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Neural Regeneration Research 2016年第10期11卷 1644-1652页

作者： Jun-feng Zhou Yi-guo Wang Liang Cheng Zhao Wu Xiao-dan Sun Jiang Peng Key Laboratory of Advanced Materials of Ministry of Education of China School of Materials Science and Engineering Tsinghua UniversityBeijing China Institute of Orthopedics Chinese PLA General Hospital Beijing China School of Medicine Nankai University Tianjin China The Neural Regeneration Co-innovation Center of Jiangsu Province Nantong Jiangsu Province China

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.

关键词： nerve regeneration polypyrrole electrospinning conductivity electrical property Schwann cells human umbilical cord mesenchymalstem cells nerve tissue engineering nanofibrous scaffolds neural regeneration

3D printing of functional bioengineered constructs for neural regeneration: a review

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International Journal of Extreme Manufacturing 2023年第4期5卷 87-118页

作者： Hui Zhu Cong Yao Boyuan Wei Chenyu Xu Xinxin Huang Yan Liu Jiankang He Jianning Zhang Dichen Li State Key Laboratory for Manufacturing Systems engineering Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China Department of Neurosurgery The First Medical CenterChinese PLA General HospitalBeijing 100853People’s Republic of China

Three-dimensional(3D)printing technology has opened a new paradigm to controllably and reproducibly fabricate bioengineered neural constructs for potential applications in repairing injured nervous tissues or producing in vitro nervous tissue models.However,the complexity of nervous tissues poses great challenges to 3D-printed bioengineered analogues,which should possess diverse architectural/chemical/electrical functionalities to resemble the native growth microenvironments for functional neural regeneration.In this work,we provide a state-of-the-art review of the latest development of 3D printing for bioengineered neural constructs.Various 3D printing techniques for neural tissue-engineered scaffolds or living cell-laden constructs are summarized and compared in terms of their unique advantages.We highlight the advanced strategies by integrating topographical,biochemical and electroactive cues inside 3D-printed neural constructs to replicate in vivo-like microenvironment for functional neural regeneration.The typical applications of 3D-printed bioengineered constructs for in vivo repair of injured nervous tissues,bio-electronics interfacing with native nervous system,neural-on-chips as well as brain-like tissue models are demonstrated.The challenges and future outlook associated with 3D printing for functional neural constructs in various categories are discussed.

关键词： 3D printing bioengineered neural constructs neural regeneration nerve tissue engineering nervous tissue models

Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model

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Neural Regeneration Research 2023年第3期18卷 652-656页

作者： Julius M.Mayer Christian Krug Maximilian M.Saller Annette Feuchtinger Riccardo E.Giunta Elias Volkmer Thomas Holzbach Department of Hand-and Plastic Surgery Spital ThurgauFrauenfeldSwitzerland Musculoskeletal University Center Munich(MUM) Department of Orthopedics and Trauma SurgeryLudwig-Maximilians-University(LMU)Planegg-MartinsriedGermany Research Unit Analytical Pathology MunichHelmholtz Zentrum München-German Research Center for Environmental Health(GmbH)NeuherbergGermany Division of Hand- Plastic-and Aesthetic SurgeryLudwig-Maximilians-University(LMU)MunichGermany Division of Hand Surgery Helios Klinikum München WestMunichGermany

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.

关键词： adipose-derived progenitor cells adipose-derived multipotent stem/progenitor cell autologous nerve graft fibrin conduit hypoxia hypoxic pre-conditioning nerve defect nerve tissue engineering peripheral nerve regeneration regenerative medicine

Heparin/Growth Factors‑Immobilized Aligned Electrospun Nanofibers Promote nerve Regeneration in Polycaprolactone/Gelatin‑Based nerve Guidance Conduits

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Advanced Fiber Materials 2023年第2期5卷 554-573页

作者： Yasuhiro Ikegami Muhammad Shafiq Shinichi Aishima Hiroyuki Ijima Department of Chemical engineering Faculty of EngineeringGraduate SchoolKyushu University744 MotookaNishi‑KuFukuoka 819‑0395Japan Department of Biotechnology Faculty of Science and TechnologyUniversity of Central Punjab(UCP)Lahore 54000Pakistan Department of Pathology and Microbiology Faculty of MedicineSaga UniversityNabeshima 5‑1‑1Saga 849‑8501Japan

