Regeneration Of Peripheral Nerve Injury Research Articles

4D-Printed MXene-Based Artificial Nerve Guidance Conduit for Enhanced Regeneration of Peripheral Nerve Injuries.

Repairing larger defects (> 5mm) in peripheral nerve injuries (PNIs) remains a significant challenge when using traditional artificial nerve guidance conduits (NGCs). We propose a novel approach that combines 4D printing technology with poly(L-lactide-co-trimethylene carbonate) (PLATMC) and Ti3C2Tx MXene nanosheets, thereby imparting shape memory properties to the NGCs. Upon body temperature activation, the printed sheet-like structure can quickly self-roll into a conduit-like structure, enabling optimal wrapping around nerve stumps. This design enhances nerve fixation and simplifies surgical procedures. Moreover, the integration of microchannel expertly crafted through 4D printing, along with the incorporation of MXene nanosheets, introduces electrical conductivity. This feature facilitates the guided and directional migration of nerve cells, rapidly accelerating the healing of the PNI. By leveraging these advanced technologies, the developed NGCs demonstrate remarkable potential in promoting peripheral nerve regeneration, leading to substantial improvements in muscle morphology and restored sciatic nerve function, comparable to outcomes achieved through autogenous nerve transplantation. This article is protected by copyright. All rights reserved.

Biomimetic-inspired piezoelectric ovalbumin/BaTiO3 scaffolds synergizing with anisotropic topology for modulating Schwann cell and DRG behavior

The treatment of peripheral nerve injury is a clinical challenge that tremendously affected the patients' health and life. Anisotropic topographies and electric cues can simulate the regenerative microenvironment of nerve from physical and biological aspects, which show promising application in nerve regeneration. However, most studies just unilaterally emphasize the effect of sole topological- or electric- cue on nerve regeneration, while rarely considering the synergistic function of both cues simultaneously. In this study, a biomimetic-inspired piezoelectric topological ovalbumin/BaTiO3 scaffold that can provide non-invasive electrical stimulation in situ was constructed by combining piezoelectric BaTiO3 nanoparticles and surface microtopography. The results showed that the incorporation of piezoelectric nanoparticles could improve the mechanical properties of the scaffolds, and the piezoelectric output of the scaffolds after polarization was significantly increased. Biological evaluation revealed that the piezoelectric topological scaffolds could regulate the orientation growth of SCs, promote axon elongation of DRG, and upregulate the genes expression referring to myelination and axon growth, thus rapidly integrated chemical-mechanical signals and transmitted them for effectively promoting neuronal myelination, which was closely related to peripheral neurogenesis. The study suggests that the anisotropic surface topology combined with non-invasive electronic stimulation of the ovalbumin/BaTiO3 scaffolds possess a promising application prospect in the repair and regeneration of peripheral nerve injury.

Fas ligand regulate nerve injury and repair by affecting AKT, β-catenin, and NF-κB pathways

ObjectiveTo investigate the regulatory effect of Fas-L on the repair and regeneration of peripheral extension injury in rats. MethodsThis study aimed to explore the effects of Fas-L on apoptosis and axonal regeneration of dorsal root ganglion (DRG) cells in rat peripheral nerve repair and regeneration by using several relevant experimental techniques from the injured nerve animal model, cell biology, and molecular biology. ResultsThe expression level of Fas-L in DRG tissues was significantly down-regulated after sciatic nerve injury. Interference with Fas-L can significantly promote the regeneration of DRG neuronal axons and inhibit apoptosis, while the overexpression of Fas-L is contrary to it. Moreover, Fas-L may play a role in the regulation of DRG function and the repair and regeneration of peripheral nerves in Sprague Dawley (SD) rats by affecting several signaling pathways, such as p-AKT/AKT, β-catenin, and NF-κB. ConclusionFas-L may have a certain effect on the repair and regeneration of peripheral nerve injury in SD rats, which may provide an experimental basis and a new theoretical basis for the functional reconstruction of peripheral nerves. Significance statementThe expression level of Fas-L in DRG tissues was significantly down-regulated after sciatic nerve injury. Fas-L can significantly promote the regeneration of DRG neuronal axons and inhibit apoptosis. Fas-L may play a role in the regulation of DRG function and the repair and regeneration of peripheral nerves in SD rats by affecting several signaling pathways, such as p-AKT/AKT, β-catenin, and NF-κB. Fas-L may have a certain effect on the repair and regeneration of peripheral nerve injury in SD rats, which may provide an experimental basis and a new theoretical basis for the functional reconstruction of peripheral nerves.

