Approaches for Neural Tissue Regeneration

There is currently no treatment for neurodegenerative diseases such as Parkinson’s or Alzheimer’s diseases. While spinal cord injury has no treatment either, nerve injuries are being treated with autologous grafts, a procedure that in turn translates into a loss of function in the donor area. The development of therapies for these pathologies has become urgent as population keeps on ageing. A promising direction of investigation is the use of regenerative techniques to re-grow healthy and functional tissue in the injured area. In this review article, various approaches currently investigated to promote neural regeneration are covered. Those include approaches based on (and many times combining) stem cell therapy, scaffolds made of hydrogel, electrospun fibers and conductive materials as well as the use of soluble or non-diffusible growth factors.

[1]  Lei Lu,et al.  Electrical Stimulation to Conductive Scaffold Promotes Axonal Regeneration and Remyelination in a Rat Model of Large Nerve Defect , 2012, PloS one.

[2]  H. Kim,et al.  Effects of phosphate glass fiber-collagen scaffolds on functional recovery of completely transected rat spinal cords. , 2012, Acta biomaterialia.

[3]  Casey K. Chan,et al.  Enhancement of neurite outgrowth using nano-structured scaffolds coupled with laminin. , 2008, Biomaterials.

[4]  J. Deleo,et al.  Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain. , 1998, Brain research. Molecular brain research.

[5]  Lin Yu,et al.  Injectable hydrogels as unique biomedical materials. , 2008, Chemical Society reviews.

[6]  Chongli Zhong,et al.  Modeling of Drug Release from Bioerodible Polymer Matrices , 2005, Drug delivery.

[7]  J. Pawitan Prospect of cell therapy for Parkinson's disease , 2011, Anatomy & cell biology.

[8]  Yen Wei,et al.  Electrospinning polyaniline-contained gelatin nanofibers for tissue engineering applications. , 2006, Biomaterials.

[9]  C. Case,et al.  Extracellular matrix produced by bone marrow stromal cells and by their derivative, SB623 cells, supports neural cell growth , 2009, Journal of neuroscience research.

[10]  K. Conant,et al.  Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves , 2004, Experimental Neurology.

[11]  R. Kane,et al.  The effect of long-term release of Shh from implanted biodegradable microspheres on recovery from spinal cord injury in mice. , 2012, Biomaterials.

[12]  Tzu-Wei Wang,et al.  Carbon nanotube rope with electrical stimulation promotes the differentiation and maturity of neural stem cells. , 2012, Small.

[13]  M. Soleimani,et al.  Neural differentiation of mouse embryonic stem cells on conductive nanofiber scaffolds , 2012, Biotechnology Letters.

[14]  F. Cui,et al.  Combination of Hyaluronic Acid Hydrogel Scaffold and PLGA Microspheres for Supporting Survival of Neural Stem Cells , 2011, Pharmaceutical Research.

[15]  H. Kazemi,et al.  In Vitro Differentiation of Bone Marrow Stromal Cells into Oligodendrocyte-like Cells Using Triiodothyronine as Inducer , 2012, The International journal of neuroscience.

[16]  J. Altman,et al.  Development of the diencephalon in the rat. IV. Quantitative study of the time of origin of neurons and the internuclear chronological gradients in the thalamus , 1979, The Journal of comparative neurology.

[17]  Zhen Liu,et al.  Neuregulin-1β regulates outgrowth of neurites and migration of neurofilament 200 neurons from dorsal root ganglial explants in vitro , 2011, Peptides.

[18]  Xuesi Chen,et al.  Co-electrospun blends of PLGA, gelatin, and elastin as potential nonthrombogenic scaffolds for vascular tissue engineering. , 2011, Biomacromolecules.

[19]  M. May,et al.  Hypoglossal-Facial Nerve Interpositional-Jump Graft for Facial Reanimation without Tongue Atrophy , 1991, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[20]  E. Alleva,et al.  Psychiatric vulnerability: Suggestions from animal models and role of neurotrophins , 2009, Neuroscience & Biobehavioral Reviews.

