrogel supported in vitro viability and proliferation of human glial cells. We also evaluated the biodegradability and biocompatibility of the engineered bioadhesive in vivo using a rat subcutaneous implantation model, which demonstrated facile tissue infiltration and minimal immune response. The outlined functionalities empower the engineered elastic and electroconductive adhesive hydrogel to effectively enable sutureless surgical sealing of neural injuries and promote tissue regeneration.

Background. The use of adipose tissue in reconstructive procedures has become popular in the last decades due to the adipose tissue properties of stem cells and mechanical protection. In acute nerve lesions, there have been experimental reports on the use of non-vascularised adipose tissue as an adjuvant for nerve recovery but to our knowledge there is no published research that describes the effect of the pedicled vascularised adipose tissue (pVAT) on acute nerve injuries. Therefore we decided to study the effect of pVAT on nerve regeneration when wrapped around an epineurial coaptation site and for a 5 mm defect of the sciatic nerve from the rat. Methods. The effect of pedicled vascularized adipose tissue (pVAT) on nerve regeneration was studied on the sciatic nerve injury model in twenty-four Wistar rats divided into four groups: epineurial repair; epineurial repair and pVAT; a 5 mm nerve gap bridged by an autograft; a 5 mm nerve gap bridged by a conduit-pVAT (C-pVAT). Automatization injuries, walking track analysis, postoperative extraneural fibrosis and histological analysis were performed three months after the intervention. Results. Although histological and functional nerve regeneration was present in various degrees in all the studied groups, nerve regeneration was not enhanced by the use of the pVAT or C-pVAT. The harvesting of the pVAT flap caused postoperative fibrosis when used as a conduit. Automutilation was not decreased by the use of the pVAT nor a correlation between automutilation and postoperative fibrosis in the studied groups could be established. The postoperative fibrosis did not influence neural regeneration in the pVAT and autograft group. Conclusion. Vascularized adipose tissue did not enhance neural regeneration when used as an adjunct procedure for primary nerve repair and or even as a novel conduit for 5 mm nerve defects in the rat sciatic nerve.

Schwann cells (SCs) are the primary glia of the peripheral nervous system. SCs are involved in many debilitating disorders, including diabetic peripheral neuropathy (DPN). Here, we present a strategy for deriving SCs from human pluripotent stem cells (hPSCs) that enables comprehensive studies of SC development, physiology, and disease. hPSC-derived SCs recapitulate the molecular features of primary SCs and are capable of in vitro and in vivo myelination. We established a model of DPN that revealed the selective vulnerability of SCs to high glucose. We performed a high-throughput screen and found that an antidepressant drug, bupropion, counteracts glucotoxicity in SCs. Treatment of hyperglycemic mice with bupropion prevents their sensory dysfunction, SC death, and myelin damage. Further, our retrospective analysis of health records revealed that bupropion treatment is associated with a lower incidence of neuropathy among diabetic patients. These results highlight the power of this approach for identifying therapeutic candidates for DPN.

Objective Common peroneal nerve (CPN) injury is a frequently encountered lower extremity injury. Furthermore, several previous studies have demonstrated that patients who underwent direct suturing of the CPN following rupture experienced unfavorable postoperative prognoses. Therefore, we aimed to present a novel modified surgical approach for CPN rupture and assess the effectiveness of this technique in restoring lower limb functionality. Methods In this retrospective observational study, we included patients with CPN rupture who underwent one‐stage neurorrhaphy and posterior transposition combined with nerve wrapping using a gastrocnemius fascial flap for CPN rupture between January 2016 and December 2020. Lower limb function was evaluated using the lower extremity functional scale (LEFS) and British Medical Research Council (BMRC) grading system. We also assessed the influence of age, sex, duration of symptoms, mechanism of injury, and surgical modality on the postoperative recovery of lower extremity function using subgroup and regression analyses. Results Thirty‐seven patients (mean age = 35.76 ± 13.01 years) with at least 2 years of follow‐up were included in the final analysis. The LEFS scores significantly improved after surgery at the last follow‐up (p