Injuries to the nervous system account for the widespread morbidity,mortality,and discomfort worldwide.Artificial nerve guidance conduits(NGCs)offer a promising platform for nerve reconstruction,however,they require extracellular matrix(ECM)-like features to better mimic the in vivo microenvironment.Consequently,this research was aimed to fabricate heparin/growth factors(GFs)-immobilized artificial NGCs.Heparin was covalently immobilized onto aligned electrospun polycapro-lactone/gelatin(PCL/Gel)nanofibers.Thereafter,basic fibroblast growth factor(bFGF)and nerve growth factor(NGF)were preferentially immobilized on heparinized nanofibers;the immobilization efficiency of GFs was found to be 50%with respect to(w.r.t.)their initial loaded amounts.The in vivo implantation of NGCs in a sciatic nerve defect model revealed the successful retention(~10%w.r.t the initial loaded amount)and bioactivity of NGF for up to 5 days.The permeability of bovine serum albumin(BSA)from nanofibrous membranes was further assessed and found to be comparable with the commercialized cel-lulose acetate membranes.The bioactivity of NGCs was assessed in a sciatic nerve defect model in rats for short-term(1 week)and long-term(1-month).The NGCs displayed good structural stability and biocompatibility in vivo.The in vivo evaluation revealed the accumulation of host cells into the transplanted NGCs.Taken together;these heparin/GFs-immobilized artificial NGCs may have broad implications for nerve regeneration and related tissue engineering disciplines.

关键词： Heparin Growth factor-immobilized scaffolds Aligned nanofibers Core/shell nanofibers nerve tissue engineering Scaffolds Co-axial electrospinning

Electrospun silk fibroin nanofibers promote Schwann cell adhesion, growth and proliferation

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Neural Regeneration Research 2012年第15期7卷 1171-1178页

作者： Aijun Hu Baoqi Zuo Feng Zhang Qing Lan Huanxiang Zhang Department of Otolaryngy the Second Affiliated Hospital of Soochow University Suzhou 215021 Jiangsu Province China College of Textiles and Clothing engineering Soochow University Suzhou 215021 Jiangsu Province China National engineering Laboratory for Modern Silk Suzhou 215023 Jiangsu Province China Jiangsu Province Key Laboratory of Stem Cell Research Medical College of Soochow University Suzhou 215007 Jiangsu Province China Department of Neurology the Second Affiliated Hospital of Soochow University Suzhou 215004 Jiangsu Province China

In this study, Schwann cells, at a density of 1 x 105 cells/well, were cultured on regenerated silk fibroin nanofibers （305 ＋ 84 nm） prepared using the electrospinning method. Schwann cells cultured on the silk fibroin nanofibers appeared more ordered, their processes extended further, and they formed more extensive and complex interconnections. In addition, the silk fibroin nanofibers had no impact on the proliferation of Schwann cells or on the secretion of ciliary neurotrophic factor, brain-derived neurotrophic factor or nerve growth factor. These findings indicate that regenerated electrospun silk fibroin nanofibers can promote Schwann cell adhesion, growth and proliferation, and have excellent biocompatibility.

关键词： peripheral nerve regeneration nerve tissue engineering Schwann cells silk fibroin electrospinning neural regeneration

Biocompatibility evaluation of electrospun aligned poly(propylene carbonate) nanofibrous scaffolds with peripheral nerve tissues and cells in vitro

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Chinese Medical Journal 2011年第15期124卷 2361-2366页

作者： WANG Yu ZHAO Zhe ZHAO Binx ZHAO Bin QI Hong-xu PENG Jiang ZHANG Li XU Wen-jing HU Ping LU Shi-bi Orthopedics Research Institute of Chinese People＇s Liberation Army Chinese People＇s Liberation Army General Hospital Beijing 100853 China Institute of Polymer Science and Technology Tsinghua University Beijing 100084 China

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 we

关键词： dorsal root ganglia electrospinning nerve tissue engineering poly（propylene carbonate） Schwann cell

Combining acellular nerve allografts with brainderived neurotrophic factor transfected bone marrow mesenchymal stem cells restores sciatic nerve injury better than either intervention alone

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Neural Regeneration Research 2014年第20期9卷 1814-1819页

作者： Yanru Zhang Hui Zhang Gechen Zhang Ka Ka Wenhua Huang School of International Education Zhengzhou University Institute of Clinical Anatomy Southern Medical University Department of Orthopedic Surgery First Affiliated Hospital of Zhengzhou University

In this study, we chemically extracted acellular nerve allografts from bilateral sciatic nerves, and repaired 10-mm sciatic nerve defects in rats using these grafts and brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells. Experiments were performed in three groups： the acellular nerve allograft bridging group, acellular nerve allograft ＋ bone marrow mesenchymal stem cells group, and the acellular nerve allograft ＋ brain-derived neurotrophic factor transfected bone marrow mesenchyrnal stem cells group. Results showed that at 8 weeks after bridging, sciatic functional index, triceps wet weight recovery rate, myelin thickness, and number of myelinated nerve fibers were significantly changed in the three groups. Variations were the largest in the acellular nerve allograft ＋ brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells group compared with the other two groups. Experimental findings suggest that chemically extracted acellular nerve allograft combined nerve factor and mesenchymal stem cells can promote the restoration of sciatic nerve defects. The repair effect seen is better than the single application of acellular nerve allograft or acellular nerve allograft combined mesenchymal stem cell transplantation.

