Schwann Cell Growth Research Articles

Oriented artificial nanofibers and laser induced periodic surface structures as substrates for Schwann cells alignment.

People with injuries to the peripheral nervous system suffer from paralysis of the facial muscles, fingers and hands or toes and feet, often for the rest of their lives, due to its poor functional regeneration. Therefore, to improve patients' quality of life, there is an urgent need for conduits that effectively support the healing of large defects in nerve pathways through specific guidance of nerve cells. This paper describes two specific methods for achieving directed growth of Schwann cells, a type of glial cells that can support the regeneration of the nerve pathway by guiding the neuronal axons in the direction of their alignment. One method uses aligned polyamide-6 (PA-6) nanofibers produced via electrospinning on a very fast rotating structured collector, which enables easy nanofiber detachment, without additional effort. The other method implies the exposure of a poly(ethylene terephthalate) (PET) foil to a KrF* laser beam, that renders a nanorippled surface topography. Schwann cell growth on these substrates was inspected after one week of cultivation by means of scanning electron microscopy (SEM). For both methods we show that Schwann cells grow in a certain direction, predetermined by nanofiber and nanoripple orientation. In contrast, cells cultivated on randomly oriented nanofibers or unstructured surfaces, show an omnidirectional growth behavior. These two methods can be used to produce nerve conduits for the treatment of injuries to the peripheral nervous system.

Melittin promotes the proliferation of Schwann cells in hyperglycemic environment by up‑regulating the Crabp2/Wnt/β‑catenin signaling pathway.

The present study aimed to explore the effect of melittin (MLT) on the growth of Schwann cells (SCs) in high glucose conditions and to understand the mechanisms involved. The goal was to provide a theoretical basis for using MLT in the treatment of diabetic peripheral neuropathy (DPN). The CCK‑8 assay was used to measure cell activity at different concentrations of glucose and MLT. Flow cytometry was employed to analyze the effect of MLT on cell cycle phases and apoptosis in SCs under high glucose conditions. To identify differentially expressed proteins, 4D label‑free quantitative proteomics with liquid chromatography‑mass spectrometry was used, followed by biological analysis to explore potential mechanisms. PCR, western blotting and immunofluorescence were conducted to confirm these mechanisms. Melittin (0.2 µg/ml) increased the proliferation of SCs in a high glucose environment. Flow cytometry showed that after MLT treatment, the proportion of cells in the G2/M+S phase increased and the combined ratio of early and late apoptosis decreased under high glucose conditions. Proteomics identified 1,784 proteins with significant changes in expression; 725 were upregulated, and 1,059 were downregulated. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the differentially expressed proteins were mainly involved in metabolic pathways and neurodegenerative disease pathways. PCR, western blotting and immunofluorescence confirmed the increase in Crabp2, Wnt3a, C‑Jun, CDK4, CyclinD1 and proliferating cell nuclear antigen. In high glucose conditions, MLT protects SCs from glucose toxicity by upregulating the Crabp2/Wnt/β‑catenin signaling pathway, potentially providing a new treatment for DPN.

Oriented artificial nanofibers and laser induced periodic surface structures as substrates for Schwann cells alignment

People with injuries to the peripheral nervous system, due to its poor functional regeneration, suffer from paralysis of the facial muscles, fingers and hands, or toes and feet, often for the rest of their lives. Therefore, to improve patients’ quality of life, there is an urgent need for conduits that effectively support the healing of large defects in nerve pathways through specific guidance of nerve cells. This paper describes two specific methods for achieving directed growth of Schwann cells, a type of glial cells that can support the regeneration of the nerve pathway by guiding the neuronal axons in the direction of their alignment. One method implies the exposure of a poly(ethylene terephthalate) (PET) foil to a KrF* laser beam, that renders a nanorippled surface topography. The other method uses aligned polyamide-6 (PA-6) nanofibers produced via electrospinning on a very fast rotating structured collector, which enables easy nanofiber detachment, without additional effort. Schwann cells growth on these substrates was inspected after one week of cultivation by means of scanning electron microscope (SEM). For both methods we show that Schwann cells grow in a certain direction, predetermined by nanoripples and nanofibers orientation. In contrast, cells cultivated onto unstructured surfaces or randomly oriented nanofibers, show an omnidirectional growth behavior.