BACKGROUND: Although nerve conduits provide an effective treatment approach for nerve repair, traditional nerve conduits merely serve as mechanical channels in the repair process. The therapeutic effect still needs to be improved. Carbon nanomaterials have good physicochemical properties and hold great potential in fields such as electrochemistry and tissue engineering. Nerve conduits loaded with carbon nanomaterials, after appropriate functional modifications, are expected to further enhance the quality of nerve repair. OBJECTIVE: To review the recent research progress of carbon nanomaterial-loaded nerve conduits/scaffolds for peripheral nerve repair. METHODS: PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for the literature on the application of carbon nanomaterial catheters in peripheral nerve regeneration. English keywords were “carbon nanomaterials, carbon-based nanomaterials, nerve conduit, nerve guidance conduit, scaffold, nerve regeneration, peripheral nerve repair, peripheral nerve injury” and Chinese keywords were “carbon nanomaterials, carbon materials, graphene, carbon nanotubes, nerve conduits, nerve scaffolds, nerve repair, nerve regeneration, peripheral nerve injury”. Finally, 69 articles were selected for this review. RESULTS AND CONCLUSION: (1) Carbon nanomaterials primarily restore damaged neural bioelectric signal conduction by activating calcium ion channels and inducing intracellular calcium activity. The application of various nerve conduit design strategies has improved the effectiveness of nerve repair. (2) Successful intraneural vascularization is the prerequisite for repairing peripheral nerve injuries. Reactive oxygen species and reactive nitrogen species generated by carbon nanomaterials trigger subsequent signaling pathways that promote intraneural vascularization. (3) The ratio of M1 to M2 macrophages affects the repair of peripheral nerve injuries. Carbon nanomaterials promote the polarization of macrophages into the M2 phenotype, thereby exerting their anti-inflammatory and regenerative effects. (4) Some carbon nanomaterials may induce excessive generation of reactive oxygen species intracellularly, potentially exhibiting cytotoxicity detrimental to nerve repair. However, appropriate functional modifications can improve the adverse effects caused by carbon nanomaterials. (5) Although carbon nanomaterials can restore the microenvironment of peripheral nerve injuries and play a positive role in promoting peripheral nerve regeneration, their inherent cytotoxicity and unclear in vivo degradation pathways still pose challenges for clinical application. However, by employing methods such as functional modification, it is possible to enhance the biocompatibility of carbon nanomaterials. Modified carbon nanomaterials have promising prospects in the field of neural tissue engineering. [ABSTRACT FROM AUTHOR]

Background: Simulating the post-traumatic continuity defect of small human peripheral nerves, we compared the effectiveness of fibrin glue with neurorrhaphy for nerve gap restoration. Methods: In twenty-four male Wistar rats, a fifteen mm defect in one sciatic nerve only was made and immediately repaired with an inverted polarity autograft. According to the used technique, rats were divided into Group A (Control), using traditional neurorrhaphy, and Group B (Study), using fibrine glue sealing; in total, 50% of rats were sacrificed at 16 weeks and 50% at 21 weeks. Before sacrifice, an assessment of motor function was done through Walking Track Analysis and an electroneurophysiological evaluation. After sacrifice, selected muscle mass indexes and the histology of the regenerated nerves were assessed. All data were evaluated by Student's t test for unpaired data. Results: No significant differences were found between the two groups, with only the exception of a relative improvement in the tibialis anterior muscle's number of motor units in the study group. Conclusion: Despite the fact that the use of fibrin glue as a nerve sealant is not superior in terms of functional recovery, its effectiveness is comparable to that of microsurgical repair. Hence, the faster and technically easier glueing technique could deserve broader clinical application. [ABSTRACT FROM AUTHOR]