关键词： nerve regeneration peripheral nerve regeneration peripheral nerve injury chemicallyextracted acellular nerve brain-derived neurotrophic factor bone marrow mesenchymal stem cells nerve tissue engineering neural regeneration

Comparison of viscoelasticity between normal human sciatic nerve and amniotic membrane

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Neural Regeneration Research 2013年第14期8卷 1269-1275页

作者： Donghui Xu Conghai Zhao Huili Ma Jun Wei Dongyuan Li Department of Neurosurgery China-Japan Union HospitalJilin University Department of Road & Bridge College of TransportationJilin University

Sciatic nerve tissue was obtained from the gluteus maximus muscle segment of normal human cadavers and amniotic membrane tissue was obtained from healthy human puerperant placentas. Both tissues were analyzed for their stress relaxation and creep properties to determine suitability for transplantation applications. Human amniotic membrane and sciatic nerve tissues had similar tendencies for stress relaxation and creep properties. The stress value of the amniotic membrane stress relaxation group decreased to a greater extent compared with the sciatic nerve stress relaxation group. Similarly, the stress value of the amniotic membrane creep group increased to a greater extent compared with the sciatic nerve creep group. The stress relaxation curve for human amniotic membrane and sciatic nerve showed a logarithm correlation, while the creep curve showed an exponential correlation. These data indicate that amniotic membrane tissue has better stress relaxation and creep properties compared with sciatic nerve tissue.

关键词： neural regeneration basic research cadaver human sciatic nerve amniotic membrane stressrelaxation creep viscoelasticity stress biomechanics nerve tissue engineering neuroregeneration

Platelet-rich plasma gel in combination with Schwann cells for repair of sciatic nerve injury

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Neural Regeneration Research 2012年第29期7卷 2286-2292页

作者： Fagang Ye Haiyan Li Guangxi Qiao Feng Chen Hao Tao Aiyu Ji Yanling Hu Department of Trauma Surgery Affiliated Hospital of Medical College Qingdao University Qingdao 266000 Shandong Province China

Bone marrow mesenchymal stem cells were isolated from New Zealand white rabbits, culture-expanded and differentiated into Schwann cell-like cells. Autologous platelet-dch plasma and Schwann cell-like cells were mixed in suspension at a density of 1 x 106 cells/mL, prior to introduction into a poly （lactic-co-glycolic acid） conduit. Fabricated tissue-engineered nerves were implanted into rabbits to bridge 10 mm sciatic nerve defects （platelet-rich plasma group）. Controls were established using fibrin as the seeding matrix for Schwann cell-like cells at identical density to construct tissue-engineered nerves （fibrin group）. Twelve weeks after implantation, toluidine blue staining and scanning electron microscopy were used to demonstrate an increase in the number of regenerating nerve fibers and thickness of the myelin sheath in the platelet-rich plasma group compared with the fibrin group. Fluoro-gold retrograde labeling revealed that the number of Fluoro-gold-positive neurons in the dorsal root ganglion and the spinal cord anterior horn was greater in the platelet-rich plasma group than in the fibrin group. Electrophysiological examination confirmed that compound muscle action potential and nerve conduction velocity were superior in the platelet-rich plasma group compared with the fibrin group. These results indicate that autologous platelet-rich plasma gel can effectively serve as a seeding matrix for Schwann cell-like cells to construct tissue-engineered nerves to promote perJpheral nerve regeneration.

关键词： platelet-rich plasma extracellular matrix Schwann cells fibrin sciatic nerve peripheral nerve injury nerve tissue engineering neural regeneration

Construction of a three-dimensional bionic nerve conduit containing two neurotrophic factors with separate delivery systems for the repair of sciatic nerve defects

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Neural Regeneration Research 2011年第13期6卷 988-994页

作者： Zhiyue Li Qun Zhao Ran Bi Yong Zhuang Siyin Feng Department of Orthopedics Third Xiangya Hospital Central South University Changsha 410013 Hunan Province China Department of Orthopedics Hunan Provincial People's Hospital Changsha 410013 Hunan Province China

Previous studies of nerve conduits have investigated numerous properties, such as conduit luminal structure and neurotrophic factor incorporation, for the regeneration of nerve defects. The present study used a poly（lactic-co-glycolic acid）（PLGA） copolymer to construct a three-dimensional （3D） bionic nerve conduit, with two channels and multiple microtubule lumens, and incorporating two neurotrophic factors, each with their own delivery system, as a novel environment for peripheral nerve regeneration. The efficacy of this conduit in repairing a 1.5 cm sciatic nerve defect was compared with PLGA-alone and PLGA-microfilament conduits, and autologous nerve transplantation. Results showed that compared with the other groups, the 3D bionic nerve conduit had the fastest nerve conduction velocity, largest electromyogram amplitude, and shortest electromyogram latency. In addition, the nerve fiber density, myelin sheath thickness and axon diameter were significantly increased, and the recovery rate of the triceps surae muscle wet weight was lowest. These findings suggest that 3D bionic nerve conduits can provide a suitable microenvironment for peripheral nerve regeneration to efficiently repair sciatic nerve defects. p

关键词： oly（lactic-co-glycolic acid） sciatic nerve defect nerve conduit bionics nerve tissue engineering neural regeneration