Traumatic peripheral nerve injuries are a major contributor to long-term disability,accounting for nearly half of all peripheral nervous system disorders.Although autologous nerve grafting remains the clinical gold st...Traumatic peripheral nerve injuries are a major contributor to long-term disability,accounting for nearly half of all peripheral nervous system disorders.Although autologous nerve grafting remains the clinical gold standard,it is limited by donor-site morbidity and often fails to achieve full functional recovery.Biodegradable collagen conduits have emerged as an appealing alternative,providing a scaffold for directed axonal growth without requiring graft harvest.We reported three cases of chronic nerve injuries(6-12 months post-trauma):two involving 2.0-3.5 cm ulnar nerve defects in the forearm and one with a 2.5 cm median nerve defect at the wrist.Under microscopic guidance,each defect was bridged with a tubular type I collagen conduit secured by epineurial sutures,followed by standardized physiotherapy and sensory reeducation.At 12-18 months of follow-up,all patients demonstrated near-complete sensory recovery—two-point discrimination and Semmes-Weinstein thresholds returned to≤6 mm—and motor function improved to Medical Research Council grades 4-5,restoring fine dexterity and grip strength.Patient-reported measures indicated marked reductions in neuropathic pain and paresthesia.No conduit-related adverse events or neuroma formation were observed.This case series highlights the potential of collagen-based conduits to promote robust axonal regeneration and functional restoration even in delayed presentations.By eliminating donor-site morbidity and simplifying the reconstructive procedure,conduit-assisted repair offers a less invasive,reproducible alternative to autologous grafts for both acute and chronic peripheral nerve injuries.展开更多
The repair of peripheral nerve injuries with autologous nerve remains the gold standard （Wang et al., 2005; Yao et al., 2010; Deal et al., 2012; Kriebel et al., 2014; Liu et al., 2014; Tamaki et al., 2014; Yu et al.,...The repair of peripheral nerve injuries with autologous nerve remains the gold standard （Wang et al., 2005; Yao et al., 2010; Deal et al., 2012; Kriebel et al., 2014; Liu et al., 2014; Tamaki et al., 2014; Yu et al., 2014; Zhu and Lou, 2014）. With advances in tissue engineering and biomaterials, tissue-engineered nerve conduits with various biomaterials and structures, such as collagen and chitosan nerve conduits, have already been used in the clinic as alternatives to autologous nerve in the repair of peripheral nerve injury （Wang et al., 2012; Svizenska et al., 2013; Eppenberger et al., 2014; Gu et al., 2014; Koudehi et al., 2014; MoyaDiaz et al., 2014; Novajra et al., 2014; Okamoto et al., 2014; Shea et al., 2014; Singh et al., 2014; Tamaki et al., 2014; Yu et al., 2014）. Therefore, new simple and effective methods展开更多
Peripheral nerve injuries are common in clinical practice because of traumas such as crushing and sectioning. Lesions of the nerve structure result in lost or diminished sensitivity and/or motor activity in the innerv...Peripheral nerve injuries are common in clinical practice because of traumas such as crushing and sectioning. Lesions of the nerve structure result in lost or diminished sensitivity and/or motor activity in the innervated territory. The degree of lesion depends on the specific nerve involved, the magnitude and type of pres- sure exerted, and the duration of the compression. The results of such injuries commonly include axonal degeneration and retro- grade degeneration of the corresponding neurons in the spinal medulla, followed by very slow regeneration （Rochkind et al., 2001）. The adverse effects on the daily activities of patients with a peripheral nerve injury are a determining factor in establishing the goals of early recovery （Rodriguez et al., 2004）.展开更多
Peripheral nerve injury is a common disease that endangers human health.There is a variety of methods to repair peripheral nerve injury,the current"gold standard"approach is autograft,however it still faces ...Peripheral nerve injury is a common disease that endangers human health.There is a variety of methods to repair peripheral nerve injury,the current"gold standard"approach is autograft,however it still faces many disadvantages.A new choice is the use of artificial nerve conduits,which are tubular structures and are designed to bridge nerve gaps.In order to bridge longer nerve gaps and gain ideal nerve regeneration effects,multiple technologies have been developed to the design of nerve conduits,such as selecting sutible materials,supplementing growth factors,transplanting supporting cells and so on.This review mainly introduce current progess in growth factors supplementation and supporting cells transplantation technology of nerve conduits.展开更多
