Scaffolds for central nervous system tissue engineering

Traumatic injuries to the brain and spinal cord of the central nervous system (CNS) lead to severe and permanent neurological deficits and to date there is no universally accepted treatment. Owing to the profound impact, extensive studies have been carried out aiming at reducing inflammatory responses and overcoming the inhibitory environment in the CNS after injury so as to enhance regeneration. Artificial scaffolds may provide a suitable environment for axonal regeneration and functional recovery, and are of particular importance in cases in which the injury has resulted in a cavitary defect. In this review we discuss development of scaffolds for CNS tissue engineering, focusing on mechanism of CNS injuries, various biomaterials that have been used in studies, and current strategies for designing and fabricating scaffolds.

[1]  Zhaoyang Yang,et al.  Repair of thoracic spinal cord injury by chitosan tube implantation in adult rats. , 2009, Biomaterials.

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

[3]  M. Shoichet,et al.  Biomaterials for neural-tissue engineering — Chitosan supports the survival, migration, and differentiation of adult-derived neural stem and progenitor cells , 2010 .

[4]  G. Y. Ozgenel Effects of hyaluronic acid on peripheral nerve scarring and regeneration in rats. , 2003, Microsurgery.

[5]  M. Přádný,et al.  Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 6: 3D hydrogels with positive and negative surface charges and polyelectrolyte complexes in spinal cord injury repair , 2009, Journal of materials science. Materials in medicine.

[6]  Nic D. Leipzig,et al.  The effect of substrate stiffness on adult neural stem cell behavior. , 2009, Biomaterials.

[7]  Huanxing Su,et al.  Reknitting the injured spinal cord by self-assembling peptide nanofiber scaffold. , 2007, Nanomedicine : nanotechnology, biology, and medicine.

[8]  S. Strittmatter,et al.  Localization of Nogo-A and Nogo-66 Receptor Proteins at Sites of Axon–Myelin and Synaptic Contact , 2002, The Journal of Neuroscience.

[9]  S. Strittmatter,et al.  Axon Regeneration in Young Adult Mice Lacking Nogo-A/B , 2003, Neuron.

[10]  J. Noth,et al.  Cytocompatibility of a novel, longitudinally microstructured collagen scaffold intended for nerve tissue repair. , 2009, Tissue engineering. Part A.

[11]  Seeram Ramakrishna,et al.  Mesenchymal stem cell differentiation to neuronal cells on electrospun nanofibrous substrates for nerve tissue engineering. , 2009, Biomaterials.

[12]  R. Mirsky,et al.  Schwann cells as regulators of nerve development , 2002, Journal of Physiology-Paris.

[13]  Tsukasa Akasaka,et al.  Effect of carbon nanotubes on cellular functions in vitro. , 2009, Journal of biomedical materials research. Part A.

[14]  J. Leroux,et al.  Novel injectable neutral solutions of chitosan form biodegradable gels in situ. , 2000, Biomaterials.

[15]  F. Cui,et al.  Hyaluronic acid hydrogel modified with nogo-66 receptor antibody and poly-L-lysine to promote axon regrowth after spinal cord injury. , 2010, Journal of biomedical materials research. Part B, Applied biomaterials.

[16]  Laura A. Smith,et al.  Nano-fibrous scaffolds for tissue engineering. , 2004, Colloids and surfaces. B, Biointerfaces.

[17]  J. L. Rodriguez,et al.  Consequences of high-dose steroid therapy for acute spinal cord injury. , 1997, The Journal of trauma.

[18]  G. Özgenel Effects of hyaluronic acid on peripheral nerve scarring and regeneration in rats , 2003 .

[19]  W Shain,et al.  Fabrication and optimization of alginate hydrogel constructs for use in 3D neural cell culture , 2011, Biomedical materials.

[20]  Guang-Zhen Jin,et al.  Neurite outgrowth of dorsal root ganglia neurons is enhanced on aligned nanofibrous biopolymer scaffold with carbon nanotube coating , 2011, Neuroscience Letters.

[21]  S. Campo,et al.  Molecular size hyaluronan differently modulates toll-like receptor-4 in LPS-induced inflammation in mouse chondrocytes. , 2010, Biochimie.

[22]  Miqin Zhang,et al.  Fabrication and cellular compatibility of aligned chitosan–PCL fibers for nerve tissue regeneration , 2011 .

[23]  N. Lee,et al.  Amine-modified single-walled carbon nanotubes protect neurons from injury in a rat stroke model. , 2011, Nature nanotechnology.

[24]  M. Wiberg,et al.  A novel use of alginate hydrogel as Schwann cell matrix. , 2001, Tissue engineering.

[25]  P. Tran,et al.  Carbon nanofibers and carbon nanotubes in regenerative medicine. , 2009, Advanced drug delivery reviews.