Platelet Lysate Promotes Proliferation and Angiogenic Activity of Dental Pulp Stem Cells via Store-operated Ca2+ Entry

AimsDental pulp stem cells (DPSCs) had been widely used in nerve tissue engineering. However, the low cell survival and invalid differentiation were urgent problems to be solved for cell-based therapy. Platelet lysate (PL) had attracted attentions for its good biocompatibility, low side effects and abundant growth factors. In this study, we aimed to evaluate the effect and mechanism of PL on the proliferation and angiogenesis of DPSCs. Materials and methodsIn our study, PL was prepared by repeated freeze-thaw methods. The effect of PL on the viability of DPSCs was screened by the Cell Counting Kit-8 (CCK-8) and Live/Dead assays. Then the store-operated Ca2+ entry (SOCE) agonist endothelin-1 (ET-1) and inhibitor 2-aminoethoxydiphenyl borate (2-APB) were used to clarify the biological functions of PL on DPSCs. We detected the mitosis of DPSCs by KI67 immunofluorescence staining. Moreover, Ca2+ influx in DPSCs was evaluated by fluorescence microscopy and a flow cytometry. The expression of p-SRC, VEGFA and CD31 as well as the number of formed tubules in each group were investigated, so as to further reveal the influence of PL on the DPSCs angiogenic activity. ResultsAs for CCK-8 and Live/Dead assays, the results indicated the 0.5% concentration of PL was better than that of 20ng/ml bFGF and 10% FBS in promoting cell survival within 24hours. KI67 staining showed that 0.5% PL promoted SOCE and cell proliferation. The expression levels of SRC phosphorylation (p-SRC) were increased in the 0.5% PL and ET-1 + 0.5% PL groups, as well as the expressions of endothelial markers CD31 and VEGFA were also increased in the ET-1, 0.5% PL and ET-1 + 0.5% PL groups. However, CD31 and VEGFA were not detected in 2-APB and 2-APB + 0.5% PL groups. After angiogenesis induction, capillary-like structures were observed in ET-1, 0.5% PL and ET-1 + 0.5% PL groups, whereas no vascular structures were observed in 2-APB and 2-APB + 0.5% PL groups. ConclusionOur results indicated that PL promoted the proliferation and vessel-formation of DPSCs via the activation of SOCE and the upregulation of p-SRC and VEGFA expressions, respectively. PL might act as a promising cell supplement in DPSCs survival and differentiation, furtherly applied for the repair and regeneration of peripheral nerve injury.

Effective regeneration of rat sciatic nerve using nanofibrous scaffolds containing rat ADSCs with controlled release of rhNGF and melatonin molecules for the treatment of peripheral injury model

Different therapeutic strategies have been designed and developed for the repair and regeneration of peripheral nerve injury (PNI) tissue as a result of advancements in tissue engineering and regenerative medicine. Due to its versatility, controlled delivery and administration of multifunctional therapeutic agents can be regarded of as an effective strategy in treating nerve injury. In this study, melatonin (Mel) molecules and recombinant human nerve growth factor (rhNGF) were loaded on the surface and in the core of polycaprolactone/chitosan (PCL/CS) blended nanofibrous scaffold. To simulate the in vivo microenvironment, a dual-delivery three-dimensional (3-D) nanofibrous matrix was developed and the in vitro neural development of stem cell differentiation process was systematically examined. The microscopic technique with acridine orange and ethidium bromide (AO/EB) fluorescence staining method was used to establish the adipose-derived stem cells (ADSCs) differentiation and cell–cell communications, which demonstrated that the effective differentiation of the ADSCs with nanofibrous matrix. As investigated observations, ADSCs differentiation was further evident through cell migration assay and gene expression analysis. According to the biocompatibility analysis, the nanofibrous matrix did not trigger any adverse immunological reactions. Based on these characteristics, a 5-week in vivo investigation examined the potential of the developed nanofibrous matrix in the regeneration of sciatic nerve of rats. Additionally, compared to the negative control group, the electrophysiological and walking track analyses demonstrated improved sciatic nerve regeneration. This study demonstrates the nanofibrous matrix's ability to regenerate peripheral nerves.

