Delivery of chondroitinase ABC and glial cell line‐derived neurotrophic factor from silk fibroin conduits enhances peripheral nerve regeneration

Nerve conduits are a proven strategy for guiding axon regrowth following injury. This study compares degradable silk–trehalose films containing chondroitinase ABC (ChABC) and/or glial cell line‐derived neurotrophic factor (GDNF) loaded within a silk fibroin‐based nerve conduit in a rat sciatic nerve defect model. Four groups of silk conduits were prepared, with the following silk–trehalose films inserted into the conduit: (a) empty; (b) 1 µg GDNF; (3) 2 U ChABC; and (4) 1 µg GDNF/2 U ChABC. Drug release studies demonstrated 20% recovery of GDNF and ChABC at 6 weeks and 24 h, respectively. Six conduits of each type were implanted into 15 mm sciatic nerve defects in Lewis rats; conduits were explanted for histological analysis at 6 weeks. Tissues stained with Schwann cell S‐100 antibody demonstrated an increased density of cells in both GDNF‐ and ChABC‐treated groups compared to empty control conduits (p < 0.05). Conduits loaded with GDNF and ChABC also demonstrated higher levels of neuron‐specific PGP 9.5 protein when compared to controls (p < 0.05). In this study we demonstrated a method to enhance Schwann cell migration and proliferation and also foster axonal regeneration when repairing peripheral nerve gap defects. Silk fibroin‐based nerve conduits possess favourable mechanical and degradative properties and are further enhanced when loaded with ChABC and GDNF. Copyright © 2014 John Wiley & Sons, Ltd.     

Nanofibrous nerve conduit‐enhanced peripheral nerve regeneration

Fibre structures represent a potential class of materials for the formation of synthetic nerve conduits due to their biomimicking architecture. Although the advantages of fibres in enhancing nerve regeneration have been demonstrated, in vivo evaluation of fibre size effect on nerve regeneration remains limited. In this study, we analyzed the effects of fibre diameter of electrospun conduits on peripheral nerve regeneration across a 15‐mm critical defect gap in a rat sciatic nerve injury model. By using an electrospinning technique, fibrous conduits comprised of aligned electrospun poly (ε‐caprolactone) (PCL) microfibers (981 ± 83 nm, Microfiber) or nanofibers (251 ± 32 nm, Nanofiber) were obtained. At three months post implantation, axons regenerated across the defect gap in all animals that received fibrous conduits. In contrast, complete nerve regeneration was not observed in the control group that received empty, non‐porous PCL film conduits (Film). Nanofiber conduits resulted in significantly higher total number of myelinated axons and thicker myelin sheaths compared to Microfiber and Film conduits. Retrograde labeling revealed a significant increase in number of regenerated dorsal root ganglion sensory neurons in the presence of Nanofiber conduits (1.93 ± 0.71 × 10³ vs. 0.98 ± 0.30 × 10³ in Microfiber, p < 0.01). In addition, the compound muscle action potential (CMAP) amplitudes were higher and distal motor latency values were lower in the Nanofiber conduit group compared to the Microfiber group. This study demonstrated the impact of fibre size on peripheral nerve regeneration. These results could provide useful insights for future nerve guide designs. Copyright © 2012 John Wiley & Sons, Ltd.     

Functional recovery guided by an electrospun silk fibroin conduit after sciatic nerve injury in rats