We previously combined reduced graphene oxide(rGO)with gelatin-methacryloyl(GelMA)and polycaprolactone(PCL)to create an rGO-GelMA-PCL nerve conduit and found that the conductivity and biocompatibility were improved.Ho...We previously combined reduced graphene oxide(rGO)with gelatin-methacryloyl(GelMA)and polycaprolactone(PCL)to create an rGO-GelMA-PCL nerve conduit and found that the conductivity and biocompatibility were improved.However,the rGO-GelMA-PCL nerve conduits differed greatly from autologous nerve transplants in their ability to promote the regeneration of injured peripheral nerves and axonal sprouting.Extracellular vesicles derived from bone marrow mesenchymal stem cells(BMSCs)can be loaded into rGO-GelMA-PCL nerve conduits for repair of rat sciatic nerve injury because they can promote angiogenesis at the injured site.In this study,12 weeks after surgery,sciatic nerve function was measured by electrophysiology and sciatic nerve function index,and myelin sheath and axon regeneration were observed by electron microscopy,immunohistochemistry,and immunofluorescence.The regeneration of microvessel was observed by immunofluorescence.Our results showed that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles were superior to rGO-GelMA-PCL conduits alone in their ability to increase the number of newly formed vessels and axonal sprouts at the injury site as well as the recovery of neurological function.These findings indicate that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles can promote peripheral nerve regeneration and neurological function recovery,and provide a new direction for the curation of peripheral nerve defect in the clinic.展开更多
OBJECTIVE： To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL： Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair...OBJECTIVE： To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL： Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. SELECTION CRITERIA： Inclusion criteria： peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria： articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. MAIN OUTCOME MEASURES： （a） Annual publication output; （b） publication type; （c） publication by research field; （d） publication by journal; （e） publication by funding agency; （f） publication by author; （g） publication by country and institution; （h） publications by institution in China; （i） most-cited papers. RESULTS： A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurge and Joumal of Biomedical Materials Research PartA. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. CONCLUSION： Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.展开更多
Silk can promote the penetration of oxygen and water and support the attachment and proliferation of neurons and Schwann cells,and has appropriate biodegradation kinetics and flexible physical strength.It is a high-qu...Silk can promote the penetration of oxygen and water and support the attachment and proliferation of neurons and Schwann cells,and has appropriate biodegradation kinetics and flexible physical strength.It is a high-quality natural tissue engineering material and can be used as an ideal matrix for nerve repair.This paper reviewed the structure and properties of silk and the research progress of silk nerve conduits in peripheral nerve regeneration in recent years,and prospected its clinical application.展开更多
Large-gap nerve defects require nerve guide conduits(NGCs)for complete regeneration and muscle innervation.Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon...Large-gap nerve defects require nerve guide conduits(NGCs)for complete regeneration and muscle innervation.Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon regeneration.Still,most are tubular with inadequate pore sizes and lack surface cues for nutrient transport,cell attachment,and tissue infiltration.This study developed a porous spiral NGC to address these issues using a 3D-printed thermoplastic polyurethane(TPU)fiber lattice.The lattice was functionalized with poly(3-hydroxybutyrate-co-3-hydroxyvalerate)(PHBV)electrospun aligned(aPHBV)and randomly(rPHBV)oriented nanofibers to enhance cellular activity.TPU lattices were made with 25%,35%,and 50%infill densities to create scaffolds with varied mechanical compliance.The fabricated TPU/PHBV spiral conduits had significantly higher surface areas(25%TPU/PHBV:698.97 mm^(2),35%TPU/PHBV:500.06 mm^(2),50%TPU/PHBV:327.61 mm^(2))compared to commercially available nerve conduits like Neurolac™(205.26 mm^(2)).Aligned PHBV nanofibers showed excellent Schwann cell(RSC96)adhesion,proliferation,and neurogenic gene expression for all infill densities.Spiral TPU/PHBV conduits with 25%and 35%infill densities exhibited Young’s modulus values comparable to Neurotube®and ultimate tensile strength like acellular cadaveric human nerves.A 10 mm sciatic nerve defect in Wistar rats treated with TPU/aPHBV NGCs demonstrated muscle innervation and axon healing comparable to autografts over 4 months,as evaluated by gait analysis,functional recovery,and histology.The TPU/PHBV NGC developed in this study shows promise as a treatment for large-gap nerve defects.展开更多
Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the ...Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.展开更多
Porous multi-channel chitosan conduits were fabricated using a novel phase-separation technique with an axial temperature gradient. First, porous chitosan tubes were made with a mold that was composed of two concentri...Porous multi-channel chitosan conduits were fabricated using a novel phase-separation technique with an axial temperature gradient. First, porous chitosan tubes were made with a mold that was composed of two concentric polytetrafiuoroethylene tubes. Then 1%-3% （w/v） chitosan solution was injected into the chitosan tube while the two ends of the tube were closed with steel rods. Then the outside of the tube was wrapped with a layer of thermal insulating material to reduce the heat transfer through the outside, and the tubes were placed in a freezer. The resulting phase separation then occurred in the presence of an axial temperature gradient. The porosity, microtubule diameter, and orientation were controlled by adjusting the polymer concentration and temperature gradient. After the preparation course, no poisonous substances remained on the conduits. The mechanical properties, swelling, and biodegradability of the chitosan conduits were investigated, and a scanning electron microscope was used to observe the tubular morphology and growth of neuroblastoma cells （N2A, mouse） in the conduits. The results demonstrate that the multi-channel chitosan conduits have suitable mechanical strength, swelling, degradation properties, and nerve cell affinity, so they hold promise for use as neural tissue engineering scaffolds.展开更多
