Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas.These lesions have been recognized as one of the three major precancer...Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas.These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010.In 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 IPNBs.IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis.From a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs.The histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin.Due to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging features.Surgical resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.展开更多
Polypyrrole (PPy) is a biocompatible polymer with good conductivity. Studies combining PPy with electrospinning have been reported; however, the associated decrease in PPy conductivity has not yet been resolved. We ...Polypyrrole (PPy) is a biocompatible polymer with good conductivity. Studies combining PPy with electrospinning have been reported; however, the associated decrease in PPy conductivity has not yet been resolved. We embedded PPy into poly(lactic acid) (PLA) nanofibers via electrospinning and fabricated a PLA/PPy nanofibrous scaffold containing 15% PPy with sustained conductivity and aligned topog- raphy, qhere was good biocompatibility between the scaffold and human umbilical cord mesenchymal stem cells as well as Schwann cells. Additionally, the direction of cell elongation on the scaffold was parallel to the direction of fibers. Our findings suggest that the aligned PLA/PPy nanofibrous scaffold is a promising biomaterial for peripheral nerve regeneration.展开更多
Extensive lesions involving the posterior quadrant of the cerebral hemisphere (temporal, parietal, and occipital lobes) induce intractable epilepsy. These patients are potential candidates for surgical treatmenttu. ...Extensive lesions involving the posterior quadrant of the cerebral hemisphere (temporal, parietal, and occipital lobes) induce intractable epilepsy. These patients are potential candidates for surgical treatmenttu. Maintenance of isolated nerve tissue activity after surgery plays a crucial role in the neuroprotective effects of neurosurgery treatment. Disconnection surgery of the posterior quadrant is used to completely isolate nerve fibers, while blood supply at the isolated lobes is maintained. Subsequently, cavities caused by cystic or necrotic nerve tissues should be reduced as much as possible,展开更多
BACKGROUND: Silicone tube bridging for peripheral nerve defects has been shown to be successful in guiding neural regeneration. However, this method is accompanied by complications. Because materials for bridging ner...BACKGROUND: Silicone tube bridging for peripheral nerve defects has been shown to be successful in guiding neural regeneration. However, this method is accompanied by complications. Because materials for bridging nerve fibers should exhibit biocompatibility, the development of novel artificial tissues to bridge nerve grafts has become important in the field of nerve tissue engineering for the repair of peripheral nerve defects. OBJECTIVE: To investigate effectiveness and feasibility of fascial pedicle artificial nerve tissue to repair peripheral nerve defects, and to compare to autologous nerve grafts and silicone tube bridging methods. DESIGN, TIME AND SETTING: Randomized, controlled, neural tissue engineering-based, animal experiments were performed at the Laboratory of Human Anatomy in Qingdao University Medical College from March 2006 to March 2007. MATERIALS: Medical absorbable collagen sponge was purchased from Henan Province Tiangong BJo-Material, China. Cantata 2-track 4-trace EMG-evoked potential instrument was purchased from Dantec, Denmark. Medical silicone tube was purchased from Shenzhen Legend Technology, China. METHODS: Forty healthy, adult, male, Sprague Dawley rats were randomly assigned to four groups fascial pedicle nerve, autologous nerve, silicone tube, and normal, with 10 rats in each group. A 10-mm defective sciatic nerve section was produced in rats following the removal of the fascial pedicle. The fascial flap surrounding the defect was harvested; one side of the nerve pedicle was maintained and then sutured into a tube with the fascia surface as the pipe inner wail. The tube was filled with a medical absorbable collagen (Bodyin) to construct a bridge between the artificial tissue nerve graft and the damaged sciatic nerve. The sciatic nerve defects in the autologous nerve and silicone tube groups were bridged using autologous nerve grafts and a medical silicone tube with matched specifications. MAIN OUTCOME MEASURES: At 4 months after transplantation, electromyogram was used to detect sciatic nerve conduction velocity and action potential amplitude. Hematoxylin-eosin and Nissl staining were used to determine the number of spinal cord anterior horn motor neurons and neurites Osmium tetroxide staining of the sciatic nerve bridge section was performed to detect the number and diameter of nerve fibers. RESULTS: There were no differences in sciatic nerve conduction velocity, action potential amplitude, the number of spinal cord anterior horn motor neurons and neurites, sciatic nerve fiber number, and diameter between the autologous nerve graft and normal groups (P 〉 0.05). However, these values were significantly greater than in the silicone tube group (P 〈 0.05). CONCLUSION: Quantitative results suggested that artificial nerve tissue, with an autologous tissue fascia flap as a nerve conduit, could be used to repair peripheral nerve defects. The regenerated fascial pedicle artificial nerve tissue was similar to an autologous nerve graft in terms of morphology and functional recovery and was superior to results from silicone tube bridging transplants.展开更多
Totally three articles focusing on "the effects of microenvironment for human amniotic epithelial cell transplantation on cell survival and differentiation, the migration of human amniotic epithelial cells after in v...Totally three articles focusing on "the effects of microenvironment for human amniotic epithelial cell transplantation on cell survival and differentiation, the migration of human amniotic epithelial cells after in vitro transplantation, and the rheological characteristics of anastomosing injured sciatic nerve with human amniotic membrane without amniotic epithelial cells" are published in three issues. We hope that our readers find these papers useful to their research.展开更多