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.

Repair and regeneration of peripheral nerve injuries that ablate branch points.

The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS have been extensively studied and routinely treated with autografts, acellular nerve allografts, conduits, wraps, and nerve transfers. In contrast, segmental-loss peripheral nerve injuries, in which one or more branch points are ablated so that there are three or more nerve endings, present additional complications that have not been rigorously studied or documented. This review discusses: (1) the branched anatomy of the peripheral nervous system, (2) case reports describing how peripheral nerve injuries with branched ablations have been surgically managed, (3) factors known to influence regeneration through branched nerve structures, (4) techniques and models of branched peripheral nerve injuries in animal models, and (5) conclusions regarding outcome measures and studies needed to improve understanding of regeneration through ablated branched structures of the peripheral nervous system.

Human Olfactory Ecto-mesenchymal Stem Cells Displaying Schwann-cell-like Phenotypes and Promoting Neurite Outgrowth in Vitro.

Strategies of Schwann cell (SC) transplantation for regeneration of peripheral nerve injury involve many limitations. Stem cells can be used as alternative cell source for differentiation into Schwann cells. Given the high potential of neural crest-derived stem cells for the generation of multiple cell lineages, in this research, we considered whether olfactory ectomesenchymal stem cells (OE-MSCs) derived from neural crest can spontaneously differentiate into SC lineage. OE-MSCs were isolated from human nasal mucosa and characterized by the mesenchymal and neural crest markers. The cells were cultured in glial growth factors-free medium and further investigated in terms of the phenotypic and functional properties. Immunocytochemical staining and real-time PCR analysis indicated that the cultured OE-MSCs expressed SCs markers, SOX10, p75, S100, GFAP and MBP, differentiation indicative. It was found that the cells could secrete neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Furthermore, after co-cultured with PC12, the mean neurite length was enhanced by OE-MSCs. The findings indicated that OE-MSCs could be differentiated spontaneously into SC-like phenotypes, suggesting their applications for transplantation in peripheral nerve injuries.

Parthenolide promotes expansion of Nestin+ progenitor cells via Shh modulation and contributes to post-injury cerebellar replenishment.

Background: Regeneration of injuries occurring in the central nervous system is extremely difficult. Studies have shown that the developing cerebellum can be repopulated by a group of Nestin-expressing progenitors (NEPs) after irradiation injury, suggesting that modulating the mobilization of NEPs is beneficial to promoting nerve regeneration. To date, however, effect of exogenous pharmaceutical agonist on NEPs mobilization remains unknown. Parthenolide (PTL), a sesquiterpene lactone isolated from shoots of feverfew. Although it has been shown to possess several pharmacological activities and is considered to have potential therapeutic effects on the regeneration of peripheral nerve injury, its efficacy in promoting central nervous system (CNS) regeneration is unclear. In this study, we aimed to elucidate the role and possible mechanism of PTL on regeneration in injured CNS after irradiation using a developing cerebellum model. Methods: We investigated the radioprotective effects of PTL on the developing cerebellum by immunoblotting as well as immunofluorescence staining and ROS detection in vivo and in vitro experiments, and then determined the effects of PTL on NEPs in Nestin CFP and Nestin GFP fluorescent mice. Inducible lineage tracing analysis was used in Nestin-CreERT2×ROSA26-LSL YFP mice to label and track the fate of NEPs in the cerebellum after irradiation. Combined with cell biology and molecular biology techniques to determine changes in various cellular components in the cerebellum and possible mechanisms of PTL on NEPs mobilization in the injured developing cerebellum. Results: We found that PTL could attenuate radiation-induced acute injury of granule neuron progenitors (GNPs) in irradiated cerebellar external granule layer (EGL) by alleviating apoptosis through regulation of the cells' redox state. Moreover, PTL increased cerebellar Shh production and secretion by inhibiting the PI3K/AKT pathway, thus promoting expansion of NEPs, which is the compensatory replenishment of granule neurons after radiation damage. Conclusion: Collectively, our results indicate that activation and expansion of NEPs are critical for regeneration of the injured cerebellum, and that PTL is a promising drug candidate to influence this process.