Exosomes derived from mesenchymal stem cells are of therapeutic interest because of their important role in intracellular communication and biological regulation.On the basis of previously studied nerve conduits,we de...Exosomes derived from mesenchymal stem cells are of therapeutic interest because of their important role in intracellular communication and biological regulation.On the basis of previously studied nerve conduits,we designed a polydopamine-modified chitin conduit loaded with mesenchymal stem cell-derived exosomes that release the exosomes in a sustained and stable manner.In vitro experiments revealed that rat mesenchymal stem cell-derived exosomes enhanced Schwann cell proliferation and secretion of neurotrophic and growth factors,increased the expression of Jun and Sox2 genes,decreased the expression of Mbp and Krox20 genes in Schwann cells,and reprogrammed Schwann cells to a repair phenotype.Furthermore,mesenchymal stem cell-derived exosomes promoted neurite growth of dorsal root ganglia.The polydopamine-modified chitin conduits loaded with mesenchymal stem cell-derived exosomes were used to bridge 2 mm rat sciatic nerve defects.Sustained release of exosomes greatly accelerated nerve healing and improved nerve function.These findings confirm that sustained release of mesenchymal stem cell-derived exosomes loaded into polydopamine-modified chitin conduits promotes the functional recovery of injured peripheral nerves.展开更多
Using nerve guide conduits (NGCs) to promote the regeneration of PNI is a feasible alternative to autograft.Compared with NGCs made of single material,composite NGCs have a greater development prospect.Our previous re...Using nerve guide conduits (NGCs) to promote the regeneration of PNI is a feasible alternative to autograft.Compared with NGCs made of single material,composite NGCs have a greater development prospect.Our previous research has confirmed that poly(D,L-lactic acid)/β-tricalcium phosphate/hyaluronic acid/chitosan/nerve growth factor (PDLLA/β-TCP/HA/CHS/NGF) NGCs have excellent physical and chemical properties,which can slowly release NGF and support cell adhesion and proliferation.In this study,PDLLA/β-TCP/HA/CHS/NGF NGCs were prepared and used to bridge a 10 mm sciatic nerve defect in 200-250 g Sprague-Dawley (SD) rat to verify the performance of the NGCs in vivo.Substantial improvements in nerve regeneration were observed after using the PDLLA/β-TCP/HA/CHS/NGF NGCs based on gross post-operation observation,triceps wet weight analysis and nerve histological assessment.In vivo studies illustrate that the PDLLA/β-TCP/HA/CHS/NGF sustained-release NGCs can effectively promote peripheral nerve regeneration,and the effect is similar to that of autograft.展开更多
Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in ra...Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa- line groups than in the nerve growth factor-microspheres and autologous nerve groups. Electro- physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di- ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits com- bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits.展开更多
Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the com-plexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are n...Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the com-plexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the au-tologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit.展开更多
Our previous studies have histomorphologically confirmed that nanofibrous poly（3-hydroxybutyrate- co-3-hydroxyvalerate） conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on ...Our previous studies have histomorphologically confirmed that nanofibrous poly（3-hydroxybutyrate- co-3-hydroxyvalerate） conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on rat behaviors remain poorly understood. In this study, we used nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous sciatic nerve to bridge 30-ram-long rat sciatic nerve gaps. Within 4 months after surgery, rat sciatic nerve functional re- covery was evaluated per month by behavioral analyses, including toe out angle, toe spread anal- ysis, walking track analysis, extensor postural thrust, swimming test, open-field analysis and no- ciceptive function. Results showed that rat sciatic nerve functional recovery was similar after nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous nerve grafting. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit is suitable in use for repair of long-segment sciatic nerve defects.展开更多