Anisotropic topological scaffolds synergizing non-invasive wireless magnetic stimulation for accelerating long-distance peripheral nerve regeneration

Long-distance peripheral nerve regeneration is the challenging clinical problem that needs to be resolved urgently. In this study, an anisotropic topological Chitosan@Artemisia sphaerocephala (CS@AS) scaffold containing Fe3O4 nanoparticles for achieving non-invasive wireless magnetic stimulation on nerve regeneration process under external static magnetic field (SMF) was developed using surface modification and micro-molding method, aiming to provide a synergistic stimulus for the repair of long-distance peripheral nerve injury. The results showed that the anisotropic topological scaffolds and non-invasive wireless magnetic stimulation under exogenous SMF could synergistically regulate the morphological change, proliferation and oriented growth of Schwann cells. In vivo experiments confirmed that magnetic CS@AS nerve conduit could better promote the functional recovery and reconstruction of the long-distance injured sciatic nerve under SMF, close to that of the autograft transplantation. Further on, the scaffolds were found to activate the magnetic induction receptors, promote the gene expression related to proliferation, migration and myelin formation, regulate the homeostasis of intracellular Ca2+ and enhance the signal transduction via cGMP-PKG, VEGF, MAPK, and TNF signaling pathways. Therefore, the combination of anisotropic topological nerve grafts and non-invasive wireless magnetic stimulation under external SMF can promote the repair and functional recovery of long-distance nerve injury, providing a new strategy for the treatment of peripheral nerve injury.

Regulating Schwann Cell Growth by Nanosecond Pulsed Electric Field for Peripheral Nerve Regeneration In Vitro.

Schwann cells (SCs) are myelinating cells of the peripheral nervous system, playing a crucial role in peripheral nerve regeneration. Nanosecond Pulse Electric Field (nsPEF) is an emerging method applicable in nerve electrical stimulation that has been demonstrated to be effective in stimulating cell proliferation and other biological processes. Aiming to assess whether SCs undergo significant changes under nsPEF and help explore the potential for new peripheral nerve regeneration methods, cultured RSC96 cells were subjected to nsPEF stimulation at 5 kV and 10 kV, followed by continued cultivation for 3-4 days. Subsequently, some relevant factors expressed by SCs were assessed to demonstrate the successful stimulation, including the specific marker protein, neurotrophic factor, transcription factor, and myelination regulator. The representative results showed that nsPEF significantly enhanced the proliferation and migration of SCs and the ability to synthesize relevant factors that contribute positively to the regeneration of peripheral nerves. Simultaneously, lower expression of GFAP indicated the benign prognosis of peripheral nerve injuries. All these outcomes show that nsPEF has great potential as an efficient treatment method for peripheral nerve injuries by stimulating SCs.

Oriented artificial nanofibers and laser induced periodic surface structures as substrates for Schwann cells alignment

People with injuries to the peripheral nervous system, due to its poor functional regeneration, suffer from paralysis of the facial muscles, fingers and hands, or toes and feet, often for the rest of their lives. Therefore, to improve patients’ quality of life, there is an urgent need for conduits that effectively support the healing of large defects in nerve pathways through specific guidance of nerve cells. This paper describes two specific methods for achieving directed growth of Schwann cells, a type of glial cells that can support the regeneration of the nerve pathway by guiding the neuronal axons in the direction of their alignment. One method implies the exposure of a poly(ethylene terephthalate) (PET) foil to a KrF* laser beam, that renders a nanorippled surface topography. The other method uses aligned polyamide-6 (PA-6) nanofibers produced via electrospinning on a very fast rotating structured collector, which enables easy nanofiber detachment, without additional effort. Schwann cells growth on these substrates was inspected after one week of cultivation by means of scanning electron microscope (SEM). For both methods we show that Schwann cells grow in a certain direction, predetermined by nanoripples and nanofibers orientation. In contrast, cells cultivated onto unstructured surfaces or randomly oriented nanofibers, show an omnidirectional growth behavior.