Neural regeneration was once considered to be impossible, especially in the central nervous system where neural regeneration comprise the generation of new neurons, glia, axons, myelin, and synapses. Until recently, n...Neural regeneration was once considered to be impossible, especially in the central nervous system where neural regeneration comprise the generation of new neurons, glia, axons, myelin, and synapses. Until recently, neural stem cells/neural progenitor cells (NSCs/NPCs) were identified from various areas of brain and brought hopes to the neural repair and regeneration. Tissue engineering has revolutionized the current neural regeneration technology and it has become a pioneering interdisciplinary field in the areas of biomedical research. Polyhydoxyalkanoate (PHA) as one of biodegradable material has been successfully used as tissue engineering materials. It has also been applied in nerve tissue engineering due to the high biocompatibility and low cytotoxicity. Over the past 10 years, different kinds of modification strategies have been undertaken to improve the properties of PHA to fit the requirements from various fields. Several members of PHA family have been attempted for neural regeneration. This article reviewed the recent modification strategies for improving the properties of PHA and highlighted the pioneer applications in neural regeneration.展开更多
A micro-envioment for nerve cells and tissue growth were designed and constructed via surface modification of poly(L-lactide-co-glycolide)(PLGA) with chitosan and hydroxyapatire(HA). The poly(L_lactide-co-glyco...A micro-envioment for nerve cells and tissue growth were designed and constructed via surface modification of poly(L-lactide-co-glycolide)(PLGA) with chitosan and hydroxyapatire(HA). The poly(L_lactide-co-glycolide)/chitosan/hydroxyapatite (PLGA/chitosan/HA) conduits were manufactured by a combined solvent casting and particulate leaching technique. The conduits were highly porous with an interconnected pore structure and 76.5% porosity. Micropores with 50-100 micrometer diameter were formed in the conduits. In vivo application of PLGA/chitosan/HA conduits for reconstruction of 10 mm sciatic nerve defect was assessed by the walking track analysis, the quantifying of the wet weight of tibialis anterior muscle and the histological assessment. The conduits in host rats in vivo can not only be an effective in promoting regenerating of nerves but can also lead to favorable nerve functional recovery.展开更多
Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors derived from the neuroendocrine cell system,which that have increased in incidence and prevalence in recent years.Despite improvements in radiol...Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors derived from the neuroendocrine cell system,which that have increased in incidence and prevalence in recent years.Despite improvements in radiological and metabolic imaging,endoscopy still plays a pivotal role in the number of GEPNENs.Tumor detection,characterization,and staging are essential in management and treatment planning.Upper and lower gastrointestinal(GI)endoscopy is essential for correct localization of the primary tumor site of GI NENs.Endoscopic ultrasonography(EUS)has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors.Correct staging and histological diagnosis have important prognostic implications.Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall.Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors,thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery.Finally,locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.展开更多
BACKGROUND Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells.Of the different types of schwannomas,pelvic sciatic nerve schwannoma is extremely rare.Definite preoperative di...BACKGROUND Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells.Of the different types of schwannomas,pelvic sciatic nerve schwannoma is extremely rare.Definite preoperative diagnosis of pelvic schwannomas is difficult,and surgical resection is the gold standard for its definite diagnosis and treatment.CASE SUMMARY We present a case of pelvic schwannoma arising from the sciatic nerve that was detected in a 40-year-old man who underwent computed tomography for intermittent right lower back pain caused exclusively by a right ureteral calculus.Subsequently,successful transperitoneal laparoscopic surgery was performed for the intact removal of the stone and en bloc resection of the schwannoma.The total operative time was 125 min,and the estimated blood loss was inconspicuous.The surgical procedure was uneventful.The patient was discharged on postoperative day 5 with the simultaneous removal of the urinary catheter.However,the patient presented with motor and sensory disorders of the right lower limb,caused by partial damage to the right sciatic nerve.No tumor recurrence was observed at the postoperative appointment.CONCLUSION Histopathological examination of the specimen confirmed the diagnosis of a schwannoma.Thus,laparoscopic surgery is safe and feasible for concomitant extirpation of pelvic schwannomas and other pelvic and abdominal diseases that require surgical treatment.展开更多
Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration.However,morphological assessments of retinorecipient regions are...Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration.However,morphological assessments of retinorecipient regions are limited by the opacity of brain tissue.In this study,we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury.Specifically,we performed light-sheet imaging of whole brain tissue after a clearing process.We found that pseudorabies virus 724(PRV724)mostly infected retinal ganglion cells,and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains.Unexpectedly,PRV724-traced neurons were more widely distributed compared with data from previous studies.We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus,intergeniculate leaflet,ventral lateral geniculate nucleus,central amygdala,basolateral amygdala,Edinger-Westphal nucleus,and oculomotor nucleus,but not the superior vestibular nucleus,red nucleus,locus coeruleus,gigantocellular reticular nucleus,or facial nerve nucleus.Our findings demonstrate that the tissue clearing technique,combined with retrograde trans-synaptic viral tracing,can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury.Thus,our approach may be useful for future estimations of optic nerve injury and regeneration.展开更多
Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal c...Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.展开更多
Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI ...Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous trans-plantation ability.This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI.The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury.BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors,extracellular matrix molecules,and adhesion molecules.Additionally,BMSCs release pro-angiogenic factors to promote the formation of new blood vessels.They modulate cytokine expression and regulate macrophage polarization,leading to immunomodulation.Furthermore,BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration,thereby promoting neuronal repair and regeneration.Moreover,this review explores methods of applying BMSCs in PNI treatment,including direct cell trans-plantation into the injured neural tissue,implantation of BMSCs into nerve conduits providing support,and the application of genetically modified BMSCs,among others.These findings confirm the potential of BMSCs in treating PNI.However,with the development of this field,it is crucial to address issues related to BMSC therapy,including establishing standards for extracting,identifying,and cultivating BMSCs,as well as selecting application methods for BMSCs in PNI such as direct transplantation,tissue engineering,and genetic engineering.Addressing these issues will help translate current preclinical research results into clinical practice,providing new and effective treatment strategies for patients with PNI.展开更多
Background Peripheral nerve regeneration across large gaps is clinically challenging. Scaffold design plays a pivotal role in nerve tissue engineering. Recently, nanofibrous scaffolds have proven a suitable environmen...Background Peripheral nerve regeneration across large gaps is clinically challenging. Scaffold design plays a pivotal role in nerve tissue engineering. Recently, nanofibrous scaffolds have proven a suitable environment for cell attachment and proliferation due to similarities of their physical properties to natural extracellular matrix. Poly(propylene carbonate) (PPC) nanofibrous scaffolds have been investigated for vascular tissue engineering. However, no reports exist of PPC nanofibrous scaffolds for nerve tissue engineering. This study aimed to evaluate the potential role of aligned and random PPC nanofibrous scaffolds as substrates for peripheral nerve tissue and cells in nerve tissue engineering. Methods Aligned and random PPC nanofibrous scaffolds were fabricated by electrospinning and their chemical characterization were carried out using scanning electron microscopy (SEM). Dorsal root ganglia (DRG) from Sprague-Dawley rats were cultured on the nanofibrous substrates for 7 days. Neurite outgrowth and Schwann-ceU migration from DRG were observed and quantified using immunocytochemistry and SEM. Schwann cells derived from rat sciatic nerves were cultured in electrospun PPC scaffold-extract fluid for 24, 48, 72 hours and 7 days. The viability of Schwann cells was evaluated by 3-[4,5-dimethyl(thiazol-2-yl)-2,5-diphenyl] tetrazolium bromide (M]-F) assay. Results The diameter of aligned and random fibers ranged between 800 nm and 1200 nm, and the thickness of the films was approximately 10-20 IJm. Quantification of aligned fiber films revealed approximately 90% alignment of all fibers along the longitudinal axis. However, with random fiber films, the alignment of fibers was random through all angle bins. Rat DRG explants were grown on PPC nanofiber films for up to 1 week. On the aligned fiber films, the majority of neurite outgrowth and Schwann cell migration from the DRG extended unidirectionally, parallel to the aligned fibers. However, on the random fiber films, neurite outgrowth and Schwann cell migration were randomly distributed. A comparison of cumulative neurite lengths from cultured DRGs indicated that neurites grew faster on aligned PPC films ((2537.6±987.3) μm) than randomly-distributed fibers ((493.5±50.6) μm). The average distance of Schwann cell migration on aligned PPC nanofibrous films ((2803.5±943.6) μm) were significantly greater than those on random fibers ((625.3±47.8) pm). The viability of Schwann cells cultured in aligned PPC scaffold extract fluid was not significantly different from that in the plain DMEM/F12 medium at all time points after seeding. Conclusions The aligned PPC nanofibrous film, but not the randomly-oriented fibers, significantly enhanced peripheral nerve regeneration in vitro, indicating the substantial role of topographical cues in stimulating endogenous nerve repair mechanisms. Aligned PPC nanofibrous scaffolds may be a promising biomaterial for nerve regeneration.展开更多
Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upreg...Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation.Conversely,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression.However,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker.In this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems.First,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards.The growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration process.Second,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining methods.Surprisingly,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and beyond.Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord.These findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these levels.Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection.These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury.展开更多
Electrospun nanofibers have gained widespreading interest for tissue engineering application. In the present study, ApF/P(LLA-CL) nanofibrous scaffolds were fabricated via electrospinning. The feasibility of the mat...Electrospun nanofibers have gained widespreading interest for tissue engineering application. In the present study, ApF/P(LLA-CL) nanofibrous scaffolds were fabricated via electrospinning. The feasibility of the material as tissue engineering nerve scaffold was investigated in vitro. The average diameter increased with decreasing the blend ratio of ApF to P(LLA-CL). Characterization of 13C NMR and FTIR clarified that there is no obvious chemical bond reaction between ApF and P(LLA-CL). The tensile strength and elongation at break increased with the content increase of P(LLA-CL). The surface hydrophilic property of nanofibrous scaffolds enhanced with the increased content of ApF. Cell viability studies with Schwann cells demonstrated that ApFIP(LLA-CL) blended nanofibrous scaffolds significantly promoted cell growth as compare to P(LLA-CL), especially when the weight ratio of ApF to P(LLA-CL) was 25:75. The present work provides a basis for further studies of this novel nanofibrous material (ApF/P(LLA-CL)) in peripheral nerve tissue repair or regeneration.展开更多
Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells(ADSPCs)in peripheral nerve recovery.Cultivation under hypoxia is considered to enhance the release of the regenerati...Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells(ADSPCs)in peripheral nerve recovery.Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs.This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned(2%oxygen for 72 hours)autologous ADSPCs(n=9).This treatment mode was compared with three others:fibrin conduit seeded with ADSPCs cultivated under normoxic conditions(n=9);non-cell-carrying conduit(n=9);and nerve autograft only(n=9).A 16-week follow-up included functional testing(sciatic functional index and static sciatic index)as well as postmortem muscle mass analyses and morphometric nerve evaluations(histology,g-ratio,axon density,and diameter).At 8 weeks,the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups,indicating faster functional regeneration.Furthermore,histologic evaluation showed significantly increased axon outgrowth/branching,axon density,remyelination,and a reduced relative connective tissue area.Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts.Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.展开更多
Peripheral nerve injuries(PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage,...Peripheral nerve injuries(PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts(ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts(TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems(DDS), co-administration of platelet-rich plasma(PRP), and pretreatment with chondroitinase ABC(Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix(ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia(DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.展开更多
In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination w...In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cells of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tissue-engineered nerves was similar to that after autologous nerve grafting, and was higher than that after repair with acellular nerve allografts. Immunohistochemical staining revealed that motor endplates with acetylcholinesterase-positive nerve fibers were orderly arranged in the middle and superior parts of the gastrocnemius muscle; regenerated nerve tracts and sprouted branches were connected with motor endplates, as shown by acetylcholinesterase histochemistry combined with silver staining. The wet weight ratio of the tibialis anterior muscle at the affected contralateral hind limb was similar to the sciatic nerve after repair with autologous nerve grafts, and higher than that after repair with acellular nerve allografts. The hind limb motor function at the affected side was significantly improved, indicating that acellular nerve allografts combined with bone marrow mesenchymal stem cell bridging could promote functional recovery of rats with sciatic nerve defects.展开更多
With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the...With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the repair of peripheral nerve injuries, in particular multiple injuries and largegap defects, must be chosen carefully. Various methods and materials for protecting the healthy tissue and repairing peripheral nerve injuries have been described, and each method or material has advantages and disadvantages. Recently, a large amount of research has been focused on tissue-engineered materials for the repair of peripheral nerve injuries. Using the keywords "peripheral nerve injury", "autotransplant", "nerve graft", and "biomaterial", we retrieved publications using tissue-engineered materials for the repair of peripheral nerve injuries appearing in the Web of Science from 2010 to 2014. The country with the most total publications was the USA. The institutions that were the most productive in this field include Hannover Medical School (Germany), Washington University (USA), and Nantong University (China). The total number of publications using tissue-engineered materials for the repair of peripheral nerve injuries grad- ually increased over time, as did the number of Chinese publications, suggesting that China has made many scientific contributions to this field of research.展开更多
Neural stem cells (NSCs) are currently considered as powerful candidate seeding cells for regeneration of both spinal cords and peripheral nerves. In this study, NSCs derived from fetal rat cortices were co-cultured...Neural stem cells (NSCs) are currently considered as powerful candidate seeding cells for regeneration of both spinal cords and peripheral nerves. In this study, NSCs derived from fetal rat cortices were co-cultured with chitosan to evaluate the cell affinity of this material. The results showed that NSCs grew and proliferated well on chitosan films and most of them differentiated into neuron-like cells after 4 days of culture. Then, molded and braided chitosan conduits were fabricated and characterized for their cytotoxicity, swelling, and mechanical properties. Both types of conduits had no cytotoxic effects on fibroblasts (L929 cells) or neuroblastoma (Neuro-2a) cells. The molded conduits are much softer and more flexible while the braided conduits possess much better mechanical properties, which suggests different potential applications.展开更多
文摘Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas.These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010.In 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 IPNBs.IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis.From a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs.The histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin.Due to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging features.Surgical resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.