Nerve conduits have been identified as one of the most promising treatments for peripheral nerve injuries,yet it remains unsolved how to develop ideal nerve conduits with both appropriate biological and mechanical pro...Nerve conduits have been identified as one of the most promising treatments for peripheral nerve injuries,yet it remains unsolved how to develop ideal nerve conduits with both appropriate biological and mechanical properties.Existing nerve conduits must make trade-offs between mechanical strength and biocompatibility.Here,we propose a multi-nozzle additive-lathe 3D bioprinting technology to fabricate a bilayered nerve conduit.The materials for printing consisted of gelatin methacrylate(GelMA)-based inner layer,which was cellularized with bone marrow mesenchymal stem cells(BMSCs)and GelMA/poly(ethylene glycol)diacrylate(PEGDA)-based outer layer.The high viability and extensive morphological spreading of BMSCs encapsulated in the inner layer was achieved by adjusting the degree of methacryloyl substitution and the concentration of GelMA.Strong mechanical performance of the outer layer was obtained by the addition of PEGDA.The performance of the bilayered nerve conduits was assessed using in vitro culture of PC12 cells.The cell density of PC12 cells attached to cellularized bilayered nerve conduits was more than 4 times of that on acellular bilayered nerve conduits.The proliferation rate of PC12 cells attached to cellularized bilayered nerve conduits was over 9 times higher than that on acellular bilayered nerve conduits.These results demonstrate the additive-lathe 3D bioprinting of BMSCs embedded bilayered nerve conduits holds great potential in facilitating peripheral nerve repair.展开更多
Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate...Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits(biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy.S-100(Schwann cell marker) and CD4(inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China(La-1031218) on October 2, 2014.展开更多
We have designed a novel nerve guidance conduit（NGC） made from silk fibroin and poly（lactic-co-glycolic acid） through electrospinning and weaving（ESP-NGCs）. Several physical and biological properties of the ESP-...We have designed a novel nerve guidance conduit（NGC） made from silk fibroin and poly（lactic-co-glycolic acid） through electrospinning and weaving（ESP-NGCs）. Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application.展开更多
Given the anatomic complexity at the bifurcation point of a nerve trunk,enforced suturing between stumps can lead to misdirection of nerve axons,thereby resulting in adverse consequences.We assumed that Y-tube conduit...Given the anatomic complexity at the bifurcation point of a nerve trunk,enforced suturing between stumps can lead to misdirection of nerve axons,thereby resulting in adverse consequences.We assumed that Y-tube conduits injected with human umbilical cord stem cells could be an effective method to solve such problems,but studies focused on the best type of Y-tube conduit remain controversial.Therefore,the present study evaluated the applicability and efficacy of various types of Y-tube conduits containing human umbilical cord stem cells for treating rat femoral nerve defects on their bifurcation points.At 12 weeks after the bridging surgery that included treatment with different types of Y-tube conduits,there were no differences in quadriceps femoris muscle weight or femoral nerve ultrastructure.However,the Y-tube conduit group with longer branches and a short trunk resulted in a better outcome according to retrograde labeling and electrophysiological analysis.It can be concluded from the study that repairing a mixed nerve defect at its bifurcation point with Y-tube conduits,in particular those with long branches and a short trunk,is effective and results in good outcomes.展开更多
Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduit...Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.展开更多
文摘Traumatic peripheral nerve injuries are a major contributor to long-term disability,accounting for nearly half of all peripheral nervous system disorders.Although autologous nerve grafting remains the clinical gold standard,it is limited by donor-site morbidity and often fails to achieve full functional recovery.Biodegradable collagen conduits have emerged as an appealing alternative,providing a scaffold for directed axonal growth without requiring graft harvest.We reported three cases of chronic nerve injuries(6-12 months post-trauma):two involving 2.0-3.5 cm ulnar nerve defects in the forearm and one with a 2.5 cm median nerve defect at the wrist.Under microscopic guidance,each defect was bridged with a tubular type I collagen conduit secured by epineurial sutures,followed by standardized physiotherapy and sensory reeducation.At 12-18 months of follow-up,all patients demonstrated near-complete sensory recovery—two-point discrimination and Semmes-Weinstein thresholds returned to≤6 mm—and motor function improved to Medical Research Council grades 4-5,restoring fine dexterity and grip strength.Patient-reported measures indicated marked reductions in neuropathic pain and paresthesia.No conduit-related adverse events or neuroma formation were observed.This case series highlights the potential of collagen-based conduits to promote robust axonal regeneration and functional restoration even in delayed presentations.By eliminating donor-site morbidity and simplifying the reconstructive procedure,conduit-assisted repair offers a less invasive,reproducible alternative to autologous grafts for both acute and chronic peripheral nerve injuries.