[21]  Jong-Ho Lee,et al.  Recombinant human nerve growth factor (rhNGF-β) gene transfer promotes regeneration of crush-injured mental nerve in rats. , 2012, Oral surgery, oral medicine, oral pathology and oral radiology.

[22]  L. P. Tan,et al.  Cyclic tensile loading regulates human mesenchymal stem cell differentiation into neuron‐like phenotype , 2012, Journal of tissue engineering and regenerative medicine.

[23]  Erin B. Lavik,et al.  Using Polymer Chemistry to Modulate the Delivery of Neurotrophic Factors from Degradable Microspheres: Delivery of BDNF , 2009, Pharmaceutical Research.

[24]  Spinal Cord Injury Facts and Figures at a Glance , 2014, The journal of spinal cord medicine.

[25]  Yong Chen,et al.  Incorporating protein gradient into electrospun nanofibers as scaffolds for tissue engineering. , 2010, ACS applied materials & interfaces.

[26]  S. Hao,et al.  Co-transplantation of neural stem cells and Schwann cells within poly (L-lactic-co-glycolic acid) scaffolds facilitates axonal regeneration in hemisected rat spinal cord. , 2013, Chinese medical journal.

[27]  X. Mo,et al.  Preparation and characterization of coaxial electrospun thermoplastic polyurethane/collagen compound nanofibers for tissue engineering applications. , 2010, Colloids and surfaces. B, Biointerfaces.

[28]  Bin Wang,et al.  Novel nerve guidance material prepared from bovine aponeurosis. , 2006, Journal of biomedical materials research. Part A.

[29]  J. Shumsky,et al.  Treatments for , 2004 .

[30]  W. Freed,et al.  Dopaminergic Differentiation of Human Embryonic Stem Cells , 2004, Stem cells.

[31]  E. Feldman,et al.  IGF-I prevents glutamate-induced motor neuron programmed cell death , 2004, Neurobiology of Disease.

[32]  T. Gordon,et al.  Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo , 2003, Experimental Neurology.

[33]  Bai-Shuan Liu,et al.  Neural regeneration in a novel nerve conduit across a large gap of the transected sciatic nerve in rats with low-level laser phototherapy. , 2013, Journal of biomedical materials research. Part A.

[34]  Li Yao,et al.  Orienting neurite growth in electrospun fibrous neural conduits. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[35]  A. Khademhosseini,et al.  Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology , 2006 .

[36]  K. Beyreuther,et al.  Amyloid precursor protein regulates differentiation of human neural stem cells. , 2006, Stem cells and development.

[37]  J. Rubenstein,et al.  FGF and Shh Signals Control Dopaminergic and Serotonergic Cell Fate in the Anterior Neural Plate , 1998, Cell.

[38]  J. Jansen,et al.  Coaxially electrospun scaffolds based on hydroxyl-functionalized poly(ε-caprolactone) and loaded with VEGF for tissue engineering applications. , 2012, Biomacromolecules.

[39]  Nam-Hyung Kim,et al.  Exogenous Nurr1 gene expression in electrically-stimulated human MSCs and the induction of neurogenesis. , 2012, Biomaterials.

[40]  Cindi M Morshead,et al.  Hydrogel delivery of erythropoietin to the brain for endogenous stem cell stimulation after stroke injury. , 2012, Biomaterials.

[41]  Ling Huang,et al.  Chick embryonic Schwann cells migrate anodally in small electrical fields , 2008, Experimental Neurology.

[42]  David C. Martin,et al.  The design of electrospun PLLA nanofiber scaffolds compatible with serum-free growth of primary motor and sensory neurons. , 2008, Acta biomaterialia.

[43]  R. Linhardt,et al.  Preparation and characterization of electrospun core sheath nanofibers from multi-walled carbon nanotubes and poly(vinyl pyrrolidone). , 2012, Journal of nanoscience and nanotechnology.