Nanographene-Au fine-tuning to intensify plasmonic-resonance of polymeric hybrid bionanosystem for synergistic phototherapy and nerve photobiomodulation

Here, we report the multi-photo-bioactivity of the plasmonic-nano graphitic coordinated polycaprolactone-based aligned nanofibrous scaffolds-based bionanosystem for photothermal breast and colon cancer therapies and peripheral nerve photobiomodulation. The size-optimized colloidal reduced graphene oxide (nRGO, 180 nm) nanosheets, for enhanced photothermal impact, were surface-functionalized with gold nanospheres (AuNPs) to prepare the nRGO@AuNP monodispersed nano-composite and then doped 2.0 mg of nRGO@AuNP in biocompatible and biodegradable polymer polycaprolactone (PCL) to fabricate the nRGO@AuNP-PCL (2.0 mg) plasmonic aligned nanofibrous scaffolds. More than 90% of cancer cells, breast cancer (MCF-7) as well as colon cancer (CT-26), ablated after 5 min of low NIR (808 nm) laser power (0.72 W/cm2) illumination with nRGO@AuNP-PCL (2.0 mg) aligned nanofibrous scaffolds. Besides, the nRGO@AuNP-PCL (2.0 mg) provided an extraordinary microenvironment for adhesion, nerve growth, proliferation, and differentiation of PC12 and S42 cells which mimics the natural extracellular matrix. The 2.5-fold increase in neurite length was observed with NIR illumination after 3 days whereas 1.7-fold was found without NIR illumination after 7 days in comparison to PCL (pure). The current findings will be useful to provide a new crucial approach for preparing biocompatible multifunctional composite plasmonic nanofibers as a highly efficient distinct platform for photothermal therapies and promising bioimplants to overcome the loss of sensation after cancer surgery through nerve photobiomodulation.

Multi-needle blow-spinning technique for fabricating collagen nanofibrous nerve guidance conduit with scalable productivity and high performance

Nerve guidance conduits (NGCs) have been widely accepted as a promising strategy for peripheral nerve regeneration. Fabricating ideal NGCs with good biocompatibility, biodegradability, permeability, appropriate mechanical properties (space maintenance, suturing performance, etc.), and oriented topographic cues is still current research focus. From the perspective of translation, the technique stability and scalability are also an important consideration for industrial production. Recently, blow-spinning technique shows great potentials in nanofibrous scaffolds fabrication, possessing high quality, high fiber production rates, low cost, ease of maintenance, and high reliability. In this study, we proposed for the first time the preparation of a novel NGC via blow-spinning technique to obtain optimized performances and high productivity. A new collagen nanofibrous neuro-tube with the bilayered design was developed, incorporating inner oriented and outer random topographical cues. The bilayer structure enhances the mechanical properties of the conduit in dry and wet, displaying good radial support and suturing performance. The porous nature of the blow-spun collagen membrane enables good nutrient delivery and metabolism. The in vitro and in vivo evaluations indicated the bilayer-structure conduit could promoted Schwann cells growth, neurotrophic factors secretion, and axonal regeneration and motor functional recovery in rat.

Progress in methods for evaluating Schwann cell myelination and axonal growth in peripheral nerve regeneration via scaffolds.

Peripheral nerve injury (PNI) is a neurological disorder caused by trauma that is frequently induced by accidents, war, and surgical complications, which is of global significance. The severity of the injury determines the potential for lifelong disability in patients. Artificial nerve scaffolds have been investigated as a powerful tool for promoting optimal regeneration of nerve defects. Over the past few decades, bionic scaffolds have been successfully developed to provide guidance and biological cues to facilitate Schwann cell myelination and orientated axonal growth. Numerous assessment techniques have been employed to investigate the therapeutic efficacy of nerve scaffolds in promoting the growth of Schwann cells and axons upon the bioactivities of distinct scaffolds, which have encouraged a greater understanding of the biological mechanisms involved in peripheral nerve development and regeneration. However, it is still difficult to compare the results from different labs due to the diversity of protocols and the availability of innovative technologies when evaluating the effectiveness of novel artificial scaffolds. Meanwhile, due to the complicated process of peripheral nerve regeneration, several evaluation methods are usually combined in studies on peripheral nerve repair. Herein, we have provided an overview of the evaluation methods used to study the outcomes of scaffold-based therapies for PNI in experimental animal models and especially focus on Schwann cell functions and axonal growth within the regenerated nerve.