基金supported by the National High Technology Research and Development Program of China,No.2012AA020502the National Natural Science Foundation of China,No.81171457 and 81371687the Priority of Academic Program Development of Jiangsu Higher Education Institutions
文摘The repair of peripheral nerve injuries with autologous nerve remains the gold standard （Wang et al., 2005; Yao et al., 2010; Deal et al., 2012; Kriebel et al., 2014; Liu et al., 2014; Tamaki et al., 2014; Yu et al., 2014; Zhu and Lou, 2014）. With advances in tissue engineering and biomaterials, tissue-engineered nerve conduits with various biomaterials and structures, such as collagen and chitosan nerve conduits, have already been used in the clinic as alternatives to autologous nerve in the repair of peripheral nerve injury （Wang et al., 2012; Svizenska et al., 2013; Eppenberger et al., 2014; Gu et al., 2014; Koudehi et al., 2014; MoyaDiaz et al., 2014; Novajra et al., 2014; Okamoto et al., 2014; Shea et al., 2014; Singh et al., 2014; Tamaki et al., 2014; Yu et al., 2014）. Therefore, new simple and effective methods
文摘Peripheral nerve injuries are common in clinical practice because of traumas such as crushing and sectioning. Lesions of the nerve structure result in lost or diminished sensitivity and/or motor activity in the innervated territory. The degree of lesion depends on the specific nerve involved, the magnitude and type of pres- sure exerted, and the duration of the compression. The results of such injuries commonly include axonal degeneration and retro- grade degeneration of the corresponding neurons in the spinal medulla, followed by very slow regeneration （Rochkind et al., 2001）. The adverse effects on the daily activities of patients with a peripheral nerve injury are a determining factor in establishing the goals of early recovery （Rodriguez et al., 2004）.
基金Chinaprovince(2020376249,2019326481)the Natural Science Foundation of Ningbo(2013A6102647,2015A610207)。
文摘Peripheral nerve injury is a common disease that endangers human health.There is a variety of methods to repair peripheral nerve injury,the current"gold standard"approach is autograft,however it still faces many disadvantages.A new choice is the use of artificial nerve conduits,which are tubular structures and are designed to bridge nerve gaps.In order to bridge longer nerve gaps and gain ideal nerve regeneration effects,multiple technologies have been developed to the design of nerve conduits,such as selecting sutible materials,supplementing growth factors,transplanting supporting cells and so on.This review mainly introduce current progess in growth factors supplementation and supporting cells transplantation technology of nerve conduits.
基金supported by the National Natural Science Foundation of China, No. 31671248the Natural Science Foundation of Beijing, No. 7222198 (both to NH)
文摘We previously combined reduced graphene oxide(rGO)with gelatin-methacryloyl(GelMA)and polycaprolactone(PCL)to create an rGO-GelMA-PCL nerve conduit and found that the conductivity and biocompatibility were improved.However,the rGO-GelMA-PCL nerve conduits differed greatly from autologous nerve transplants in their ability to promote the regeneration of injured peripheral nerves and axonal sprouting.Extracellular vesicles derived from bone marrow mesenchymal stem cells(BMSCs)can be loaded into rGO-GelMA-PCL nerve conduits for repair of rat sciatic nerve injury because they can promote angiogenesis at the injured site.In this study,12 weeks after surgery,sciatic nerve function was measured by electrophysiology and sciatic nerve function index,and myelin sheath and axon regeneration were observed by electron microscopy,immunohistochemistry,and immunofluorescence.The regeneration of microvessel was observed by immunofluorescence.Our results showed that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles were superior to rGO-GelMA-PCL conduits alone in their ability to increase the number of newly formed vessels and axonal sprouts at the injury site as well as the recovery of neurological function.These findings indicate that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles can promote peripheral nerve regeneration and neurological function recovery,and provide a new direction for the curation of peripheral nerve defect in the clinic.