[44]  H. Kim,et al.  Nanofibrous matrices of poly(lactic acid) and gelatin polymeric blends for the improvement of cellular responses. , 2008, Journal of biomedical materials research. Part A.

[45]  C. Morash,et al.  Nerve growth factor modulation of the cavernous nerve response to injury. , 2009, The journal of sexual medicine.

[46]  S. Tzeng,et al.  Photopolymerizable nanoarray hydrogels deliver CNTF and promote differentiation of neural stem cells , 2010 .

[47]  Mario Grassi,et al.  Mathematical modelling and controlled drug delivery: matrix systems. , 2005, Current drug delivery.

[48]  O. Hermanson,et al.  Recombinant spider silk matrices for neural stem cell cultures. , 2012, Biomaterials.

[49]  Gary E. Wnek,et al.  TAILORING TISSUE ENGINEERING SCAFFOLDS USING ELECTROSTATIC PROCESSING TECHNIQUES: A STUDY OF POLY(GLYCOLIC ACID) ELECTROSPINNING , 2001 .

[50]  R. Gilbert,et al.  Fabrication and characterization of tunable polysaccharide hydrogel blends for neural repair. , 2011, Acta biomaterialia.

[51]  J. de Vellis,et al.  Prevention of gliotic scar formation by NeuroGel™ allows partial endogenous repair of transected cat spinal cord , 2004, Journal of neuroscience research.

[52]  Young-tae Kim,et al.  In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury. , 2006, Biomaterials.

[53]  S. Ramakrishna,et al.  Electrospun polyethersulfone affinity membrane: membrane preparation and performance evaluation. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[54]  Steven G Potkin,et al.  A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease , 2005, Nature Medicine.

[55]  W. Saltzman,et al.  Impact of cell type and density on nerve growth factor distribution and bioactivity in 3-dimensional collagen gel cultures. , 2006, Tissue engineering.

[56]  M. Courtois,et al.  Prenatal development of mouse central nervous structures: time of neuron origin and gradients of neuronal production. A radioautographic study. , 1982, Journal fur Hirnforschung.

[57]  Santiago Costantino,et al.  Patterning protein concentration using laser-assisted adsorption by photobleaching, LAPAP. , 2008, Lab on a chip.

[58]  Y. S. Kim,et al.  Generation of dopaminergic neurons in vitro from human embryonic stem cells treated with neurotrophic factors , 2004, Neuroscience Letters.

[59]  Xiao-dan Jiang,et al.  Combination of bone marrow stromal cell transplantation with mobilization by granulocyte-colony stimulating factor promotes functional recovery after spinal cord transection , 2009, Acta Neurochirurgica.

[60]  Federica Chiellini,et al.  Poly(lactic-co-glycolic acid) electrospun fibrous meshes for the controlled release of retinoic acid. , 2010, Acta biomaterialia.

[61]  C. Svendsen,et al.  In vitro localization of human neural stem cell neurogenesis by engineered FGF-2 gradients. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[62]  F. Guillemot,et al.  Neurogenin1 and neurogenin2 control two distinct waves of neurogenesis in developing dorsal root ganglia. , 1999, Genes & development.

[63]  A. Álvarez-Buylla,et al.  Glial Nature of Adult Neural Stem Cells: Neurogenic Competence in Adult Astrocytes , 2012 .

[64]  Lisa N Gillespie,et al.  BDNF‐induced survival of auditory neurons in vivo: Cessation of treatment leads to accelerated loss of survival effects , 2003, Journal of neuroscience research.

[65]  W. Mark Saltzman,et al.  Distribution of nerve growth factor following direct delivery to brain interstitium , 1995, Brain Research.

[66]  Mingwu Shen,et al.  Electrospun hybrid nanofibers doped with nanoparticles or nanotubes for biomedical applications. , 2012, Therapeutic delivery.