The aim of this study was to evaluate the regenerative capacity of a newly developed nerve guidance conduit using electrospun silk fibroin (SFNC) implanted in a 10‐mm defect of the sciatic nerve in rats. After evaluating the physical properties and cytocompatibility of SFNC in vitro, rats were randomly allocated into three groups: defect only, autograft and SFNC. To compare motor function and abnormal sensation among groups, ankle stance angle (ASA) and severity of autotomy were observed for 10 weeks after injury. Immunostaining with axonal neurofilament (NF) and myelin basic protein (MBP) antibodies were performed to investigate regenerated nerve fibres inside SFNC. ASA increased significantly in the SFNC group at 1, 7 and 10 weeks after injury compared to the defect only group (p < 0.05). At one week, mean ASA of the SFNC group was significantly higher than that of the autograft group (p < 0.05). Onset and severity of autotomy decreased significantly in the SFNC group compared to other groups (p < 0.05). Autotomy in the SFNC group started at 4 weeks and maximally reached toe level. However, the defect only and autograft groups first showed autotomy at 2 and 1 weeks following injury, respectively, and then reached the sole level. Well myelinated nerve fibres stained with NF and MBP were found inside SFNC. In conclusion, SFNC could be helpful in restoring motor function and preventing abnormal sensations after nerve injury. Copyright © 2012 John Wiley & Sons, Ltd.     

Phosphate glass fibres promote neurite outgrowth and early regeneration in a peripheral nerve injury model

Three‐dimensional (3D) scaffolds, which are bioactive and aid in neuronal guidance, are essential in the repair and regeneration of injured peripheral nerves. In this study, we used novel inorganic microfibres guided by phosphate glass (PG). PG fibres (PGfs) were aligned on compressed collagen that was rolled into a nerve conduit. In vitro tests confirmed that adult dorsal root ganglion (DRG) neurons showed active neurite outgrowth along the fibres, with a maximum number and length of neurites being significantly higher than those cultured on tissue culture plastic. In vivo experiments with nerve conduits that either contained PGfs (PGf/Col) or lacked them (Col) were conducted on transected sciatic nerves of rats for up to 12 weeks. One week after implantation, the PGf/Col group showed many axons extending along the scaffold, whereas the Col group showed none. Eight weeks after implantation, the PGf/Col group exhibited greater recovery of plantar muscle atrophy than the Col group. Electrophysiological studies revealed that some animals in the PGf/Col group at 6 and 7 weeks post‐implantation (5.3% and 15.8%, respectively) showed compound muscle action potential. The Col group over the same period showed no response. Motor function also showed faster recovery in the PGf/Col group compared to the Col group up to 7 weeks. However, there was no significant difference in the number of axons, muscle atrophy or motor and sensory functions between the two groups at 12 weeks post‐implantation. In summary, phosphate glass fibres can promote directional growth of axons in cases of peripheral nerve injury by acting as physical guides. Copyright © 2012 John Wiley & Sons, Ltd.     

Detergent‐based decellularized peripheral nerve allografts: An in vivo preclinical study in the rat sciatic nerve injury model

Nerve autograft is the gold standard technique to repair critical nerve defects, but efficient alternatives are needed. The present study evaluated the suitability of our novel Roosens‐based (RSN) decellularized peripheral nerve allografts (DPNAs) in the repair of 10‐mm sciatic nerve defect in rats at the functional and histological levels after 12 weeks. These DPNAs were compared with the autograft technique (AUTO) and Sondell (SD) or Hudson (HD) based DPNAs. Clinical and functional assessments demonstrated a partial regeneration in all operated animals. RSN‐based DPNAs results were comparable with SD and HD groups and closely comparable with the AUTO group without significant differences (p > .05). Overall hematological studies confirmed the biocompatibility of grafted DPNAs. In addition, biochemistry revealed some signs of muscle affection in all operated animals. These results were confirmed by the loss of weight and volume of the muscle and by muscle histology, especially in DPNAs. Histology of repaired nerves confirmed an active nerve tissue regeneration and partial myelination along with the implanted grafts, being the results obtained with HD and RSN‐based DPNAs comparable with the AUTO group. Finally, this in vivo study suggests that our novel RSN‐based DPNAs supported a comparable tissue regeneration, along the 10‐mm nerve gap, after 12‐week follow‐up to HD DPNAs, and both were superior to SD group and closely comparable with autograft technique. However, further improvements are needed to overcome the efficacy of the nerve autograft technique.     