Multifunctional biomimetic hydrogel based on graphene nanoparticles and sodium alginate for peripheral nerve injury therapy.

Peripheral nerve injury (PNI) caused by injury may influence the patients' lifelong mobility unless there is an appropriate treatment. Tissue engineering has become a hot field to replace traditional autologous nerve transplantation due to its low surgical damage and easy-to-industrial advantages. Graphene (GR) is a kind of carbon nanomaterial with good electrical and mechanical properties that satisfy the demand for a good tissue scaffold for nerve regeneration. Herein, a novel and biosafe hydrogel is fabricated by using graphene and sodium alginate (GR-SA) together. This hydrogel not only can mimic the nerve growth microenvironment but also can promote the expression of neurotrophic substances and growth factors. Additionally, GR-SA hydrogel can significantly reduce inflammatory factors. Moreover, the results of both in vitro and in vivo tests demonstrate that GR-SA hydrogel has a promising prospect in PNI regeneration.

The Role of NGF in the Regeneration of Peripheral Nerve Injury – Systematic Review – Implications for the Provision of Days of Medical Care after Peripheral Nerve Injuries

The Role of NGF in the Regeneration of Peripheral Nerve Injury – Systematic Review – Implications for the Provision of Days of Medical Care after Peripheral Nerve Injuries

Exosomes produced by adipose-derived stem cells inhibit schwann cells autophagy and promote the regeneration of the myelin sheath.

Peripheral nerve injury (PNI) is encountered relatively commonly in the clinic and often results in long-term functional deficits. Research to develop methods to improve regeneration following nerve injury is ongoing. Numerous studies have shown that adipose-derived stem cells (ADSCs) promote the regeneration of peripheral nerve injury; however, the mechanism is unclear. Autophagy, a highly conserved intracellular process responsible for maintaining cellular homeostasis, and Schwann cells (SCs), play important roles in regeneration after PNI. In the present study, we explored the effect and mechanism of exosomes produced by adipose-derived stem cells (ADSC-Exos) on autophagy of SCs in PNI, as well as their effect on the regeneration of the nerve myelin sheath. The levels of autophagy and the expression of karyopherin subunit alpha 2 (Kpna2) in SCs increased markedly after the sciatic nerve was injured in SCs (SNI-SCs). The enhanced autophagy and the upregulated Kpna2 in SNI-SCs were inhibited after treatment with ADSC-Exos in vivo and in vitro. The effect of ADSC-Exos on inhibiting SC autophagy was blocked by overexpression of Kpna2 in SNI-SCs. Using quantitative real-time reverse transcription PCR, ADSC-Exos were demonstrated to contain a large amount of miRNA-26b, which was predicted to regulate Kpna2 on the TargetScan website. The effect of ADSC-Exos on inhibiting SCs autophagy was blocked after the silencing of miRNA-26b. Moreover, ADSC-Exos promoted the regeneration of the myelin sheath by inhibiting SC autophagy in rat SNI models. In conclusion, our results indicated that ADSC-Exos promote the regeneration of the myelin sheath by moderately reducing autophagy of injured SCs via miRNA-26b downregulation of Kpna2.