The field of peripheral nerve regeneration is a dynamic and rapidly evolving area of research that continues to captivate the attention of neuroscientists worldwide. The quest for effective treatments and therapies to enhance the healing of peripheral nerves has gained significant momentum in recent years, as evidenced by the substantial increase in publications dedicated to this field. This surge in interest reflects the growing recognition of the importance of peripheral nerve recovery and the urgent need to develop innovative strategies to address nerve injuries. In this context, this article aims to contribute to the existing knowledge by providing a comprehensive review that encompasses both biomaterial and clinical perspectives. By exploring the utilization of nerve guidance conduits and pharmacotherapy, this article seeks to shed light on the remarkable advancements made in the field of peripheral nerve regeneration. Nerve guidance conduits, which act as artificial channels to guide regenerating nerves, have shown promising results in facilitating nerve regrowth and functional recovery. Additionally, pharmacotherapy approaches have emerged as potential avenues for promoting nerve regeneration, with various therapeutic agents being investigated for their neuroprotective and regenerative properties. The pursuit of advancing the field of peripheral nerve regeneration necessitates persistent investment in research and development. Continued exploration of innovative treatments, coupled with a deeper understanding of the intricate processes involved in nerve regeneration, holds the promise of unlocking the complete potential of these groundbreaking interventions. By fostering collaboration among scientists, clinicians, and industry partners, we can accelerate progress in this field, bringing us closer to the realization of transformative therapies that restore function and quality of life for individuals affected by peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts. The healing process of PNI is frequently accompanied by not only axonal and myelination regeneration but also angiogenesis, which initializes nerve regeneration through vascular endothelial growth factor A (VEGF-A). In this study, a composite nerve conduit with a poly (lactic-co-glycolic acid) (PLGA) hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with VEGF-A transfected Schwann cells (SCs) as the inner layer was established to evaluate its promising ability for peripheral nerve repair. A rat model of peripheral nerve defect was used to examine the efficiency of PLGA/GelMA-SC (VA) conduits, whereas autograft, PLGA, PLGA/GelMA, and PLGA/GelMA-SC (NC) were used as controls. VEGF-A-transfected SCs can provide a stable source for VEGF-A secretion. Furthermore, encapsulation in GelMA cannot only promote proliferation and tube formation of human umbilical vein endothelial cells but also enhance dorsal root ganglia and neuronal cell extension. Previous animal studies have demonstrated that the regenerative effects of PLGA/GelMA-SC (VA) nerve conduit were similar to those of autografts and much better than those of other conduits. These findings indicate that combination of VEGF-A-overexpressing SCs and PLGA/GelMA conduit-guided peripheral nerve repair provides a promising method that enhances angiogenesis and regeneration during nerve repair. Nerve guidance conduits shows promise for peripheral nerve repair, while achieving the repair efficiency of autografts remains a challenge. In this study, a composite nerve conduit with a PLGA hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with vascular endothelial growth factor A (VEGF-A)-transfected Schwann cells (SCs) as the inner layer was established to evaluate its potential ability for peripheral nerve repair. This approach preserves growth factor bioactivity and enhances material properties. GelMA insertion promotes Schwann cell proliferation and morphology extension. Moreover, transfected SCs serve as a stable VEGF-A source and fostering angiogenesis. This study offers a method preserving growth factor efficacy and safeguarding SCs, providing a comprehensive solution for enhanced angiogenesis and nerve regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Common peroneal nerve (CPN) injury is a frequently encountered lower extremity injury. Furthermore, several previous studies have demonstrated that patients who underwent direct suturing of the CPN following rupture experienced unfavorable postoperative prognoses. Therefore, we aimed to present a novel modified surgical approach for CPN rupture and assess the effectiveness of this technique in restoring lower limb functionality. Methods: In this retrospective observational study, we included patients with CPN rupture who underwent one‐stage neurorrhaphy and posterior transposition combined with nerve wrapping using a gastrocnemius fascial flap for CPN rupture between January 2016 and December 2020. Lower limb function was evaluated using the lower extremity functional scale (LEFS) and British Medical Research Council (BMRC) grading system. We also assessed the influence of age, sex, duration of symptoms, mechanism of injury, and surgical modality on the postoperative recovery of lower extremity function using subgroup and regression analyses. Results: Thirty‐seven patients (mean age = 35.76 ± 13.01 years) with at least 2 years of follow‐up were included in the final analysis. The LEFS scores significantly improved after surgery at the last follow‐up (p < 0.01). Moreover, 67.57% of the patients achieved good or excellent postoperative outcomes (BMRC: M3 or above). Results of the subgroup analysis and regression models suggested that patients who underwent direct suturing showed better recovery of lower extremity function than those who underwent nerve grafting. Conclusion: One‐stage neurorrhaphy and posterior transposition combined with nerve wrapping using a gastrocnemius fascial flap exhibited encouraging outcomes in restoring lower‐limb function among patients with CPN rupture. This novel surgical technique is expected to be an effective method for treating CPN ruptures in the future. [ABSTRACT FROM AUTHOR]