Enhanced in vivo survival of Schwann cells by a synthetic oxygen carrier promotes sciatic nerve regeneration and functional recovery

Local hypoxia in the early stages of peripheral nerve injury is a challenge for axonal regeneration. To address this issue, perfluorotributylamine (PFTBA)‐based oxygen carrying fibrin hydrogel was prepared and injected into Schwann cell (SC)‐seeded collagen‐chitosan conduits to increase oxygen supply to SCs within the conduits. The conduit containing PFTBA‐SC gel was then applied to bridge a 15‐mm sciatic nerve defect in rats. It was observed that most of the GFP‐labeled SCs initially seeded in the PFTBA hydrogel remained alive for approximately 28 days after their in vivo implantation. The number of SCs was significantly higher in the PFTBA‐SC scaffold than that in the SC scaffold without PFTBA. In addition, nerve regeneration and functional recovery were examined after nerve injury repair. We found that the PFTBA‐SC scaffold was capable of promoting axonal regeneration and remyelination of the regenerated axons. Further studies showed the PFTBA‐SC scaffold was able to accelerate the recovery of motor and sensory function of the regenerating nerves. Electrophysiological analysis showed area under the curve of compound muscle action potential and nerve conduction velocity were also improved, and gastrocnemius muscle atrophy was partially reversed by PFTBA‐SC scaffold. Furthermore, microvessel density analysis showed PFTBA‐SC composites were beneficial for microvascular growth, which provided sustained oxygen for regenerating nerve in the later stages of nerve regeneration. In conclusion, enhanced survival of SCs by PFTBA is capable of promoting sciatic nerve regeneration and functional recovery, which provides a new avenue for achieving better functional recovery in the treatment of peripheral nerve injuries. Copyright © 2016 John Wiley & Sons, Ltd.     

Testosterone propionate can promote effects of acellular nerve allograft‐seeded bone marrow mesenchymal stem cells on repairing canine sciatic nerve

Peripheral human nerves fail to regenerate across long tube implants (>2 cm), and tissue‐engineered nerve grafts represent a promising treatment alternative. The present study aims to investigate the testosterone propionate (TP) repair effect of acellular nerve allograft (ANA) seeded with allogeneic bone marrow mesenchymal stem cells (BMSCs) on 3‐cm canine sciatic nerve defect. ANA cellularized with allogeneic BMSCs was implanted to the defect, and TP was injected into the lateral crus of the defected leg. The normal group, the autograft group, the ANA + BMSCs group, the ANA group, and the nongrafted group were used as control. Five months postoperatively, dogs in the TP + ANA + BMSCs group were capable of load bearing, normal walking, and skipping, the autograft group and the ANA + BMSCs group demonstrated nearly the same despite a slight limp. The compound muscle action potentials (CMAPs) on the injured side to the uninjured site in the TP + ANA + BMSCs group were significantly higher than that in the ANA + BMSCs group [CMAPs ratio at A: F(3, 20) = 191.40; 0.02, CMAPs ratio at B: F(3, 20) = 43.27; 0.01]. Masson trichrome staining revealed that in the TP + ANA + BMSCs group, both the diameter ratio of the myelinated nerve and the thickness ratio of regenerated myelin sheath were significantly larger than that in the other groups [the diameter of myelinated nerve fibers: F(3, 56) = 13.45; P < .01, the thickness ratio of regenerated myelin sheath: F(3, 56) = 51.25; P < .01]. In conclusion, TP could significantly increase the repairing effects of the ANA + BMSCs group, and their combination was able to repair 3‐cm canine sciatic nerve defect. It therefore represents a promising therapeutic approach.     

The advances in nerve tissue engineering: From fabrication of nerve conduit to in vivo nerve regeneration assays

Peripheral nerve damage is a common clinical complication of traumatic injury occurring after accident, tumorous outgrowth, or surgical side effects. Although the new methods and biomaterials have been improved recently, regeneration of peripheral nerve gaps is still a challenge. These injuries affect the quality of life of the patients negatively. In the recent years, many efforts have been made to develop innovative nerve tissue engineering approaches aiming to improve peripheral nerve treatment following nerve injuries. Herein, we will not only outline what we know about the peripheral nerve regeneration but also offer our insight regarding the types of nerve conduits, their fabrication process, and factors associated with conduits as well as types of animal and nerve models for evaluating conduit function. Finally, nerve regeneration in a rat sciatic nerve injury model by nerve conduits has been considered, and the main aspects that may affect the preclinical outcome have been discussed.     