Identification of potential common genetic modifiers ofneurofibromas: a genome-wide association study in1333 patients with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is characterized by the highly variable and unpredictable development of benign peripheral nerve sheath tumours: cutaneous (cNFs), subcutaneous (scNFs) and plexiform (pNFs) neurofibromas. To identify neurofibroma modifier genes, in order to develop a database of patients with NF1. All patients were phenotypically evaluated by a medical practitioner using a standardized questionnaire and the causal NF1 variant identified. We enrolled 1333 patients with NF1 who were genotyped for > 7 million common variants. A genome-wide association case-only study identified a significant association with 9q21.33 in the pNF phenotype in the discovery cohort. Twelve, three and four regions suggestive of association at the P ≤ 1 × 10-6 threshold were identified for pNFs, cNFs and scNFs, respectively. Evidence of replication was observed for 4, 2 and 6 loci, including 168 candidate modifier protein-coding genes. Among the candidate modifier genes, some were implicated in the RAS-mitogen-activated protein kinase pathway, cell-cycle control and myelination. Using an original CRISPR/Cas9-based functional assay, we confirmed GAS1 and SPRED2 as pNF and scNF candidate modifiers, as their inactivation specifically affected NF1-mutant Schwann cell growth. Our study may shed new light on the pathogenesis of NF1-associated neurofibromas and will, hopefully, contribute to the development of personalized care for patients with this deleterious and life-threatening condition.

Cervical intradural traumatic neuroma without history of trauma: illustrative case.

Traumatic neuroma typically refers to a reactive process in the injured peripheral nerve, characterized by an excessive growth of axons, Schwann cells, and fibroblasts at the proximal end of the nerve after its interruption. The authors report a case of a traumatic neuroma in the cervical nerve root in a patient with no history of trauma. The patient presented with sensation loss in the right-hand ulnar distribution, right flank around the T4-11 region, and right small toe along with motor power weakness over the right upper and lower extremity. Magnetic resonance imaging revealed an intradural extramedullary mass lesion with extension along the C7 nerve root. Histological examination showed traumatic neuroma. A total resection of the lesion along with the resolution of sensory and motor deficits was achieved directly after surgery. Traumatic neuroma should always be kept in the armamentarium for diagnosis of an intradural nerve sheath tumor.

Schwann Cells Reprogram Into Repair Phenotype Instead of Dedifferentiating to Immature Phenotype in in Vitro Culture

Introduction: In vitro cultured Schwann cell has been suggested to adopt a phenotype of undifferentiated immature Schwann cells found in vivo during development. However, recent studies indicate that Schwann cells undergo cellular reprogramming into the phenotype of repair Schwann cells instead of reverting to an immature phenotype after peripheral nerve injury. The study hypothesized that in in vitro culture, Schwann cells assume the repair phenotype instead of de-differentiating to immature Schwann cells, similar to in vivo nerve injury response. Therefore, this study aimed to characterize the phenotype of cultured Schwann cells by examining the expression of classic Schwann markers and transcription factors c-Jun and Krox-20. Methods: Schwann cells, isolated from Wistar rat sciatic nerve, were grown in a standard Schwann cell growth medium for seven days. Then, cultured Schwann cells were analyzed using immunofluorescence analysis for classic Schwann cell markers (neurotrophin receptor p75 (p75NTR) and myelin basic protein (MBP)) and the expression profile of transcription factor c-Jun and Krox-20. Results: Immunofluorescence analysis revealed that cultured Schwann cells expressed a significantly high level of repair phenotype biomarkers (p75NTR and c-Jun) compared to the level of myelinating phenotype biomarkers (MBP and Krox-20). Conclusion: Schwann cells reprogram into repair Schwann cells instead of de-differentiating to immature Schwann cells in vitro.