[26]  R. Shelton,et al.  Comparison of bone marrow cell growth on 2D and 3D alginate hydrogels , 2005, Journal of materials science. Materials in medicine.

[27]  B. Geiger,et al.  Environmental sensing through focal adhesions , 2009, Nature Reviews Molecular Cell Biology.

[28]  Wensheng Li,et al.  Electrospun nanofibers immobilized with collagen for neural stem cells culture , 2008, Journal of materials science. Materials in medicine.

[29]  Younan Xia,et al.  Neurite outgrowth on nanofiber scaffolds with different orders, structures, and surface properties. , 2009, ACS nano.

[30]  T. Okamoto,et al.  Akt-Mediated Survival of Oligodendrocytes Induced by Neuregulins , 2000, The Journal of Neuroscience.

[31]  J. Hubbell,et al.  Development of fibrin derivatives for controlled release of heparin-binding growth factors. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[32]  Jae Min Lim,et al.  The effect of the controlled release of nerve growth factor from collagen gel on the efficiency of neural cell culture. , 2009, Biomaterials.

[33]  M. Tuszynski,et al.  Guidance molecules in axon regeneration. , 2010, Cold Spring Harbor perspectives in biology.

[34]  M. Fehlings,et al.  Epidemiology, demographics, and pathophysiology of acute spinal cord injury. , 2001, Spine.

[35]  M. Chopp,et al.  Treatment of Traumatic Brain Injury in Adult Rats with Intravenous Administration of Human Bone Marrow Stromal Cells , 2001, Neurosurgery.

[36]  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.

[37]  Wei Zheng,et al.  The promotion of neural progenitor cells proliferation by aligned and randomly oriented collagen nanofibers through β1 integrin/MAPK signaling pathway. , 2011, Biomaterials.

[38]  A. Roskams,et al.  Olfactory ensheathing cells of the lamina propria in vivo and in vitro , 2003, Glia.

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

[40]  M. Longaker,et al.  Hyaluronate metabolism undergoes an ontogenic transition during fetal development: implications for scar-free wound healing. , 1993, Journal of pediatric surgery.

[41]  L. Mckerracher,et al.  Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth , 1994, Neuron.

[42]  Martin Möller,et al.  Human neural cell interactions with orientated electrospun nanofibers in vitro. , 2009, Nanomedicine.

[43]  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.

[44]  D. Schaffer,et al.  Scaffolds based on degradable alginate hydrogels and poly(lactide-co-glycolide) microspheres for stem cell culture. , 2007, Biomaterials.

[45]  M. Horne,et al.  Morphology and gelation of thermosensitive chitosan hydrogels. , 2005, Biophysical chemistry.

[46]  R Langer,et al.  Stimulation of neurite outgrowth using an electrically conducting polymer. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[47]  F. Cui,et al.  In vitro behavior of neural stem cells in response to different chemical functional groups. , 2009, Biomaterials.

[48]  R. Shi,et al.  Behavioral recovery from spinal cord injury following delayed application of polyethylene glycol. , 2002, The Journal of experimental biology.

[49]  C. Schmidt,et al.  Synthesis of a Novel, Biodegradable Electrically Conducting Polymer for Biomedical Applications , 2002 .

[50]  G. Ramakers,et al.  Depolarization stimulates lamellipodia formation and axonal but not dendritic branching in cultured rat cerebral cortex neurons. , 1998, Brain research. Developmental brain research.

[51]  Wei Wang,et al.  Effects of Schwann cell alignment along the oriented electrospun chitosan nanofibers on nerve regeneration. , 2009, Journal of biomedical materials research. Part A.

[52]  J. Fawcett,et al.  The glial scar and central nervous system repair , 1999, Brain Research Bulletin.

[53]  J. Mcdonald,et al.  Robust CNS regeneration after complete spinal cord transection using aligned poly-L-lactic acid microfibers. , 2011, Biomaterials.

[54]  R. Langer,et al.  An injectable, biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury , 2006, Experimental Neurology.

[55]  P Aebischer,et al.  Three-dimensional extracellular matrix engineering in the nervous system. , 1998, Journal of biomedical materials research.

[56]  Ying Luo,et al.  A photolabile hydrogel for guided three-dimensional cell growth and migration , 2004, Nature materials.

[57]  A. Sauaia,et al.  Epidemiology of trauma deaths: a reassessment. , 1993, The Journal of trauma.

[58]  M. Chopp,et al.  Delayed transplantation of human marrow stromal cell-seeded scaffolds increases transcallosal neural fiber length, angiogenesis, and hippocampal neuronal survival and improves functional outcome after traumatic brain injury in rats , 2009, Brain Research.

[59]  Karen L. Smith,et al.  Biohybrid Carbon Nanotube/Agarose Fibers for Neural Tissue Engineering , 2011, Advanced functional materials.

[60]  J. Verhaagen,et al.  Injury-Induced Class 3 Semaphorin Expression in the Rat Spinal Cord , 2002, Experimental Neurology.