[67]  C. Schmidt,et al.  Nerve Growth Factor-Immobilized Electrically Conducting Fibrous Scaffolds for Potential Use in Neural Engineering Applications , 2012, IEEE Transactions on NanoBioscience.

[68]  M. Mattson,et al.  Neural progenitor cells grown on hydrogel surfaces respond to the product of the transgene of encapsulated genetically engineered fibroblasts. , 2010, Biomacromolecules.

[69]  David J. Anderson,et al.  Mash1 and neurogenin1 Expression Patterns Define Complementary Domains of Neuroepithelium in the Developing CNS and Are Correlated with Regions Expressing Notch Ligands , 1997, The Journal of Neuroscience.

[70]  M. Mozafari,et al.  Synthesis and characterization of electrospun polyvinyl alcohol nanofibrous scaffolds modified by blending with chitosan for neural tissue engineering , 2012, International journal of nanomedicine.

[71]  Reid L Skeel,et al.  Genetically engineered mesenchymal stem cells reduce behavioral deficits in the YAC 128 mouse model of Huntington's disease , 2010, Behavioural Brain Research.

[72]  Robert H Miller The promise of stem cells for neural repair , 2006, Brain Research.

[73]  K. Sugaya,et al.  How to approach Alzheimer's disease therapy using stem cell technologies. , 2008, Journal of Alzheimer's disease : JAD.

[74]  Seeram Ramakrishna,et al.  An Introduction to Electrospinning and Nanofibers (Paperback) , 2005 .

[75]  B. Song,et al.  Sustained local delivery of bioactive nerve growth factor in the central nervous system via tunable diblock copolypeptide hydrogel depots. , 2012, Biomaterials.

[76]  Michael J McShane,et al.  Fabrication of interdigitated micropatterns of self-assembled polymer nanofilms containing cell-adhesive materials. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[77]  J. Takahashi,et al.  Matrigel supports survival and neuronal differentiation of grafted embryonic stem cell‐derived neural precursor cells , 2009, Journal of neuroscience research.

[78]  D. Moran,et al.  Conductive Core–Sheath Nanofibers and Their Potential Application in Neural Tissue Engineering , 2009, Advanced functional materials.

[79]  O. Hermanson,et al.  Inkjet printing of macromolecules on hydrogels to steer neural stem cell differentiation. , 2007, Biomaterials.

[80]  Tao Xu,et al.  Viability and electrophysiology of neural cell structures generated by the inkjet printing method. , 2006, Biomaterials.

[81]  J. Winter,et al.  Hydrogel-electrospun fiber composite materials for hydrophilic protein release. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[82]  Shih-Hao Huang,et al.  Selective Deposition of Electrospun Alginate-Based Nanofibers onto Cell-Repelling Hydrogel Surfaces for Cell-Based Microarrays , 2011 .

[83]  JaneR . Taylor,et al.  The behavioral and biochemical effects of BDNF containing polymers implanted in the hippocampus of rats , 2010, Brain Research.

[84]  Younan Xia,et al.  Radially aligned, electrospun nanofibers as dural substitutes for wound closure and tissue regeneration applications. , 2010, ACS nano.

[85]  P. Caroni,et al.  Nerve sprouting in innervated adult skeletal muscle induced by exposure to elevated levels of insulin-like growth factors , 1990, The Journal of cell biology.

[86]  George Collins,et al.  Neurite extension of primary neurons on electrospun piezoelectric scaffolds. , 2011, Acta biomaterialia.

[87]  G. Forloni,et al.  Multiple drug delivery hydrogel system for spinal cord injury repair strategies. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[88]  Nobuko Uchida,et al.  Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[89]  Balaji Narasimhan,et al.  Mathematical modeling of polymer erosion: consequences for drug delivery. , 2011, International journal of pharmaceutics.

[90]  A L Dellon,et al.  An Alternative to the Classical Nerve Graft for the Management of the Short Nerve Gap , 1988, Plastic and reconstructive surgery.

[91]  Ravi S Kane,et al.  The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells. , 2009, Biomaterials.