文摘OBJECTIVE： To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL： Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. SELECTION CRITERIA： Inclusion criteria： peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria： articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. MAIN OUTCOME MEASURES： （a） Annual publication output; （b） publication type; （c） publication by research field; （d） publication by journal; （e） publication by funding agency; （f） publication by author; （g） publication by country and institution; （h） publications by institution in China; （i） most-cited papers. RESULTS： A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurge and Joumal of Biomedical Materials Research PartA. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. CONCLUSION： Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.
基金Supported by Development of Low-immunogenicity&Water-soluble Silk Fibroin(22541C)Chongqing Scientific Research Institution Performance Incentive Project(22529J and 22531J)Chongqing Rongchang Agriculture and Animal Husbandry High-tech Industry R&D Special Project(20209).
文摘Silk can promote the penetration of oxygen and water and support the attachment and proliferation of neurons and Schwann cells,and has appropriate biodegradation kinetics and flexible physical strength.It is a high-quality natural tissue engineering material and can be used as an ideal matrix for nerve repair.This paper reviewed the structure and properties of silk and the research progress of silk nerve conduits in peripheral nerve regeneration in recent years,and prospected its clinical application.
基金The authors wish to acknowledge Nano Mission,Department of Science&Technology(DST)(SR/NM/TP-83/2016(G))Prof.T.R.Rajagopalan R&D Cell of SASTRA Deemed University for financial and infrastructural support+4 种基金We also wish to acknowledge ATGC grant,Department of Biotechnology(DBT)(BT/ATGC/127/SP41147/2021)Adhoc funding,Indian Council of Medical Research(ICMR)(17x3/Adhoc/23/2022-ITR)DST SERB CRG(Exponential Technologies)grant(CRG/2021/007847)for financial supportfunding support provided by the National Institutes of Health(#R01NS134604,#R01EB034202,#R01AR078908,and#R01EB030060)the U.S.Army Medical Research Acquisition Activity(USAMRAA)through the CDMRP Peer-Reviewed Medical Research Program(Award No.W81XWH2010321,PR230581,and HT94252410137).
文摘Large-gap nerve defects require nerve guide conduits(NGCs)for complete regeneration and muscle innervation.Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon regeneration.Still,most are tubular with inadequate pore sizes and lack surface cues for nutrient transport,cell attachment,and tissue infiltration.This study developed a porous spiral NGC to address these issues using a 3D-printed thermoplastic polyurethane(TPU)fiber lattice.The lattice was functionalized with poly(3-hydroxybutyrate-co-3-hydroxyvalerate)(PHBV)electrospun aligned(aPHBV)and randomly(rPHBV)oriented nanofibers to enhance cellular activity.TPU lattices were made with 25%,35%,and 50%infill densities to create scaffolds with varied mechanical compliance.The fabricated TPU/PHBV spiral conduits had significantly higher surface areas(25%TPU/PHBV:698.97 mm^(2),35%TPU/PHBV:500.06 mm^(2),50%TPU/PHBV:327.61 mm^(2))compared to commercially available nerve conduits like Neurolac™(205.26 mm^(2)).Aligned PHBV nanofibers showed excellent Schwann cell(RSC96)adhesion,proliferation,and neurogenic gene expression for all infill densities.Spiral TPU/PHBV conduits with 25%and 35%infill densities exhibited Young’s modulus values comparable to Neurotube®and ultimate tensile strength like acellular cadaveric human nerves.A 10 mm sciatic nerve defect in Wistar rats treated with TPU/aPHBV NGCs demonstrated muscle innervation and axon healing comparable to autografts over 4 months,as evaluated by gait analysis,functional recovery,and histology.The TPU/PHBV NGC developed in this study shows promise as a treatment for large-gap nerve defects.
基金supported by the Lorenz B?hler Fonds,#2/19 (obtained by the Neuroregeneration Group,Ludwig Boltzmann Institute for Traumatology)the City of Vienna project ImmunTissue,MA23#30-11 (obtained by the Department Life Science Engineering,University of Applied Sciences Technikum Wien)。
文摘Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.