股神经+坐骨+股外侧皮神经阻滞在膝关节骨性关节炎关节镜术中的作用分析

目的 探讨股神经+坐骨+股外侧皮神经阻滞在膝关节骨性关节炎(KOA)关节镜术中的作用。方法 选取2019年5月-2021年10月该院收治的拟行膝关节镜术治疗的KOA患者86例,依据随机数表法分为观察组和对照组,每组43例。对照组行连续硬膜外麻醉,观察组行股神经+坐骨+股外侧皮神经阻滞麻醉。比较两组患者的运动和感觉阻滞起效时间及持续时间,记录并比较两组患者的麻醉效果、麻醉前(T0)、麻醉后5 min (T₁)、手术10 min (T₂)、手术30 min (T₃)和手术结束时(T₄)的心率(HR)、平均动脉压(MAP)和不良反应总发生率。结果 观察组运动和感觉神经阻滞起效时间较对照组短(P <0.05),运动和感觉神经阻滞维持时间较对照组长(P <0.05);两组患者HR和MAP在组间、时间和交互方面比较,差异均有统计学意义(P <0.05);对照组的HR在T0时点与T1时点、T1时点与T3时点比较,差异均有统计学意义(P <0.05),MAP在T0时点与T1、T2、T3和T4...     

Laminin‐modified and aligned poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)/polyethylene oxide nanofibrous nerve conduits promote peripheral nerve regeneration

Poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) has received much attention for its biodegradability and biocompatibility, characteristics that are required in tissue engineering. In this study, polyethylene oxide (PEO)‐incorporated PHBV nanofibres with random or aligned orientation were obtained by electrospinning. For further use in vivo, the nanofibre films were made into nerve conduits after treatment with NH₃ plasma, which could improve the hydrophilicity of inner surfaces of nerve conduits and then facilitate laminin adsorption via electrostatic interaction for promoting cell adhesion and proliferation. Morphology of the surfaces of modified PHBV/PEO nanofibrous scaffolds were examined by scanning electron microscopy. Schwann cell viability assay was conducted and the results confirmed that the functionalized nanofibres were favourable for cell growth. Morphology of Schwann cells cultured on scaffolds showed that aligned nanofibrous scaffolds provided topographical guidance for cell orientation and elongation. Furthermore, three‐dimensional PHBV/PEO nerve conduits made from aligned and random‐oriented nanofibres were implanted into 12‐mm transected sciatic nerve rat model and subsequent analysis were conducted at 1 and 2 months postsurgery. The above functionalized PHBV/PEO scaffolds provide a novel and promising platform for peripheral nerve regeneration. Copyright © 2016 John Wiley & Sons, Ltd.     

合成材料神经导管与自体神经移植修复周围神经缺损的比较

背景：生物可降解材料制成的神经导管可在体内降解,避免出现的神经卡压等问题,因而受到越来越多的关注. 目的：比较自体神经移植与3种合成可生物降解材料神经导管在修复周围神经损伤的效果差异. 方法：通过电生理学检测,形态学观察等神经恢复效果评价方法,对比分析近年来常用的胶原神经导管、DL-乳酸-ε-己内酯神经导管、聚乙醇酸神经导管与自体神经移植修复周围神经缺损的效果. 结果与结论：虽然神经导管与自体神经移植相比在理论上有其优势的一面,但不同合成材料的神经导管之间在神经功能恢复中存在明显差异性,DL-乳酸-ε-己内酯神经导管修复效果与自体神经移植无明显差异,是较为理想的神经导管材料,聚乙醇酸神经导管因自身的因素影响其降解性能,在3种神经导管中的修复周围神经损伤效果最差,胶原神经导管需要交联剂改善其机械性能,其修复周围神经损伤效果居于前两者之间,因此,这3种神经导管在神经功能再生方面还有潜在的缺陷,不能完全替代自体神经移植,而且3者之间的性价比,还缺少足够的大样本长期随机对照实验结果来验证,还需要进一步的实验观察.     