基金financially supported by Tsinghua University Initiative Scientific Research Program,No.20131089199the National Key Research and Development Program of China,No.2016YFB0700802the National Program on Key Basic Research Project of China(973 Program),No.2012CB518106,2014CB542201
文摘Polypyrrole (PPy) is a biocompatible polymer with good conductivity. Studies combining PPy with electrospinning have been reported; however, the associated decrease in PPy conductivity has not yet been resolved. We embedded PPy into poly(lactic acid) (PLA) nanofibers via electrospinning and fabricated a PLA/PPy nanofibrous scaffold containing 15% PPy with sustained conductivity and aligned topog- raphy, qhere was good biocompatibility between the scaffold and human umbilical cord mesenchymal stem cells as well as Schwann cells. Additionally, the direction of cell elongation on the scaffold was parallel to the direction of fibers. Our findings suggest that the aligned PLA/PPy nanofibrous scaffold is a promising biomaterial for peripheral nerve regeneration.
基金The Science Fund of Health Bureau of Tianjin,No.2013KZ046
文摘Extensive lesions involving the posterior quadrant of the cerebral hemisphere (temporal, parietal, and occipital lobes) induce intractable epilepsy. These patients are potential candidates for surgical treatmenttu. Maintenance of isolated nerve tissue activity after surgery plays a crucial role in the neuroprotective effects of neurosurgery treatment. Disconnection surgery of the posterior quadrant is used to completely isolate nerve fibers, while blood supply at the isolated lobes is maintained. Subsequently, cavities caused by cystic or necrotic nerve tissues should be reduced as much as possible,
文摘BACKGROUND: Silicone tube bridging for peripheral nerve defects has been shown to be successful in guiding neural regeneration. However, this method is accompanied by complications. Because materials for bridging nerve fibers should exhibit biocompatibility, the development of novel artificial tissues to bridge nerve grafts has become important in the field of nerve tissue engineering for the repair of peripheral nerve defects. OBJECTIVE: To investigate effectiveness and feasibility of fascial pedicle artificial nerve tissue to repair peripheral nerve defects, and to compare to autologous nerve grafts and silicone tube bridging methods. DESIGN, TIME AND SETTING: Randomized, controlled, neural tissue engineering-based, animal experiments were performed at the Laboratory of Human Anatomy in Qingdao University Medical College from March 2006 to March 2007. MATERIALS: Medical absorbable collagen sponge was purchased from Henan Province Tiangong BJo-Material, China. Cantata 2-track 4-trace EMG-evoked potential instrument was purchased from Dantec, Denmark. Medical silicone tube was purchased from Shenzhen Legend Technology, China. METHODS: Forty healthy, adult, male, Sprague Dawley rats were randomly assigned to four groups fascial pedicle nerve, autologous nerve, silicone tube, and normal, with 10 rats in each group. A 10-mm defective sciatic nerve section was produced in rats following the removal of the fascial pedicle. The fascial flap surrounding the defect was harvested; one side of the nerve pedicle was maintained and then sutured into a tube with the fascia surface as the pipe inner wail. The tube was filled with a medical absorbable collagen (Bodyin) to construct a bridge between the artificial tissue nerve graft and the damaged sciatic nerve. The sciatic nerve defects in the autologous nerve and silicone tube groups were bridged using autologous nerve grafts and a medical silicone tube with matched specifications. MAIN OUTCOME MEASURES: At 4 months after transplantation, electromyogram was used to detect sciatic nerve conduction velocity and action potential amplitude. Hematoxylin-eosin and Nissl staining were used to determine the number of spinal cord anterior horn motor neurons and neurites Osmium tetroxide staining of the sciatic nerve bridge section was performed to detect the number and diameter of nerve fibers. RESULTS: There were no differences in sciatic nerve conduction velocity, action potential amplitude, the number of spinal cord anterior horn motor neurons and neurites, sciatic nerve fiber number, and diameter between the autologous nerve graft and normal groups (P 〉 0.05). However, these values were significantly greater than in the silicone tube group (P 〈 0.05). CONCLUSION: Quantitative results suggested that artificial nerve tissue, with an autologous tissue fascia flap as a nerve conduit, could be used to repair peripheral nerve defects. The regenerated fascial pedicle artificial nerve tissue was similar to an autologous nerve graft in terms of morphology and functional recovery and was superior to results from silicone tube bridging transplants.
文摘Totally three articles focusing on "the effects of microenvironment for human amniotic epithelial cell transplantation on cell survival and differentiation, the migration of human amniotic epithelial cells after in vitro transplantation, and the rheological characteristics of anastomosing injured sciatic nerve with human amniotic membrane without amniotic epithelial cells" are published in three issues. We hope that our readers find these papers useful to their research.
文摘Neural regeneration was once considered to be impossible, especially in the central nervous system where neural regeneration comprise the generation of new neurons, glia, axons, myelin, and synapses. Until recently, neural stem cells/neural progenitor cells (NSCs/NPCs) were identified from various areas of brain and brought hopes to the neural repair and regeneration. Tissue engineering has revolutionized the current neural regeneration technology and it has become a pioneering interdisciplinary field in the areas of biomedical research. Polyhydoxyalkanoate (PHA) as one of biodegradable material has been successfully used as tissue engineering materials. It has also been applied in nerve tissue engineering due to the high biocompatibility and low cytotoxicity. Over the past 10 years, different kinds of modification strategies have been undertaken to improve the properties of PHA to fit the requirements from various fields. Several members of PHA family have been attempted for neural regeneration. This article reviewed the recent modification strategies for improving the properties of PHA and highlighted the pioneer applications in neural regeneration.