基金Supported by the China Postdoctoral Science Foundation and the Tsinghua-Yue-Yuen Medical Science Fund
文摘Porous multi-channel chitosan conduits were fabricated using a novel phase-separation technique with an axial temperature gradient. First, porous chitosan tubes were made with a mold that was composed of two concentric polytetrafiuoroethylene tubes. Then 1%-3% （w/v） chitosan solution was injected into the chitosan tube while the two ends of the tube were closed with steel rods. Then the outside of the tube was wrapped with a layer of thermal insulating material to reduce the heat transfer through the outside, and the tubes were placed in a freezer. The resulting phase separation then occurred in the presence of an axial temperature gradient. The porosity, microtubule diameter, and orientation were controlled by adjusting the polymer concentration and temperature gradient. After the preparation course, no poisonous substances remained on the conduits. The mechanical properties, swelling, and biodegradability of the chitosan conduits were investigated, and a scanning electron microscope was used to observe the tubular morphology and growth of neuroblastoma cells （N2A, mouse） in the conduits. The results demonstrate that the multi-channel chitosan conduits have suitable mechanical strength, swelling, degradation properties, and nerve cell affinity, so they hold promise for use as neural tissue engineering scaffolds.
基金supported by the National Natural Science Foundation of China,Nos.31771322,31571235the National Science Foundation of Beijing,No.7212121+3 种基金Beijing Science Technology New Star Cross Subject,No.2018019Science and Technology Plan Project of Shenzhen,No.JCYJ 20190806162205278the Key Laboratory of Trauma and Neural Regeneration(Peking University),Ministry of Educationa grant from National Center for Trauma Medicine,No.BMU2020XY005-01(all to PXZ).
文摘Exosomes derived from mesenchymal stem cells are of therapeutic interest because of their important role in intracellular communication and biological regulation.On the basis of previously studied nerve conduits,we designed a polydopamine-modified chitin conduit loaded with mesenchymal stem cell-derived exosomes that release the exosomes in a sustained and stable manner.In vitro experiments revealed that rat mesenchymal stem cell-derived exosomes enhanced Schwann cell proliferation and secretion of neurotrophic and growth factors,increased the expression of Jun and Sox2 genes,decreased the expression of Mbp and Krox20 genes in Schwann cells,and reprogrammed Schwann cells to a repair phenotype.Furthermore,mesenchymal stem cell-derived exosomes promoted neurite growth of dorsal root ganglia.The polydopamine-modified chitin conduits loaded with mesenchymal stem cell-derived exosomes were used to bridge 2 mm rat sciatic nerve defects.Sustained release of exosomes greatly accelerated nerve healing and improved nerve function.These findings confirm that sustained release of mesenchymal stem cell-derived exosomes loaded into polydopamine-modified chitin conduits promotes the functional recovery of injured peripheral nerves.
基金Funded by the Chinese National Natural Science Foundation (No. 51572206)the National Innovation and Entrepreneurship Training Program for College (Nos. 202110497032, 202110497033, and S202110497080)。
文摘Using nerve guide conduits (NGCs) to promote the regeneration of PNI is a feasible alternative to autograft.Compared with NGCs made of single material,composite NGCs have a greater development prospect.Our previous research has confirmed that poly(D,L-lactic acid)/β-tricalcium phosphate/hyaluronic acid/chitosan/nerve growth factor (PDLLA/β-TCP/HA/CHS/NGF) NGCs have excellent physical and chemical properties,which can slowly release NGF and support cell adhesion and proliferation.In this study,PDLLA/β-TCP/HA/CHS/NGF NGCs were prepared and used to bridge a 10 mm sciatic nerve defect in 200-250 g Sprague-Dawley (SD) rat to verify the performance of the NGCs in vivo.Substantial improvements in nerve regeneration were observed after using the PDLLA/β-TCP/HA/CHS/NGF NGCs based on gross post-operation observation,triceps wet weight analysis and nerve histological assessment.In vivo studies illustrate that the PDLLA/β-TCP/HA/CHS/NGF sustained-release NGCs can effectively promote peripheral nerve regeneration,and the effect is similar to that of autograft.
基金supported by the National Natural Science Foundation of China,No.30872898,81371116the Natural Science Foundation of Beijing,No.7132173
文摘Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa- line groups than in the nerve growth factor-microspheres and autologous nerve groups. Electro- physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di- ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits com- bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits.
文摘Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the com-plexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the au-tologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit.