[92]  Nadine Kabbani,et al.  Enhanced Proliferation, Survival, and Dopaminergic Differentiation of CNS Precursors in Lowered Oxygen , 2000, The Journal of Neuroscience.

[93]  H. Iwata,et al.  Improvement of neural stem cell survival in collagen hydrogels by incorporating laminin-derived cell adhesive polypeptides. , 2012, Bioconjugate chemistry.

[94]  Ji Suk Choi,et al.  Nerve growth factor (NGF)-conjugated electrospun nanostructures with topographical cues for neuronal differentiation of mesenchymal stem cells. , 2010, Acta biomaterialia.

[95]  O. Steward,et al.  Salmon fibrin treatment of spinal cord injury promotes functional recovery and density of serotonergic innervation , 2012, Experimental Neurology.

[96]  M A Vandelli,et al.  Potential use of polymeric nanoparticles for drug delivery across the blood-brain barrier. , 2013, Current medicinal chemistry.

[97]  Alain Finkel,et al.  World Scientific Publishing Company , 2013 .

[98]  J. Qin,et al.  Porous chitosan scaffold and ngf promote neuronal differentiation of neural stem cells in vitro. , 2011, Neuro endocrinology letters.

[99]  A. Martinez,et al.  Insulin-like growth factor-I mediates neuroprotection in proteasome inhibition-induced cytotoxicity in SH-SY5Y cells , 2011, Molecular and Cellular Neuroscience.

[100]  Hans P Merkle,et al.  Hydrogel nerve conduits produced from alginate/chitosan complexes. , 2007, Journal of biomedical materials research. Part A.

[101]  A. Zechariah,et al.  Intracerebroventricularly delivered VEGF promotes contralesional corticorubral plasticity after focal cerebral ischemia via mechanisms involving anti-inflammatory actions , 2012, Neurobiology of Disease.

[102]  Renata V Weber,et al.  Processed nerve allografts for peripheral nerve reconstruction: A multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions , 2012, Microsurgery.

[103]  Ravi V Bellamkonda,et al.  Differences between the effect of anisotropic and isotropic laminin and nerve growth factor presenting scaffolds on nerve regeneration across long peripheral nerve gaps. , 2008, Biomaterials.

[104]  E. Entcheva,et al.  Electrospun fine-textured scaffolds for heart tissue constructs. , 2005, Biomaterials.

[105]  F. Qi,et al.  A synthetic oxygen carrier in fibrin matrices promotes sciatic nerve regeneration in rats. , 2013, Acta biomaterialia.

[106]  H. Kim,et al.  Biofunctionalized carbon nanotubes in neural regeneration: a mini-review. , 2013, Nanoscale.

[107]  P. Wood,et al.  Fabrication of growth factor- and extracellular matrix-loaded, gelatin-based scaffolds and their biocompatibility with Schwann cells and dorsal root ganglia. , 2012, Biomaterials.

[108]  Z. Karabekian,et al.  Stem Cell Rev and Rep , 2010 .

[109]  Lucel Sirghi,et al.  Micro-stamped surfaces for the patterned growth of neural stem cells. , 2008, Biomaterials.

[110]  Alabama,et al.  Spinal Cord Injury Facts and Figures at a Glance , 2013, The journal of spinal cord medicine.

[111]  A. Di Carlo Human and economic burden of stroke. , 2009, Age and ageing.

[112]  Jae Young Lee,et al.  Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications. , 2009, Biomaterials.

[113]  Cindi M Morshead,et al.  Controlled epi-cortical delivery of epidermal growth factor for the stimulation of endogenous neural stem cell proliferation in stroke-injured brain. , 2011, Biomaterials.

[114]  Hui Zhao,et al.  The use of laminin modified linear ordered collagen scaffolds loaded with laminin-binding ciliary neurotrophic factor for sciatic nerve regeneration in rats. , 2011, Biomaterials.