基金Funded by the National Natural Science Foundation of China(No.50774096)
文摘A micro-envioment for nerve cells and tissue growth were designed and constructed via surface modification of poly(L-lactide-co-glycolide)(PLGA) with chitosan and hydroxyapatire(HA). The poly(L_lactide-co-glycolide)/chitosan/hydroxyapatite (PLGA/chitosan/HA) conduits were manufactured by a combined solvent casting and particulate leaching technique. The conduits were highly porous with an interconnected pore structure and 76.5% porosity. Micropores with 50-100 micrometer diameter were formed in the conduits. In vivo application of PLGA/chitosan/HA conduits for reconstruction of 10 mm sciatic nerve defect was assessed by the walking track analysis, the quantifying of the wet weight of tibialis anterior muscle and the histological assessment. The conduits in host rats in vivo can not only be an effective in promoting regenerating of nerves but can also lead to favorable nerve functional recovery.
文摘Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors derived from the neuroendocrine cell system,which that have increased in incidence and prevalence in recent years.Despite improvements in radiological and metabolic imaging,endoscopy still plays a pivotal role in the number of GEPNENs.Tumor detection,characterization,and staging are essential in management and treatment planning.Upper and lower gastrointestinal(GI)endoscopy is essential for correct localization of the primary tumor site of GI NENs.Endoscopic ultrasonography(EUS)has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors.Correct staging and histological diagnosis have important prognostic implications.Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall.Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors,thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery.Finally,locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.
文摘BACKGROUND Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells.Of the different types of schwannomas,pelvic sciatic nerve schwannoma is extremely rare.Definite preoperative diagnosis of pelvic schwannomas is difficult,and surgical resection is the gold standard for its definite diagnosis and treatment.CASE SUMMARY We present a case of pelvic schwannoma arising from the sciatic nerve that was detected in a 40-year-old man who underwent computed tomography for intermittent right lower back pain caused exclusively by a right ureteral calculus.Subsequently,successful transperitoneal laparoscopic surgery was performed for the intact removal of the stone and en bloc resection of the schwannoma.The total operative time was 125 min,and the estimated blood loss was inconspicuous.The surgical procedure was uneventful.The patient was discharged on postoperative day 5 with the simultaneous removal of the urinary catheter.However,the patient presented with motor and sensory disorders of the right lower limb,caused by partial damage to the right sciatic nerve.No tumor recurrence was observed at the postoperative appointment.CONCLUSION Histopathological examination of the specimen confirmed the diagnosis of a schwannoma.Thus,laparoscopic surgery is safe and feasible for concomitant extirpation of pelvic schwannomas and other pelvic and abdominal diseases that require surgical treatment.
基金supported by the National Natural Science Foundation of China,No.81870655(to MBY)。
文摘Successful establishment of reconnection between retinal ganglion cells and retinorecipient regions in the brain is critical to optic nerve regeneration.However,morphological assessments of retinorecipient regions are limited by the opacity of brain tissue.In this study,we used an innovative tissue cleaning technique combined with retrograde trans-synaptic viral tracing to observe changes in retinorecipient regions connected to retinal ganglion cells in mice after optic nerve injury.Specifically,we performed light-sheet imaging of whole brain tissue after a clearing process.We found that pseudorabies virus 724(PRV724)mostly infected retinal ganglion cells,and that we could use it to retrogradely trace the retinorecipient regions in whole tissue-cleared brains.Unexpectedly,PRV724-traced neurons were more widely distributed compared with data from previous studies.We found that optic nerve injury could selectively modify projections from retinal ganglion cells in the hypothalamic paraventricular nucleus,intergeniculate leaflet,ventral lateral geniculate nucleus,central amygdala,basolateral amygdala,Edinger-Westphal nucleus,and oculomotor nucleus,but not the superior vestibular nucleus,red nucleus,locus coeruleus,gigantocellular reticular nucleus,or facial nerve nucleus.Our findings demonstrate that the tissue clearing technique,combined with retrograde trans-synaptic viral tracing,can be used to objectively and comprehensively evaluate changes in mouse retinorecipient regions that receive projections from retinal ganglion cells after optic nerve injury.Thus,our approach may be useful for future estimations of optic nerve injury and regeneration.
文摘Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.
基金CAMS Innovation Fund for Medical Sciences,No.2022-I2M-C&T-B-034.
文摘Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous trans-plantation ability.This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI.The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury.BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors,extracellular matrix molecules,and adhesion molecules.Additionally,BMSCs release pro-angiogenic factors to promote the formation of new blood vessels.They modulate cytokine expression and regulate macrophage polarization,leading to immunomodulation.Furthermore,BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration,thereby promoting neuronal repair and regeneration.Moreover,this review explores methods of applying BMSCs in PNI treatment,including direct cell trans-plantation into the injured neural tissue,implantation of BMSCs into nerve conduits providing support,and the application of genetically modified BMSCs,among others.These findings confirm the potential of BMSCs in treating PNI.However,with the development of this field,it is crucial to address issues related to BMSC therapy,including establishing standards for extracting,identifying,and cultivating BMSCs,as well as selecting application methods for BMSCs in PNI such as direct transplantation,tissue engineering,and genetic engineering.Addressing these issues will help translate current preclinical research results into clinical practice,providing new and effective treatment strategies for patients with PNI.