In vitro evaluation of gel‐encapsulated adipose derived stem cells: Biochemical cues for in vivo peripheral nerve repair

Adipose‐derived stem cells (ASC) are becoming one of the most exploited cells in peripheral nerve repair. They are fast‐growing and able to protect neurons from apoptosis; they can reduce post‐injury latency and the risk of muscle atrophy. This study evaluates laminin‐loaded fibrin gel as an ASC‐carrying scaffold for nerve repair. In vitro, ASC retained their proliferative activity but showed significant increase in proliferation rate when encapsulated in gels with low laminin concentrations (i.e., 1 μg/mL). We observed a linear decrease of ASC proliferation rate with increasing laminin concentration from 1 to 100 μg/mL. We next examined the effect of the ASC‐carrying fibrin gels on in vitro dorsal root ganglia (DRG) neurite extension, then in vivo sciatic nerve regeneration in adult rats. The ASC‐carrying gel was embedded in 15‐mm‐long, 1.5‐mm‐diameter polydimethylsiloxane regenerative conduits for in vivo evaluation. At 8‐week post implantation, robust regeneration was observed across the long gap. Taken together, these results suggest ASC‐carrying gels are a potential path to improve the efficacy of nerve regeneration through artificial guidance conduits and electrode nerve interfaces.     

Undifferentiated and differentiated adipose‐derived stem cells improve nerve regeneration in a rat model of facial nerve defect

Autologous nerve grafting is the current procedure used for repairing facial nerve gaps. As an alternative to this method, tissue engineering cell‐based therapy using induced pluripotent stem cells, Schwann cells and bone marrow‐derived mesenchymal stem cells has been proposed. However, these cells have major problems, including tumorigenesis in induced pluripotent stem cells and invasiveness and limited tissue associated with harvesting for the other cells. Here, we investigated the therapeutic potential of adipose‐derived stem cells (ASCs), which can be harvested easily and repeatedly by a minimally invasive liposuction procedure. The ASCs had characteristics of mesenchymal tissue lineages and could differentiate into Schwann‐like cells that were relatively simple to isolate and expand in culture. In an in vivo study, a silicone conduit containing undifferentiated ASCs, differentiated ASCs or Schwann cells were transplanted, embedded in a collagen gel and the efficacy of repair of a 7 mm‐gap in the rat facial nerve examined. Morphometric quantification analysis of regenerated facial nerves after a regeneration period of 13 weeks showed that undifferentiated ASCs, differentiated ASCs, and Schwann cells had similar potential for nerve regeneration. Furthermore, the functional recovery of facial nerve regeneration using a rat facial palsy scoring system in the three groups was close to that in autologous nerve graft positive controls. These findings suggest that undifferentiated and differentiated ASCs may both have therapeutic potential in facial nerve regeneration as a source of Schwann cells in cell‐based therapy performed as an alternative to autologous nerve grafts. Copyright © 2014 John Wiley & Sons, Ltd.     

组织工程化神经导管修复外周神经损伤

背景：神经导管技术理论上采用生物或非生物材料预制成合适的管状支架,桥接神经断端两侧,在提供神经再生微环境的同时通过神经诱导、营养作用促进神经再生.目的：观察组织工程化神经导管修复外周神经损伤的临床效果.方法：选择24例陈旧性上肢神经损伤患者,以患者自愿原则分2组治疗：试验组采用组织工程化神经导管修复,对照组采用自体周围体表感觉神经移植修复.治疗后随访6个月观察患者肢体神经损伤功能修复效果.结果与结论：随访6个月后,两组肢体远端感觉运动功能与目测类比疼痛评分均较治疗前改善（P 〈0.05）,且试验组效果更好（P 〈0.05）;两组损伤侧感觉与运动神经传导速度均较治疗前改善（P 〈0.05）,且两组间差异无显著性意义.说明组织工程化神经导管材料符合神经修复导管支架的要求,临床应用疗效肯定.     

