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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

Two-dimensional Effects of Hydrogel Self-organized from IKVAV-containing Peptides on Growth and Differentiation of NSCs

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Journal of Wuhan University of Technology(Materials Science) 2009年第2期24卷 186-192页

作者：宋玉林 Department of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and Technology

The neural stem cells （NSCs） were seeded in the surface layer of hydrogels made of IKVAV-containing peptide amphiphile. Two-dimensional effects of hydrogel on growth and differentiation of NSCs were investigated. Peptide was synthesized in solid way. Cells were harvested from the cerebral cortex of neonatal mice, identified by immunohistochemical methods. Cells were incubated in the surface layer of self-assembled peptide hydrogel and coverslips for seven days respectively,detected immunocytochemically for NF and GFAP. The molecular weight （Mw） of Peptide was 1438 and purity was 95.22%. Cells were identified as Nestin-positive NSCs. TEM showed that hydrogel was composed of interactive nanofibers. NSCs extended processes, and were able to be dif- ferentiated into NF-positive neurons with red fluorescence and GFAP-positive astrocytes with green one in the surface of hydrogel. However, NSCs only formed undifferentiated neurospheres in the surface layer of coverslips. Results indicate that the self-assembled hydrogel from peptide amphiphile has good cyto-compatibility to NSCs and induced their differentiation.

关键词： nerve tissue engineering hydrogel self-assembly neural stem cells

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 *** 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 ***,this research was aimed to fabricate heparin/growth factors(GFs)-immobilized artificial *** was covalently immobilized onto aligned electrospun polycapro-lactone/gelatin(PCL/Gel)***,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 *** 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 *** permeability of bovine serum albumin(BSA)from nanofibrous membranes was further assessed and found to be comparable with the commercialized cel-lulose acetate *** 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 *** in vivo evaluation revealed the accumulation of host cells into the transplanted *** 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

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 *** under hypoxia is considered to enhance the release of the regenerative potential of *** 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 ***,histologic evaluation showed significantly increased axon outgrowth/branching,axon density,remyelination,and a reduced relative connective tissue *** pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve *** 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

Strategies for regeneration of components of nervous system: scaffolds, cells and biomolecules

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Regenerative Biomaterials 2015年第1期2卷 31-45页

作者： Lingling Tian Molamma P.Prabhakaran Seeram Ramakrishna Mechanical engineering Faculty of EngineeringNational University of Singapore2 Engineering Drive 3Singapore 117576 Nanoscience and Nanotechnology Initiative National University of Singapore2 Engineering Drive 3Singapore 117576

nerve diseases including acute injury such as peripheral nerve injury(PNI),spinal cord injury(SCI)and traumatic brain injury(TBI),and chronic disease like neurodegeneration disease can cause various function disorders of nervous system,such as those relating to memory and voluntary *** nerve diseases produce great burden for individual families and the society,for which a lot of efforts have been *** pathways represent a unidirectional and aligned architecture allowing systematic axonal development within the *** a traumatic injury,the intricate architecture suffers disruption leading to inhibition of growth and loss of *** to limited capacity of the body to regenerate axonal pathways,it is desirable to have biomimetic approach that has the capacity to graft a bridge across the lesion while providing optimal mechanical and biochemical cues for tissue *** for central nervous system injury,one more extra precondition is compulsory:creating a less inhibitory surrounding for axonal *** is a cost-effective and straightforward technique to fabricate extracellular matrix(ECM)-like nanofibrous structures,with various fibrous forms such as random fibers,aligned fibers,3D fibrous scaffold and core-shell fibers from a variety of *** diversity and versatility of electrospinning technique,together with functionalizing cues such as neurotrophins,ECM-based proteins and conductive polymers,have gained considerable success for the nerve tissue *** are convinced that in the future the stem cell therapy with the support of functionalized electrospun nerve scaffolds could be a promising therapy to cure nerve diseases.

关键词： electrospinning nerve tissue engineering nanofibers functionalized scaffolds

Fabrication and Characterization of Dual-layer Multichannel nerve Guidance Conduit

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Journal of Donghua University(English Edition) 2017年第1期34卷 167-170页

作者：孙彬彬吴桐王娟布托阿齐袁柳李丹丹莫秀梅 Biomaterials and tissue engineering Laboratory College of Chemistry Chemical Engineering & Bioengineering Donghua University Shanghai 201620 China

Nowadays, muifichannel nerve guidance conduit （NGC） was designed by mimicking the architecture of nerve fascicles, and it was used to reduce dispersion of regenerating axons within the NGC lumen. In this paper, gelatin was used to prepare multichannel inner layer of NGC by freeze-drying, and poly （ L-lactic add-co-ε- caprolactone）（P（LLA-CL）） was used to fabricate nanofiber outer layer of NGC by electrospinning. The morphology of dual-layer mtlltichannel NGC was observed by scanning electron microscopy （SEM）. In vitro degradation experiment of the NGC demonstrated that the inner layer of NGC had the faster degradation rate than the outer layer of NGC. tell viability assay indicated that Schwann cells （SCs） showed better proliferation on dual-layer multichannel NGC than hollow NGC, because the multichannel structure introduced contact guidance for direct cell migration. Therefore, it was suggested that the dual-layer multichannel NGC had the potential for nerve lissue regeneration.

关键词： poly(L-lactic acid-co-ε-caprolactone) (P(LLA-CL)) gelatin electrospinniag multichannel nerve tissue engineering

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 ***,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 *** this work,we provide a state-of-the-art review of the latest development of 3D printing for bioengineered neural *** 3D printing techniques for neural tissue-engineered scaffolds or living cell-laden constructs are summarized and compared in terms of their unique *** 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 *** 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 *** 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

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

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

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