Wet spinning is employed to produce spider silk with high elasticity

Spider silk exhibits exceptional strength and elasticity in its natural form. Over the course of several decades, researchers have been working on artificially spinning recombinant spider silk proteins (spidroin) in order to replicate the remarkable mechanical properties of natural spider silk. In this study, we utilized the wet spinning method to investigate the relationship between the concentration of the coagulation bath and fiber performance. We discovered that the concentration of methanol plays a crucial role in determining the continuity, diameter, and mechanical properties of the fibers. Lower concentrations of methanol favor the production of continuous, thinner fibers with higher strain. Additionally, secondary stretching during the spinning process contributes to the production of silk fibers with stable mechanical properties and thermal stability. By employing different concentrations of methanol and applying additional stretching, we successfully produced silk fibers with a high strain of 2.1652 ± 0.3871 mm/mm. Furthermore, these wet-spun fibers demonstrated the ability to promote the growth of Schwann cells, indicating their potential application in the field of biomedical engineering. Hence, the exceptional mechanical properties and the ability to promote cellular growth make the obtained spider silk fibers highly promising for various biomedical applications.

Electrospun Piezoelectric Scaffold with External Mechanical Stimulation for Promoting Regeneration of Peripheral Nerve Injury.

Safe and efficient provision of electrical stimulation (ES) for nerve repair and regeneration is a problem that needs to be addressed. In this study, a silk fibroin/poly(vinylidene fluoride-co-hexafluoropropylene)/Ti3C2Tx (SF/PVDF-HFP/MXene) composite scaffold with piezoelectricity was developed by electrospinning technology. MXene was loaded to the scaffold to enhance the piezoelectric properties (Output voltage reaches up to 100 mV), mechanical properties, and antibacterial activity. Cell experiments demonstrated piezoelectric stimulation under external ultrasonication for promoting the growth and proliferation of Schwann cells (SCs) cultured on this electrospun scaffold. Further in vivo study with rat sciatic nerve injury model revealed that the SF/PVDF-HFP/MXene nerve conduit could induce the proliferation of SCs, enhance the elongation of axon, and promote axonal myelination. Under the piezoelectric effect of this nerve scaffold, the rats with regenerative nerve exhibited a favorable recovery effect of motor and sensory function, indicating a safe and feasible method of using this SF/PVDF-HFP/MXene piezoelectric scaffold for ES provision in vivo.

Micron track chitosan conduit fabricated by 3D-printed model topography provides bionic microenvironment for peripheral nerve regeneration.

The micron track conduit (MTC) and nerve factor provide a physical and biological model for simulating peripheral nerve growth and have potential applications for nerve injury. However, it has rarely been reported that they synergize on peripheral nerves. In this study, we used bioderived chitosan as a substrate to design and construct a neural repair conduit with micron track topography using threedimensional (3D) printing topography. We loaded the MTC with neurotrophin-3 (NT-3) to promote the regeneration of sensory and sympathetic neurons in the peripheral nervous system. We found that the MTC@NT3 composite nerve conduit mimicked the microenvironment of peripheral nerves and promoted axonal regeneration while inducing the targeted growth of Schwann cells, which would promote functional recovery in rats with peripheral nerve injury. Artificial nerve implants with functional properties can be developed using the strategy presented in this study.

Role of transforming growth factor-β in peripheral nerve regeneration.

Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits. Unlike in the central nervous system, damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells. However, axon regeneration and repair do not automatically result in the restoration of function, which is the ultimate therapeutic goal but also a major clinical challenge. Transforming growth factor (TGF) is a multifunctional cytokine that regulates various biological processes including tissue repair, embryo development, and cell growth and differentiation. There is accumulating evidence that TGF-β family proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells; recruiting specific immune cells; controlling the permeability of the blood-nerve barrier, thereby stimulating axon growth; and inhibiting remyelination of regenerated axons. TGF-β has been applied to the treatment of peripheral nerve injury in animal models. In this context, we review the functions of TGF-β in peripheral nerve regeneration and potential clinical applications.

Bioengineering approaches for nerve graft revascularization: Current concepts and future directions.