基金This study was supported by grants from the Hi-Tech Research and Development Program of China ("863" Program, No. 2009AA03Z312), Beijing Natural Science Foundation (The oriented micro-structure, double-aligned nerve-derived extracellular matrix scaffolds promote peripheral nerve long defects regeneration).
文摘Background Peripheral nerve regeneration across large gaps is clinically challenging. Scaffold design plays a pivotal role in nerve tissue engineering. Recently, nanofibrous scaffolds have proven a suitable environment for cell attachment and proliferation due to similarities of their physical properties to natural extracellular matrix. Poly(propylene carbonate) (PPC) nanofibrous scaffolds have been investigated for vascular tissue engineering. However, no reports exist of PPC nanofibrous scaffolds for nerve tissue engineering. This study aimed to evaluate the potential role of aligned and random PPC nanofibrous scaffolds as substrates for peripheral nerve tissue and cells in nerve tissue engineering. Methods Aligned and random PPC nanofibrous scaffolds were fabricated by electrospinning and their chemical characterization were carried out using scanning electron microscopy (SEM). Dorsal root ganglia (DRG) from Sprague-Dawley rats were cultured on the nanofibrous substrates for 7 days. Neurite outgrowth and Schwann-ceU migration from DRG were observed and quantified using immunocytochemistry and SEM. Schwann cells derived from rat sciatic nerves were cultured in electrospun PPC scaffold-extract fluid for 24, 48, 72 hours and 7 days. The viability of Schwann cells was evaluated by 3-[4,5-dimethyl(thiazol-2-yl)-2,5-diphenyl] tetrazolium bromide (M]-F) assay. Results The diameter of aligned and random fibers ranged between 800 nm and 1200 nm, and the thickness of the films was approximately 10-20 IJm. Quantification of aligned fiber films revealed approximately 90% alignment of all fibers along the longitudinal axis. However, with random fiber films, the alignment of fibers was random through all angle bins. Rat DRG explants were grown on PPC nanofiber films for up to 1 week. On the aligned fiber films, the majority of neurite outgrowth and Schwann cell migration from the DRG extended unidirectionally, parallel to the aligned fibers. However, on the random fiber films, neurite outgrowth and Schwann cell migration were randomly distributed. A comparison of cumulative neurite lengths from cultured DRGs indicated that neurites grew faster on aligned PPC films ((2537.6±987.3) μm) than randomly-distributed fibers ((493.5±50.6) μm). The average distance of Schwann cell migration on aligned PPC nanofibrous films ((2803.5±943.6) μm) were significantly greater than those on random fibers ((625.3±47.8) pm). The viability of Schwann cells cultured in aligned PPC scaffold extract fluid was not significantly different from that in the plain DMEM/F12 medium at all time points after seeding. Conclusions The aligned PPC nanofibrous film, but not the randomly-oriented fibers, significantly enhanced peripheral nerve regeneration in vitro, indicating the substantial role of topographical cues in stimulating endogenous nerve repair mechanisms. Aligned PPC nanofibrous scaffolds may be a promising biomaterial for nerve regeneration.
基金financed by the Spanish"Plan Nacional de Investigación Cientifica,Desorrollo e Innovación Tecnológica,Ministerio de Economíay Competitividod(Instituto de Solud CarlosⅢ)",grant Nos:FIS PI17-0393,FIS PI20-0318co-financed by the"Fondo Europeo de Desorrollo Regional ERDF-FEDER European Union",grant No.P18-RT-5059+2 种基金by"Plan Andaluz de Investigación,Desarrollo e Innovación(PAIDI 2020)Consejerio de Transformoción Económico,Industria,Conocimiento y Universidades,Junta de Andolucío,Espa?a",and grant No.A-CTS-498-UGR18by"Programa Operotivo FEDER Andalucía 2014-2020,Universidod de Granada,Junta de Andalucía,Espa?a",ca-funded by ERDF-FEDER,the European Union(all to VC)。
文摘Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation.Conversely,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression.However,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker.In this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems.First,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards.The growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration process.Second,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining methods.Surprisingly,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and beyond.Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord.These findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these levels.Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection.These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury.
基金This research was supported by the National Key Research Program of China (2016YFA0201702 of 2016YFA0201700), the National Natural Science Foundation of China (Grant Nos. 31470941 and 31271035), the Science and Technology Commission of Shanghai Municipality (Grant Nos. 15JC1490100 and 15441905100), the Ph.D. Programs Foundation of Ministry of Education of China (Grant No. 20130075110005), and the Yantai Double Hundred Talent Plan. The authors extend their appreciation to the International Scientific Partnership Program 1SPP at King Saud University for funding this research work through ISPP# 0049.