Efficacy of multi-wave locked system laser therapy on nerve regeneration after crushing in Wister rats.

[Purpose] To investigate the efficacy of the multi-wave locked system laser therapy on the regeneration of peripheral nerve injuries by evaluating the functional, electrophysiological, and morphological changes of the crushed sciatic nerve in Wistar rats. [Materials and Methods] Sixty male Wistar rats (200–250 g) were randomly assigned to control negative, control positive, or laser groups and subjected to no laser therapy or crushing, to crushing without laser therapy, or crushing followed by multi-wave locked system laser therapy five times/week for four weeks (power=1 W, energy density=10 J/cm2, total energy=100 J), respectively. Functional, electrophysiological, and morphometric analyses were performed before and 7, 15, 21, and 28 days after crushing. The sciatic functional index, compound motor action potential amplitude, motor nerve conduction velocity, and nerve and myelin sheath diameters were measured. [Results] The sciatic functional index value decreased significantly, while the compound motor action potential amplitude, motor nerve conduction velocity, nerve diameter, and myelin sheath diameter increased significantly in the laser group post-treatment compared to the values in the control groups. [Conclusion] Multi-wave locked system laser therapy was effective in accelerating the regeneration of crushed sciatic nerves in Wistar rats.

High molecular weight form of hyaluronic acid reduces neuroinflammatory response in injured sciatic nerve via the intracellular domain of CD44.

Inflammatory response after peripheral nerve injury is required for clearance of tissue debris and effective regeneration. Studies have revealed that hyaluronic acid (HA) may exert different properties depending on their molecular size. High molecular weight HA (>>1,000 kDa; HMW-HA) displays immunosuppressive properties, whereas low molecular weight HA (<800 kDa; LMW-HA) induces proinflammatory responses. The role of HMW-HA interaction with CD44, a major HA receptor, in neuroinflammatory responses has not been fully elucidated. The purpose of this experimental study was to investigate the effects of topical applications of HMW-HA on the sciatic nerve injury in an adult rat model. At the crush site on the sciatic nerve, the recordings of compound muscle action potential (CMAP) and the levels of several proteins related to inflammatory response were assessed at time intervals of 2, 4, and 6 weeks postsurgery. Here, we show that the recovery effect of HMW-HA treatment had significantly shortened latency and increased amplitude of CMAP compared with crushed alone, crushed plus γ-secretase inhibitor with or without HA treatment at 6 weeks after surgery. Our data reveal that HMW-HA could downregulate the expression of IL1-β, TLR4, and MMP-9, whereas these proteins expression were increased when the CD44-ICD activity was inhibited using γ-secretase inhibitor. Our findings demonstrated a novel role of CD44-ICD in HA-mediated recovery of peripheral nerve injury. Clinical relevance: an alternative for the regeneration of peripheral nerve injury.

MicroRNA-192-5p is involved in nerve repair in rats with peripheral nerve injury by regulating XIAP

ABSTRACT Objective: MicroRNAs (miRNAs) have been demonstrated to engage in the nerve injury, while the effect of microRNA-192-5p (miR-192-5p) on the nerve repair has not yet been well understood. This study is performed to investigate how miR-192-5p affects nerve repair in rats with peripheral nerve injury by regulating X-linked inhibitor of apoptosis protein (XIAP). Methods: The rat model of left sciatic nerve injury was established, and the expression of miR-192-5p was then detected. A series of experiments were conducted to investigate the role of miR-192-5p on nerve repair in rats with peripheral nerve injury. The expression of apoptosis-related proteins (Caspase-3, Bax and Bcl-2) and nerve repair factors (NGF, BDNF, and GAP-43) was measured. Bioinformatics analysis and dual-luciferase reporter gene assay confirmed the targeting relationship between miR-192-5p and XIAP. Results: MiR-192-5p inhibition promoted the recovery of sensory function and the recovery and regeneration in rats with sciatic nerve injury. MiR-192-5p inhibition promoted the recovery of muscle atrophy caused by nerve injury. MiR-192-5p inhibition inhibited neuronal apoptosis by affecting the expression of apoptosis-related proteins and promoted the recovery of nerve function by elevating the expression of nerve repair factors induced by peripheral nerve injury. Bioinformatics analysis and dual-luciferase reporter gene assay confirmed that XIAP was a target gene of miR-192-5p. Conclusion: This study demonstrates that miR-192-5p inhibition can up-regulate the expression of XIAP, decrease the apoptosis of nerve cells, and promote the repair and regeneration of peripheral nerve injury.