[115]  C. Hegg,et al.  ATP differentially upregulates fibroblast growth factor 2 and transforming growth factor alpha in neonatal and adult mice: effect on neuroproliferation , 2011, Neuroscience.

[116]  Hongkui Wang,et al.  Repairing rat sciatic nerve injury by a nerve‐growth‐factor‐loaded, chitosan‐based nerve conduit , 2012, Biotechnology and applied biochemistry.

[117]  S. Y. Chew,et al.  Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair. , 2012, Journal of biomedical materials research. Part A.

[118]  Dominique Zosso,et al.  Synergistic NGF/B27 Gradients Position Synapses Heterogeneously in 3D Micropatterned Neural Cultures , 2011, PloS one.

[119]  L. Vargova,et al.  Heterogeneous PHPMA hydrogels for tissue repair and axonal regeneration in the injured spinal cord. , 1998, Journal of biomaterials science. Polymer edition.

[120]  Christophe Vieu,et al.  Engineering of adult human neural stem cells differentiation through surface micropatterning. , 2012, Biomaterials.

[121]  H. Bysell,et al.  Recombinant spider silk as matrices for cell culture. , 2010, Biomaterials.

[122]  Y. Seo,et al.  Stimulation of sub-sonic vibration promotes the differentiation of adipose tissue-derived mesenchymal stem cells into neural cells. , 2012, Life sciences.

[123]  Daniel J. Macaya,et al.  Injectable hydrogel materials for spinal cord regeneration: a review. , 2012, Biomedical materials.

[124]  Malcolm K Horne,et al.  Three-dimensional nanofibrous scaffolds incorporating immobilized BDNF promote proliferation and differentiation of cortical neural stem cells. , 2010, Stem cells and development.

[125]  John G. Flanagan,et al.  Development of Continuous and Discrete Neural Maps , 2007, Neuron.

[126]  Mauro Grigioni,et al.  Structural characterization and cell response evaluation of electrospun PCL membranes: micrometric versus submicrometric fibers. , 2009, Journal of biomedical materials research. Part A.

[127]  Hongjun Song,et al.  The influence of fiber diameter of electrospun substrates on neural stem cell differentiation and proliferation. , 2009, Biomaterials.

[128]  Zhifeng Xiao,et al.  Linear ordered collagen scaffolds loaded with collagen-binding brain-derived neurotrophic factor improve the recovery of spinal cord injury in rats. , 2009, Tissue engineering. Part A.

[129]  S. Thanos,et al.  Intravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo , 1993, Brain Research.

[130]  Tae Gwan Park,et al.  Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery. , 2009, Advanced drug delivery reviews.

[131]  H. Iwata,et al.  Enhanced proliferation of neural stem cells in a collagen hydrogel incorporating engineered epidermal growth factor. , 2011, Biomaterials.

[132]  Darrell H. Reneker,et al.  Electrospinning process and applications of electrospun fibers , 1993, Conference Record of the 1993 IEEE Industry Applications Conference Twenty-Eighth IAS Annual Meeting.

[133]  Heungsoo Shin,et al.  Development of electroactive and elastic nanofibers that contain polyaniline and poly(L-lactide-co-epsilon-caprolactone) for the control of cell adhesion. , 2008, Macromolecular bioscience.

[134]  Tzu-Wei Wang,et al.  Micropatterned stretching system for the investigation of mechanical tension on neural stem cells behavior. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[135]  Heungsoo Shin,et al.  Nanofibrous poly(lactic acid)/hydroxyapatite composite scaffolds for guided tissue regeneration. , 2008, Macromolecular bioscience.

[136]  R. Shi,et al.  Rapidly photo-cross-linkable chitosan hydrogel for peripheral neurosurgeries. , 2011, Biomacromolecules.

[137]  J. Montastruc Treatment of Parkinson's disease should begin with a dopamine agonist , 2000, Movement disorders : official journal of the Movement Disorder Society.