Peripheral nerve injury (PNI) is the most common neurological injury in civilian and military injuries, with over 360,000 PNI procedures performed in the US yearly. Segmental loss of nerve tissue results in a nerve gap precluding a tension-free primary repair, and in these cases, interpositional autologous or acellular nerve allografts are used to bridge the gap. Graft ischemia time is a critical factor in achieving satisfactory nerve regeneration. Rapid nerve graft revascularization is essential in order to sustain Schwann cell growth which in turn is crucial for axonal regeneration. Currently, nerve autografts are considered the gold standard for segmental nerve gaps but are associated with several disadvantages such as limited supply of expendable donor tissue, increased operative time, and donor site morbidity. Hence, readily available, off-the-shelf nerve allografts or scaffolds are being investigated since they provide advantages such as a virtually limitless sourcing, a wide variety of sizes to match recipient nerves, and no donor site morbidity. New, exciting advances in tissue engineering to augment revascularization of nerve allografts or conduits have been investigated. Strategies include pro-angiogenic mesenchymal stem cells, extracellular vesicles, functionalized scaffolds, bioactive peptides, and three-dimensional bioprinting. This article discusses these bioengineering advances and future strategies aimed at enhancing nerve graft and scaffold revascularization. This article is categorized under: Neurological Diseases > Biomedical Engineering Neurological Diseases > Molecular and Cellular Physiology.

3D Printed Conductive Multiscale Nerve Guidance Conduit with Hierarchical Fibers for Peripheral Nerve Regeneration.

Nerve guidance conduits (NGCs) have become a promising alternative for peripheral nerve regeneration; however, the outcome of nerve regeneration and functional recovery is greatly affected by the physical, chemical, and electrical properties of NGCs. In this study, a conductive multiscale filled NGC (MF-NGC) consisting of electrospun poly(lactide-co-caprolactone) (PCL)/collagen nanofibers as the sheath, reduced graphene oxide /PCL microfibers as the backbone, and PCL microfibers as the internal structure for peripheral nerve regeneration is developed. The printed MF-NGCs presented good permeability, mechanical stability, and electrical conductivity, which further promoted the elongation and growth of Schwann cells and neurite outgrowth of PC12 neuronal cells. Animal studies using a rat sciatic nerve injury model reveal that the MF-NGCs promote neovascularization and M2 transition through the rapid recruitment of vascular cells and macrophages. Histological and functional assessments of the regenerated nerves confirm that the conductive MF-NGCs significantly enhance peripheral nerve regeneration, as indicated by improved axon myelination, muscle weight increase, and sciatic nerve function index. This study demonstrates the feasibility of using 3D-printed conductive MF-NGCs with hierarchically oriented fibers as functional conduits that can significantly enhance peripheral nerve regeneration.

Gastric schwannoma diagnosing gastric stromal tumor.

A 45-year-old male visited our hospital for a medical examination without any clinical complaints. The patient had an gastroscopy, which revealed a 30mm*30mm hemispherical submucosal tumor arising from the lesser curvature of the gastric body , suggesting a gastrointestinal stromal tumor (GIST) as a preoperative diagnosis;Endoscopic resection was determined to be the best choice and the patient underwent a endoscopic full-thickness resection and endoscopic purse-string suture. Except for a slight low fever, the patient was well recovered and was discharged on his 7th post-operation. Pathological analysis and immunohistochemical staining showed fascicular growth of neoplastic Schwann cells and confirmed the diagnosis of gastric schwannoma through high positivity for S-100 protein.

Artificial nerve graft constructed by coculture of activated Schwann cells and human hair keratin for repair of peripheral nerve defects.

Studies have shown that human hair keratin (HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secrete nerve growth factor, which promotes neural regeneration. Therefore, HHK with Schwann cells may be a more effective approach to repair nerve defects than HHK without Schwann cells. In this study, we established an artificial nerve graft by loading an HHK skeleton with activated Schwann cells. We found that the longitudinal HHK microfilament structure provided adhesion medium, space and direction for Schwann cells, and promoted Schwann cell growth and nerve fiber regeneration. In addition, interleukin-1β not only activates Schwann cells, but also strengthens their activity and increases the expression of nerve growth factors. Activated Schwann cells activate macrophages, and activated macrophages secrete interleukin-1β, which maintains the activity of Schwann cells. Thus, a beneficial cycle forms and promotes nerve repair. Furthermore, our studies have found that the newly constructed artificial nerve graft promotes the improvements in nerve conduction function and motor function in rats with sciatic nerve injury, and increases the expression of nerve injury repair factors fibroblast growth factor 2 and human transforming growth factor B receptor 2. These findings suggest that this artificial nerve graft effectively repairs peripheral nerve injury.