基金supported by Tonekabon Branch,Islamic Azad University,Tonekabon,Iran,No.73/442453
文摘Our previous studies have histomorphologically confirmed that nanofibrous poly（3-hydroxybutyrate- co-3-hydroxyvalerate） conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on rat behaviors remain poorly understood. In this study, we used nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous sciatic nerve to bridge 30-ram-long rat sciatic nerve gaps. Within 4 months after surgery, rat sciatic nerve functional re- covery was evaluated per month by behavioral analyses, including toe out angle, toe spread anal- ysis, walking track analysis, extensor postural thrust, swimming test, open-field analysis and no- ciceptive function. Results showed that rat sciatic nerve functional recovery was similar after nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous nerve grafting. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit is suitable in use for repair of long-segment sciatic nerve defects.
基金the National Key Research and Development Program of China(Grant No.2018YFA0703000)the Key Research and Development Program of Zhejiang Province(Grants No.2017C01063,No.2017C01054)+1 种基金the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(Grant No.51821093)the Fundamental Research Funds for the Central Universities(Grant Nos.2019XZZX003‐02 and 2019FZA4002).
文摘Nerve conduits have been identified as one of the most promising treatments for peripheral nerve injuries,yet it remains unsolved how to develop ideal nerve conduits with both appropriate biological and mechanical properties.Existing nerve conduits must make trade-offs between mechanical strength and biocompatibility.Here,we propose a multi-nozzle additive-lathe 3D bioprinting technology to fabricate a bilayered nerve conduit.The materials for printing consisted of gelatin methacrylate(GelMA)-based inner layer,which was cellularized with bone marrow mesenchymal stem cells(BMSCs)and GelMA/poly(ethylene glycol)diacrylate(PEGDA)-based outer layer.The high viability and extensive morphological spreading of BMSCs encapsulated in the inner layer was achieved by adjusting the degree of methacryloyl substitution and the concentration of GelMA.Strong mechanical performance of the outer layer was obtained by the addition of PEGDA.The performance of the bilayered nerve conduits was assessed using in vitro culture of PC12 cells.The cell density of PC12 cells attached to cellularized bilayered nerve conduits was more than 4 times of that on acellular bilayered nerve conduits.The proliferation rate of PC12 cells attached to cellularized bilayered nerve conduits was over 9 times higher than that on acellular bilayered nerve conduits.These results demonstrate the additive-lathe 3D bioprinting of BMSCs embedded bilayered nerve conduits holds great potential in facilitating peripheral nerve repair.
基金supported by grants from the Taichung Veterans General Hospital and Central Taiwan University of Science and Technology,No.TCVGH-CTUST1047701(to CCS and BSL)Taichung Veterans General Hospital,No.TCVGH-1034907C(to CCS),Taiwan,China
文摘Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits(biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy.S-100(Schwann cell marker) and CD4(inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China(La-1031218) on October 2, 2014.
基金supported by the National Natural Science Foundation of China,No.81371687,81171457
文摘We have designed a novel nerve guidance conduit（NGC） made from silk fibroin and poly（lactic-co-glycolic acid） through electrospinning and weaving（ESP-NGCs）. Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application.
基金funded by the National High Technology Research and Development Program of China ("863" Program,No.2012AA020905)the National Natural Science Foundation of China (No.81360194)the National Basic Research Program of China (973 program,No.2014CB542200)
文摘Given the anatomic complexity at the bifurcation point of a nerve trunk,enforced suturing between stumps can lead to misdirection of nerve axons,thereby resulting in adverse consequences.We assumed that Y-tube conduits injected with human umbilical cord stem cells could be an effective method to solve such problems,but studies focused on the best type of Y-tube conduit remain controversial.Therefore,the present study evaluated the applicability and efficacy of various types of Y-tube conduits containing human umbilical cord stem cells for treating rat femoral nerve defects on their bifurcation points.At 12 weeks after the bridging surgery that included treatment with different types of Y-tube conduits,there were no differences in quadriceps femoris muscle weight or femoral nerve ultrastructure.However,the Y-tube conduit group with longer branches and a short trunk resulted in a better outcome according to retrograde labeling and electrophysiological analysis.It can be concluded from the study that repairing a mixed nerve defect at its bifurcation point with Y-tube conduits,in particular those with long branches and a short trunk,is effective and results in good outcomes.
基金supported by the National Natural Science Foundation of China,No.82202718the Natural Science Foundation of Beijing,No.L212050the China Postdoctoral Science Foundation,Nos.2019M664007,2021T140793(all to ZL)。
文摘Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.