Microsuture neurorrhaphy is technically challenging and has inherent drawbacks. This study evaluated the potential of a novel, sutureless nerve coaptation device to improve efficiency and precision. Twelve surgeons participated in this study—six attending hand/microsurgeons and six trainees (orthopedic and plastic surgery residents or hand surgery fellows). Twenty-four cadaver arm specimens were used, and nerve repairs were performed at six sites in each specimen—the median and ulnar nerves in the proximal forearm, the median and ulnar nerves in the distal forearm, and the common digital nerves to the second and third web spaces. Each study participant performed nerve repairs at all six injury locations in two different cadaver arms (n = 12 total repairs for each participating surgeon). The nerve repairs were timed, tested for tensile strength, and graded for alignment and technical repair quality. A substantial reduction in time was required to perform repairs with the novel coaptation device (1.6 ± 0.8 minutes) compared with microsuture (7.2 ± 3.6 minutes). Device repairs were judged clinically acceptable (scoring "Excellent" or "Good" by most of the expert panel) in 97% of the repairs; the percentage of suture repairs receiving Excellent/Good scores by most of the expert panel was 69.4% for attending surgeons and 36.1% for trainees. The device repairs exhibited a higher average peak tensile force (7.0 ± 3.6 N) compared with suture repairs (2.6 ± 1.6 N). Nerve repairs performed with a novel repair device were performed faster and with higher technical precision than those performed using microsutures. Device repairs had substantially greater tensile strength than microsuture repairs. The evaluated novel nerve repair device may improve surgical efficiency and nerve repair quality. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral nerves are frequently affected by lesions caused by traumatic or iatrogenic damages, resulting in loss of motor and sensory function, crucial in orthopedic outcomes and with a significant impact on patients' quality of life. Many strategies have been proposed over years to repair nerve injuries with substance loss, to achieve musculoskeletal reinnervation and functional recovery. Allograft have been tested as an alternative to the gold standard, the autograft technique, but nerves from donors frequently cause immunogenic response. For this reason, several studies are focusing to find the best way to decellularize nerves preserving either the extracellular matrix, either the basal lamina, as the key elements used by Schwann cells and axons during the regenerative process. Methods: This study focuses on a novel decellularization protocol for porcine nerves, aimed at reducing immunogenicity while preserving essential elements like the extracellular matrix and basal lamina, vital for nerve regeneration. To investigate the efficacy of the decellularization protocol to remove immunogenic cellular components of the nerve tissue and to preserve the basal lamina and extracellular matrix, morphological analysis was performed through Masson's Trichrome staining, immunofluorescence, high resolution light microscopy and transmission electron microscopy. Decellularized porcine nerve graft were then employed in vivo to repair a rat median nerve lesion. Morphological analysis was also used to study the ability of the porcine decellularized graft to support the nerve regeneration. Results and Discussion: The decellularization method was effective in preparing porcine superficial peroneal nerves for grafting as evidenced by the removal of immunogenic components and preservation of the ECM. Morphological analysis demonstrated that four weeks after injury, regenerating fibers colonized the graft suggesting a promising use to repair severe nerve lesions. The idea of using a porcine nerve graft arises from a translational perspective. This approach offers a promising direction in the orthopedic field for nerve repair, especially in severe cases where conventional methods are limited. [ABSTRACT FROM AUTHOR]