[138]  Uma Maheswari Krishnan,et al.  Fabrication of uniaxially aligned 3D electrospun scaffolds for neural regeneration , 2011, Biomedical materials.

[139]  S. Wiegand,et al.  BDNF and NT-4/5 Prevent Atrophy of Rat Rubrospinal Neurons after Cervical Axotomy, Stimulate GAP-43 and Tα1-Tubulin mRNA Expression, and Promote Axonal Regeneration , 1997, The Journal of Neuroscience.

[140]  Cindi M Morshead,et al.  A hydrogel composite system for sustained epi-cortical delivery of Cyclosporin A to the brain for treatment of stroke. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[141]  X. Mo,et al.  The Effect of Aligned Core–Shell Nanofibres Delivering NGF on the Promotion of Sciatic Nerve Regeneration , 2012, Journal of biomaterials science. Polymer edition.

[142]  J. Trojanowski,et al.  Transplantation of Cryopreserved Human Embryonal Carcinoma-Derived Neurons (NT2N Cells) Promotes Functional Recovery in Ischemic Rats , 1998, Experimental Neurology.

[143]  T. Gordon,et al.  Transforming growth factor‐β and forskolin attenuate the adverse effects of long‐term Schwann cell denervation on peripheral nerve regeneration in vivo , 2002, Glia.

[144]  Feng Zhang,et al.  The effects of electrospun TSF nanofiber diameter and alignment on neuronal differentiation of human embryonic stem cells. , 2012, Journal of biomedical materials research. Part A.

[145]  P. Ferruti,et al.  Biological performance of a novel biodegradable polyamidoamine hydrogel as guide for peripheral nerve regeneration. , 2011, Journal of biomedical materials research. Part A.

[146]  J. Nolta,et al.  Mesenchymal stem cells for the treatment of neurodegenerative disease. , 2010, Regenerative medicine.

[147]  W. Mark Saltzman,et al.  Intracranial Delivery of Recombinant Nerve Growth Factor: Release Kinetics and Protein Distribution for Three Delivery Systems , 1999, Pharmaceutical Research.

[148]  E. Kobatake,et al.  The promotion of angiogenesis by growth factors integrated with ECM proteins through coiled-coil structures. , 2013, Biomaterials.

[149]  M. Vemuri,et al.  Neural Development and Stem Cells , 2012, Stem Cell Biology and Regenerative Medicine.

[150]  T. Ben-Hur,et al.  Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. , 2008, Archives of neurology.

[151]  Malcolm K Horne,et al.  Neurite infiltration and cellular response to electrospun polycaprolactone scaffolds implanted into the brain. , 2009, Biomaterials.

[152]  R. Gorga,et al.  Fabrication and characterization of electrospun chitosan nanofibers formed via templating with polyethylene oxide. , 2008, Biomacromolecules.

[153]  J. Cole,et al.  Investigation of Polyurea-Crosslinked Silica Aerogels as a Neuronal Scaffold: A Pilot Study , 2012, PloS one.

[154]  M. Kreutzer,et al.  Highly Malignant Behavior of a Murine Oligodendrocyte Precursor Cell Line following Transplantation into the Demyelinated and Nondemyelinated Central Nervous System , 2012, Cell transplantation.

[155]  K. Sun,et al.  Nerve regeneration following spinal cord injury using matrix metalloproteinase-sensitive, hyaluronic acid-based biomimetic hydrogel scaffold containing brain-derived neurotrophic factor. , 2009, Journal of biomedical materials research. Part A.

[156]  Jessica O. Winter,et al.  Hydrogel–Electrospun Fiber Mat Composite Coatings for Neural Prostheses , 2011, Front. Neuroeng..

[157]  S. Akbareian,et al.  Gdnf is mitogenic, neurotrophic, and chemoattractive to enteric neural crest cells in the embryonic colon , 2011, Developmental dynamics : an official publication of the American Association of Anatomists.

[158]  F. Gage,et al.  IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes , 2004, The Journal of cell biology.