Cell-Enhanced Acellular Nerve Allografts for Peripheral Nerve Reconstruction: A Systematic Review and a Meta-Analysis of the Literature.

Peripheral nerve reconstruction is a difficult problem to solve. Acellular nerve allografts (ANAs) have been widely tested and are a promising alternative to the autologous gold standard. However, current reconstructive methods still yield unpredictable and unsuccessful results. Consequently, numerous studies have been carried out studying alternatives to plain ANAs, but it is not clear if nerve regeneration potential exists between current biological, chemical, and physical enrichment modes. To systematically review the effects of cell-enhanced ANAs on regeneration of peripheral nerve injuries. PubMed, ScienceDirect, Medline, and Scopus databases were searched for related articles published from 2007 to 2017. Inclusion criteria of selected articles consisted of (1) articles written in English; (2) the topic being cell-enhanced ANAs in peripheral nerve regeneration; (3) an in vivo study design; and (4) postgrafting neuroregenerative assessment of results. Exclusion criteria included all articles that (1) discussed central nervous system ANAs; (2) consisted of xenografts as the main topic; and (3) consisted of case series, case reports or reviews. Forty papers were selected, and categorization included the animal model; the enhancing cell types; the decellularization method; and the neuroregenerative test performed. The effects of using diverse cellular enhancements combined with ANAs are discussed and also compared with the other treatments such as autologous nerve graft, and plain ANAs. ANAs cellular enhancement demonstrated positive effects on recovery of nerve function. Future research should include clinical translation, in order to increase the level of evidence available on peripheral nerve reconstruction.

Exosomes Derived from ADSCs Promote the Regeneration of Myelin Sheath by Inhibiting SCs Autophagy via miRNA26b Targeting KPNA2

Background: Peripheral nerve injury is encountered quite commonly in the clinic and often results in long-term functional deficits. Investigation toward the development of methods to improve regeneration following nerve injury is ongoing. Numerous studies proved that adipose-derived stem cells (ADSCs) promote the regeneration of peripheral nerve injury, but the mechanism is not clear. Autophagy, highly conserved intracellular process responsible for maintaining cellular homeostasis, and Schwann cells (SCs) play important roles in the regeneration of peripheral nerve injury. Methods: In this study, we explored the effect of ADSC-derived exosomes (ADSC-Exos) on the SCs autophagy and the regeneration of myelin sheath after sciatic nerve injury. Findings: The enhanced autophagy was inhibited, the up-regulated expression of KPNA2 was decreased, and the down-regulated levels of miRNA-26b was increased in injured SCs after treatment with ADSCs-Exos. Usingreal-time PCR, ADSC-Exos were shown to contained a large number of miRNA-26b. The effect of ADSC-Exos inhibiting SCs autophagy were blocked after the over-expression of KPNA2 or the silence of miRNA-26b. Moreover, ADSC-Exos promoted the regeneration of myelin sheaths of injured sciatic nerves in rats. Interpretation: Our results indicate that ADSC-Exos promote the regeneration of myelin sheath by moderately reducing autophagy of injured SCs via miRNA-26b down-regulating KPNA2. Funding Statement: This study was supported by National Key R&D Program of China (2018YFA0107500), National Natural Science Foundation of China (81572146, 31771511), Shanghai Health System Excellent Discipline Leadership Program(2017BR034)and China Postdoctoral Science Foundation (2017M623362, 2018T111131). Declaration of Interests: The authors report no conflicts of interest in this work. Ethics Approval Statement: All animal experiments met the requirements of the Ethics Committee.