Simple Summary: Peripheral nerve injuries are common in the clinical setting and may affect functionality by permanent monoplegia that could end in amputation. Electrical stimulation is an option to help recovery, in addition to exercises and locomotor training with a positive synergetic effect on nerve regeneration. These approaches could benefit from other rehabilitation techniques, such as laser and ultrasounds, as well as cell-based therapies, considering a One Health perspective. Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, from a One Health perspective. This review offers a hands-on vision of the non-invasive and conservative approaches to peripheral nerve injury, focusing on the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation of BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities (low-level laser therapy, ultrasounds, pulsed electromagnetic fields, electroacupuncture and others). In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoid situations of permanent monoplegic limbs that could lead to amputation. [ABSTRACT FROM AUTHOR]

Introduction: Spinal cord injury (SCI) is associated with microenvironment imbalance, thereby resulting in poor regeneration and recovery of the spinal cord. Gene therapy can be used to balance the inflammatory response, however target genes cannot exist in localized injured areas.Methods: A genetically engineered electrospun scaffold (GEES) to achieve long-term immunoregulation and nerve repair was constructed. By combining the microfluidic and electrospinning techniques, interleukin-10 plasmid (pIL10) was loaded into lipid nanoparticles (LNPs) (pIL10-LNP), which was encapsulated to the nerve growth factor (NGF). Immunofluorescence staining, qRT-PCR, ELISA, flow cytometry, and other tests were employed to comprehensively assess the role of GEES in modulating macrophage polarization and facilitating neural repair.Results: The results showed that the scaffold released >70% of the pIL10-LNP within 10 d and continued slow release within 30 d. In vitro cell experiments have demonstrated that GEES effectively stimulates macrophages to secrete anti-inflammatory cytokines and facilitates the differentiation of neural stem cells into neuronal cells. In rat T9 SCI model, the GEES significantly inhibited the inflammatory response in the acute and chronic phases of SCI by transfecting local tissues with slow-release pIL10-LNP to promote the release of the anti-inflammatory factor IL10, thereby creating a favorable microenvironment. With the addition of NGF, the repair and regeneration of nerve tissues was effectively promoted, and the post-SCI motor function of rats improved.Discussion: GEES can regulate post-SCI immune responses through continuous and effective gene delivery, providing a new strategy for the construction of electrospun scaffolds for nerve repair in gene therapy.

Abstract Background This study aims to assess the recovery patterns and factors influencing outcomes in patients with common peroneal nerve (CPN) injury. Methods This retrospective study included 45 patients with CPN injuries treated between 2009 and 2019 in Jing’an District Central Hospital. The surgical interventions were categorized into three groups: neurolysis (group A; n = 34 patients), nerve repair (group B; n = 5 patients) and tendon transfer (group C; n = 6 patients). Preoperative and postoperative sensorimotor functions were evaluated using the British Medical Research Council grading system. The outcome of measures included the numeric rating scale, walking ability, numbness and satisfaction. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal time interval between injury and surgery for predicting postoperative foot dorsiflexion function, toe dorsiflexion function, and sensory function. Results Surgical interventions led to improvements in foot dorsiflexion strength in all patient groups, enabling most to regain independent walking ability. Group A (underwent neurolysis) had significant sensory function restoration (P