文摘Electrospun nanofibers have gained widespreading interest for tissue engineering application. In the present study, ApF/P(LLA-CL) nanofibrous scaffolds were fabricated via electrospinning. The feasibility of the material as tissue engineering nerve scaffold was investigated in vitro. The average diameter increased with decreasing the blend ratio of ApF to P(LLA-CL). Characterization of 13C NMR and FTIR clarified that there is no obvious chemical bond reaction between ApF and P(LLA-CL). The tensile strength and elongation at break increased with the content increase of P(LLA-CL). The surface hydrophilic property of nanofibrous scaffolds enhanced with the increased content of ApF. Cell viability studies with Schwann cells demonstrated that ApFIP(LLA-CL) blended nanofibrous scaffolds significantly promoted cell growth as compare to P(LLA-CL), especially when the weight ratio of ApF to P(LLA-CL) was 25:75. The present work provides a basis for further studies of this novel nanofibrous material (ApF/P(LLA-CL)) in peripheral nerve tissue repair or regeneration.
基金support by the Faculty of Medicine,Ludwig-Maximilians-University(FöFoLe,Project 843 and 955,to TH and MMS).
文摘Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells(ADSPCs)in peripheral nerve recovery.Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs.This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned(2%oxygen for 72 hours)autologous ADSPCs(n=9).This treatment mode was compared with three others:fibrin conduit seeded with ADSPCs cultivated under normoxic conditions(n=9);non-cell-carrying conduit(n=9);and nerve autograft only(n=9).A 16-week follow-up included functional testing(sciatic functional index and static sciatic index)as well as postmortem muscle mass analyses and morphometric nerve evaluations(histology,g-ratio,axon density,and diameter).At 8 weeks,the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups,indicating faster functional regeneration.Furthermore,histologic evaluation showed significantly increased axon outgrowth/branching,axon density,remyelination,and a reduced relative connective tissue area.Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts.Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.
基金supported,in part,by a research grant from Baylor Scott&White Health Central Texas Foundation and NIH grant R01-NS067435(JHH)
文摘Peripheral nerve injuries(PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts(ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts(TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems(DDS), co-administration of platelet-rich plasma(PRP), and pretreatment with chondroitinase ABC(Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix(ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia(DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.
基金financially sponsored by the Natural Science Foundation of Liaoning Province,No.201102135
文摘In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cells of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tissue-engineered nerves was similar to that after autologous nerve grafting, and was higher than that after repair with acellular nerve allografts. Immunohistochemical staining revealed that motor endplates with acetylcholinesterase-positive nerve fibers were orderly arranged in the middle and superior parts of the gastrocnemius muscle; regenerated nerve tracts and sprouted branches were connected with motor endplates, as shown by acetylcholinesterase histochemistry combined with silver staining. The wet weight ratio of the tibialis anterior muscle at the affected contralateral hind limb was similar to the sciatic nerve after repair with autologous nerve grafts, and higher than that after repair with acellular nerve allografts. The hind limb motor function at the affected side was significantly improved, indicating that acellular nerve allografts combined with bone marrow mesenchymal stem cell bridging could promote functional recovery of rats with sciatic nerve defects.
文摘With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the repair of peripheral nerve injuries, in particular multiple injuries and largegap defects, must be chosen carefully. Various methods and materials for protecting the healthy tissue and repairing peripheral nerve injuries have been described, and each method or material has advantages and disadvantages. Recently, a large amount of research has been focused on tissue-engineered materials for the repair of peripheral nerve injuries. Using the keywords "peripheral nerve injury", "autotransplant", "nerve graft", and "biomaterial", we retrieved publications using tissue-engineered materials for the repair of peripheral nerve injuries appearing in the Web of Science from 2010 to 2014. The country with the most total publications was the USA. The institutions that were the most productive in this field include Hannover Medical School (Germany), Washington University (USA), and Nantong University (China). The total number of publications using tissue-engineered materials for the repair of peripheral nerve injuries grad- ually increased over time, as did the number of Chinese publications, suggesting that China has made many scientific contributions to this field of research.
基金Supported by the National Natural Science Foundation of China (No. 30400099), the National Key Basic Research and Develop-ment (973) Program of China (No. 2005CB623905), and the Tsinghua-Yue-Yuen Medical Science Fund
文摘Neural stem cells (NSCs) are currently considered as powerful candidate seeding cells for regeneration of both spinal cords and peripheral nerves. In this study, NSCs derived from fetal rat cortices were co-cultured with chitosan to evaluate the cell affinity of this material. The results showed that NSCs grew and proliferated well on chitosan films and most of them differentiated into neuron-like cells after 4 days of culture. Then, molded and braided chitosan conduits were fabricated and characterized for their cytotoxicity, swelling, and mechanical properties. Both types of conduits had no cytotoxic effects on fibroblasts (L929 cells) or neuroblastoma (Neuro-2a) cells. The molded conduits are much softer and more flexible while the braided conduits possess much better mechanical properties, which suggests different potential applications.