Aligned Chitosan-Gelatin Cryogel-Filled Polyurethane Nerve Guidance Channel for Neural Tissue Engineering: Fabrication, Characterization, and In Vitro Evaluation

Recent trends in peripheral nerve regeneration are directed toward the development of nerve guidance channels to assist the regeneration of the nerves across critical size defects. Advanced nerve guidance channels (aNGCs) should possess multifunctional properties to direct the axonal regeneration from proximal to distal end, allow the concentration of growth factors secreted by the injured nerve end, and attenuate the ingrowth of scar tissue at the site of injury. The design of the nerve guidance channel (NGC) is critical for providing the necessary topographical, chemotactic, as well as haptotactic cues for efficient nerve regeneration. In this study, we have designed and fabricated clinically relevant aNGCs comprising an antioxidant polyurethane (PUAO) conduit filled with aligned chitosan-gelatin (CG) cryogel filler for peripheral nerve regeneration. The effects of temperature, polymer concentration, and cross-linker concentration on the physicochemical properties of the CG cryogel filler were studied. The synthesized scaffolds were evaluated by scanning electron microscopy (SEM) and compression testing to obtain the matrix best suited to form the aNGC. The nanofibrous PUAO conduit was fabricated by electrospinning with a wall thickness of 114.16 ± 26.91 μm, which was filled with CG (1.2/6.4%)-aligned cryogel matrix to obtain the aNGCs. The aNGCs with 2.01 ± 0.04 mm internal diameter, 15 mm length, and internal CG filler with a pore diameter of 29.60 ± 9.83 μm were fabricated. The aNGCs were evaluated by SEM and in vitro neuronal culture for biocompatibility and cellular alignment. In vitro dorsal root ganglion cultures showed the aligned growth and cellular migration along the aligned pores of aNGCs. With this study, we conclude that this clinically relevant aligned porous aNGC will have a promising effect in repair and regeneration of peripheral nerve injuries.

Hydroxyapatite coated magnesium alloy for peripheral nerve regeneration

Magnesium (Mg) has been used as a neuroprotective agent and for orthopedic and cardiovascular stent applications for a long time. Mg is a promising material for neural regeneration own to its metallic nature, biodegradability, and biocompatibility. To evaluate the benefit of hydroxyapatite (HA) coated Mg alloy (WE43) nerve conduit in peripheral nerve injury regeneration. In vitro cell adhesion and proliferation of PC12 cells and Schwann cells over pure Mg, WE43, HA coated pure Mg (HA-Mg), and HA coated WE43 (HA-WE43) disks were assessed using scanning electron microscope and EZ-CYTOX assay. In vivo study was also performed for sham, silicone nerve conduits, and HA-WE43 nerve conduits to evaluate rat sciatic nerve regeneration over 10 mm gap. These rats were observed for three months with weekly functional assessment using sciatic functional index. Regeneration was evaluated through retrograde neuron labeling and histomorphometric analysis at the end of the experiment. Non-coated pure Mg and WE43 conduits showed fast resorption rate and high gas formation. Higher adhesion and proliferation of PC12 cells were found in HA-WE43 disks. At the end of three months, HA-WE43 nerve conduit showed mild resorption without detectable gas formation in the surrounding tissue. However, only scanty regenerated neural tissue was found within the conduit. HA-WE43 nerve conduit showed controlled degradation and absence of gas formation with scanty regenerated neural tissue.

Research progress of sumoylation in the regeneration of peripheral nerve injury

Small ubiquitin-related modifiers (SUMOs) are discovered in recent years as a kind of important protein involved in the post-translational protein modification, and sumoylation plays an important role in a variety of biological processes in the human body. Peripheral nerve injuries are common in clinic, and the regeneration after injury is a rather complicated process. This article will review the latest research on the role of SUMO modification in the regeneration of peripheral nerve injury. Key words: Small ubiquitin-related modifier; Peripheral nerve injury; Neural repair and regeneration