Background: Peripheral nerve injuries (PNIs) of the upper limb are very common events within the pediatric population, especially following soft tissue trauma and bone fractures. Symptoms of brachial plexus nerve injuries can differ considerably depending on the site and severity of injury. Compared to median and radial nerves, the ulnar nerve (UN) is the most frequently and severely injured nerve of the upper extremity. Indeed, due to its peculiar anatomical path, the UN is known to be particularly vulnerable to traumatic injuries, which result in pain and substantial motor and sensory disabilities of the forearm and hand. Therefore, timely and appropriate postoperative management of UN lesions is crucial to avoid permanent sensorymotor deficits and claw hand deformities leading to lifelong impairments. Nevertheless, the literature regarding the rehabilitation following PNIs is limited and lacks clear evidence regarding a solid treatment algorithm for the management of UN lesions that ensures full functional recovery. Case presentation: The patient is a 11-year-old child who experienced left-hand pain, stiffness, and disability secondary to a domestic accident. The traumatic UN lesion occurred about 8 cm proximal to Guyon's canal and it was surgically treated with termino-terminal (end-to-end) neurorrhaphy. One month after surgery, the patient underwent multimodal rehabilitative protocol and both subjective and functional measurements were recorded at baseline (T0) and at 3- (T1) and 5-month (T2) follow-up. At the end of the rehabilitation protocol, the patient achieved substantial reduction in pain and improvement in quality of life. Of considerable interest, the patient regained a complete functional recovery with satisfactory handgrip and pinch functions in addition with a decrease of disability in activities of daily living. Conclusion: A timely and intensive rehabilitative intervention done by qualified hand therapist with previous training in the rehabilitation of upper limb neuromuscular disorders is pivotal to achieve a stable and optimal functional recovery of the hand, while preventing the onset of deformities, in patients with peripheral nerve injuries of the upper limb. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess the recovery patterns and factors influencing outcomes in patients with common peroneal nerve (CPN) injury. Methods: This retrospective study included 45 patients with CPN injuries treated between 2009 and 2019 in Jing'an District Central Hospital. The surgical interventions were categorized into three groups: neurolysis (group A; n = 34 patients), nerve repair (group B; n = 5 patients) and tendon transfer (group C; n = 6 patients). Preoperative and postoperative sensorimotor functions were evaluated using the British Medical Research Council grading system. The outcome of measures included the numeric rating scale, walking ability, numbness and satisfaction. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal time interval between injury and surgery for predicting postoperative foot dorsiflexion function, toe dorsiflexion function, and sensory function. Results: Surgical interventions led to improvements in foot dorsiflexion strength in all patient groups, enabling most to regain independent walking ability. Group A (underwent neurolysis) had significant sensory function restoration (P < 0.001), and three patients in Group B (underwent nerve repair) had sensory improvements. ROC analysis revealed that the optimal time interval for achieving M3 foot dorsiflexion recovery was 9.5 months, with an area under the curve (AUC) of 0.871 (95% CI = 0.661–1.000, P = 0.040). For M4 foot dorsiflexion recovery, the optimal cut-off was 5.5 months, with an AUC of 0.785 (95% CI = 0.575–0.995, P = 0.020). When using M3 toe dorsiflexion recovery or S4 sensory function recovery as the gold standard, the optimal cut-off remained at 5.5 months, with AUCs of 0.768 (95% CI = 0.582–0.953, P = 0.025) and 0.853 (95% CI = 0.693–1.000, P = 0.001), respectively. Conclusions: Our study highlights the importance of early surgical intervention in CPN injury recovery, with optimal outcomes achieved when surgery is performed within 5.5 to 9.5 months post-injury. These findings provide guidance for clinicians in tailoring treatment plans to the specific characteristics and requirements of CPN injury patients. [ABSTRACT FROM AUTHOR]

Oxygen is compulsory for mitochondrial function and energy supply, but it has numerous more nuanced roles. The different roles of oxygen in peripheral nerve regeneration range from energy supply, inflammation, phagocytosis, and oxidative cell destruction in the context of reperfusion injury to crucial redox signaling cascades that are necessary for effective axonal outgrowth. A fine balance between reactive oxygen species production and antioxidant activity draws the line between physiological and pathological nerve regeneration. There is compelling evidence that redox signaling mediated by the Nox family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases plays an important role in peripheral nerve regeneration. Further research is needed to better characterize the role of Nox in physiological and pathological circumstances, but the available data suggest that the modulation of Nox activity fosters great therapeutic potential. One of the promising approaches to enhance nerve regeneration by modulating the redox environment is hyperbaric oxygen therapy. In this review, we highlight the influence of various oxygenation states, i.e., hypoxia, physoxia, and hyperoxia, on peripheral nerve repair and regeneration. We summarize the currently available data and knowledge on the effectiveness of using hyperbaric oxygen therapy to treat nerve injuries and discuss future directions. [ABSTRACT FROM AUTHOR]