Functional collagen conduits combined with human mesenchymal stem cells promote regeneration after sciatic nerve transection in dogs

Numerous studies have focused on the development of novel and innovative approaches for the treatment of peripheral nerve injury using artificial nerve guide conduits. In this study, we attempted to bridge 3.5‐cm defects of the sciatic nerve with a longitudinally oriented collagen conduit (LOCC) loaded with human umbilical cord mesenchymal stem cells (hUC‐MSCs). The LOCC contains a bundle of longitudinally aligned collagenous fibres enclosed in a hollow collagen tube. Our previous studies showed that an LOCC combined with neurotrophic factors enhances peripheral nerve regeneration. However, it remained unknown whether an LOCC seeded with hUC‐MSCs could also promote regeneration. In this study, using various histological and electrophysiological analyses, we found that an LOCC provides mechanical support to newly growing nerves and functions as a structural scaffold for cells, thereby stimulating sciatic nerve regeneration. The LOCC and hUC‐MSCs synergistically promoted regeneration and improved the functional recovery in a dog model of sciatic nerve injury. Therefore, the combined use of an LOCC and hUC‐MSCs might have therapeutic potential for the treatment of peripheral nerve injury.     

A polylactic acid non‐woven nerve conduit for facial nerve regeneration in rats

This study developed a biodegradable nerve conduit with PLA non‐woven fabric and evaluated its nerve regeneration‐promoting effect. The buccal branch of the facial nerve of 8 week‐old Lewis rats was exposed, and a 7 mm nerve defect was created. A nerve conduit made of either PLA non‐woven fabric (mean fibre diameter 460 nm), or silicone tube filled with type I collagen gel, or an autologous nerve, was implanted into the nerve defect, and their nerve regenerative abilities were evaluated 13 weeks after the surgery. The number of myelinated neural fibres in the middle portion of the regenerated nerve was the highest for PLA tubes (mean ± SD, 5051 ± 2335), followed by autologous nerves (4233 ± 590) and silicone tubes (1604 ± 148). Axon diameter was significantly greater in the PLA tube group (5.17 ± 1.69 µm) than in the silicone tube group (4.25 ± 1.60 µm) and no significant difference was found between the PLA tube and autograft (5.53 ± 1.93 µm) groups. Myelin thickness was greatest for the autograft group (0.65 ± 0.24 µm), followed by the PLA tube (0.54 ± 0.18 µm) and silicone tube (0.38 ± 0.12 µm) groups, showing significant differences among the three groups. The PLA non‐woven fabric tube, composed of randomly‐connected PLA fibres, is porous and has a number of advantages, such as sufficient strength to maintain luminal structure. The tube has demonstrated a comparable ability to induce peripheral nerve regeneration following autologous nerve transplantation. Copyright © 2012 John Wiley & Sons, Ltd.     

Regenerative effects of human embryonic stem cell‐derived neural crest cells for treatment of peripheral nerve injury

Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential component of artificial grafts is biodegradable conduits and transplanted cells that provide trophic support during the regenerative process. Neural crest cells are promising support cell candidates because they are the parent population to many peripheral nervous system lineages. In this study, neural crest cells were differentiated from human embryonic stem cells. The differentiated cells exhibited typical stellate morphology and protein expression signatures that were comparable with native neural crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up‐regulation of several regeneration‐related genes was observed within the dorsal root ganglion and spinal cord segments harvested from transplanted animals. Our results demonstrate that the differentiated neural crest cells are biologically active and provide trophic support to stimulate peripheral nerve regeneration. Differentiated neural crest cells are therefore promising supporting cell candidates to aid in peripheral nerve repair.     

Decellularized nerve matrix hydrogel and glial‐derived neurotrophic factor modifications assisted nerve repair with decellularized nerve matrix scaffolds

Nerve defects are challenging to address clinically without satisfactory treatments. As a reliable alternative to autografts, decellularized nerve matrix scaffolds (DNM‐S) have been widely used in clinics for surgical nerve repair. However, DNM‐S remain inferior to autografts in their ability to support nerve regeneration for long nerve defects. In this study, we systematically and clearly presented the nano‐architecture of nerve‐specific structures, including the endoneurium, basement membrane and perineurium/epineurium in DNM‐S. Furthermore, we modified the DNM‐S by supplementing decellularized nerve matrix hydrogel (DNMG) and glial‐derived neurotrophic factor (GDNF) and then bridged a 50‐mm sciatic nerve defect in a beagle model. Fifteen beagles were randomly divided into three groups (five per group): an autograft group, DNM‐S group and GDNF‐DNMG‐modified DNM‐S (DNM‐S/GDNF@DNMG) group. DNM‐S/GDNF@DNMG, as optimized nerve grafts, were used to bridge nerve defects in the same manner as in the DNM‐S group. The repair outcome was evaluated by behavioural observations, electrophysiological assessments, regenerated nerve tissue histology and reinnervated target muscle examinations. Compared with the DNM‐S group, limb function, electrophysiological responses and histological findings were improved in the DNM‐S/GDNF@DNMG group 6 months after grafting, reflecting a narrower gap between the effects of DNM‐S and autografts. In conclusion, modification of DNM‐S with DNMG and GDNF enhanced nerve regeneration and functional recovery, indicating that noncellular modification of DNM‐S is a promising method for treating long nerve defects.     

Electrospun silk fibroin‐based neural scaffold for bridging a long sciatic nerve gap in dogs

Silk fibroin (SF)‐derived silkworms represent a type of highly biocompatible biomaterial for tissue engineering. We have previously investigated biocompatibility of SF with neural cells isolated from the central nervous system or peripheral nerve system in vitro, and also developed a SF‐based nerve graft conduit or tissue‐engineered nerve grafts by introducing bone marrow mesenchymal stem cells, as support cells, into SF‐based scaffold and evaluated the outcomes of peripheral nerve repair in a rat model. As an extension of the previous study, the electrospun technique was performed here to fabricate SF‐based neural scaffold inserted with silk fibres for bridging a 30‐mm‐long sciatic nerve gap in dogs. Assessments including functional, histological and morphometrical analyses were applied 12 months after surgery. All the results indicated that the SF‐based neural scaffold group achieved satisfactory regenerative outcomes, which were close to those achieved by autologous nerve grafts as the golden‐standard for peripheral nerve repair. Overall, our results raise a potential possibility for the translation of SF‐based electrospun neural scaffolds as an alternative to nerve autografts into the clinic.     

HRP神经逆行示踪评价GDNF修饰的神经移植复合体对大鼠脊髓运动神经元的保护作用

目的：采用大鼠坐骨神经缺损桥接动物模型,应用霍乱毒素B-辣根过氧化物酶（CB-HRP）神经逆行示踪技术对构建的GDNF修饰的神经移植复合体的运动神经元保护作用进行评价.方法：20只成年Wistar大鼠随机分为4组：A组（n=5）细胞外基质凝胶-PLGA管桥接组;B组（n=5）雪旺细胞-细胞外基质凝胶-PLGA管桥接组;C组（n=5）GDNF基因修饰的雪旺细胞-细胞外基质凝胶-PLGA管桥接组;D组（n=5）自体神经桥接组.损伤各组12周时应用辣根过氧化物酶神经逆行示踪技术进行脊髓前角运动神经元的再生评价.结果：12周时脊髓前角运动神经元再生评价结果提示：C组优于A、B组,而与D组相比差异无显著性意义.结论：雪旺细胞的转基因处理可能弥补单纯细胞移植神经营养因子含量的不足,而可能达到与自体神经移植相似的效果.