[61]  D G Stein,et al.  Biocompatibility of methylcellulose-based constructs designed for intracerebral gelation following experimental traumatic brain injury. , 2001, Biomaterials.

[62]  David C. Martin,et al.  Effect of Immobilized Nerve Growth Factor on Conductive Polymers: Electrical Properties and Cellular Response , 2007 .

[63]  M. Filbin Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS , 2003, Nature Reviews Neuroscience.

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

[65]  B. Zuo,et al.  Guidance of Olfactory Ensheathing Cell Growth and Migration on Electrospun Silk Fibroin Scaffolds , 2010, Cell transplantation.

[66]  C H Tator,et al.  Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. , 1991, Journal of neurosurgery.

[67]  M. Hájek,et al.  HPMA-RGD hydrogels seeded with mesenchymal stem cells improve functional outcome in chronic spinal cord injury. , 2010, Stem cells and development.

[68]  Y. Takai,et al.  Hyaluronan-based Biomaterials in Tissue Engineering , 2004 .

[69]  M. Schwab,et al.  Patterns of Nogo mRNA and Protein Expression in the Developing and Adult Rat and After CNS Lesions , 2002, The Journal of Neuroscience.

[70]  Charles Tator,et al.  Matrix inclusion within synthetic hydrogel guidance channels improves specific supraspinal and local axonal regeneration after complete spinal cord transection. , 2006, Biomaterials.

[71]  X. Yu,et al.  Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain , 2007, Biomedical materials.

[72]  Charles Tator Update on the Pathophysiology and Pathology of Acute Spinal Cord Injury , 1995, Brain pathology.

[73]  C. Zhao,et al.  The enhancement of cell adherence and inducement of neurite outgrowth of dorsal root ganglia co-cultured with hyaluronic acid hydrogels modified with Nogo-66 receptor antagonist in vitro , 2006, Neuroscience.

[74]  Yasunori Hayashi,et al.  Entrapment of migrating hippocampal neural cells in three-dimensional peptide nanofiber scaffold. , 2004, Tissue engineering.

[75]  M. Mahoney,et al.  Effect of macromer weight percent on neural cell growth in 2D and 3D nondegradable PEG hydrogel culture. , 2010, Journal of biomedical materials research. Part A.

[76]  B. Barres,et al.  Multiple extracellular signals are required for long-term oligodendrocyte survival. , 1993, Development.

[77]  C. Werner,et al.  Self-assembled monolayers with different terminating groups as model substrates for cell adhesion studies. , 2004, Biomaterials.

[78]  J. Freeman,et al.  Electrical stimulation of nerve regeneration in the rat: The early effects evaluated by a vibrating probe and electron microscopy , 1991, Neuroscience.

[79]  Jeffrey A. Hubbell,et al.  Enzymatic incorporation of bioactive peptides into fibrin matrices enhances neurite extension , 2000, Nature Biotechnology.

[80]  A. Rich,et al.  Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[81]  Younan Xia,et al.  The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages. , 2009, Biomaterials.

[82]  W. Park,et al.  Blood compatibility and biodegradability of partially N-acylated chitosan derivatives. , 1995, Biomaterials.

[83]  Andrés J. García,et al.  Role of fibronectin in topographical guidance of neurite extension on electrospun fibers. , 2011, Biomaterials.

[84]  Lauren Flynn,et al.  Fiber templating of poly(2-hydroxyethyl methacrylate) for neural tissue engineering. , 2003, Biomaterials.

[85]  G. Fischbach,et al.  Axonal Neuregulin Signals Cells of the Oligodendrocyte Lineage through Activation of HER4 and Schwann Cells through HER2 and HER3 , 1997, The Journal of cell biology.

[86]  Eva L Feldman,et al.  Aligned electrospun nanofibers specify the direction of dorsal root ganglia neurite growth. , 2007, Journal of biomedical materials research. Part A.

[87]  R. Kotek,et al.  The promotion of axon extension in vitro using polymer-templated fibrin scaffolds. , 2011, Biomaterials.

[88]  C. Schmidt,et al.  Synthesis and characterization of polypyrrole-hyaluronic acid composite biomaterials for tissue engineering applications. , 2000, Journal of biomedical materials research.

[89]  D. K. Cullen,et al.  CNS injury biomechanics and experimental models. , 2007, Progress in brain research.

[90]  Mingyong Gao,et al.  Precision microchannel scaffolds for central and peripheral nervous system repair , 2011, Journal of materials science. Materials in medicine.

[91]  O. Steward,et al.  The Unique Histopathological Responses of the Injured Spinal Cord: Implications for Neuroprotective Therapy , 1999, Annals of the New York Academy of Sciences.

[92]  M. Zurita,et al.  Functional recovery in chronic paraplegia after bone marrow stromal cells transplantation , 2004, Neuroreport.

[93]  M. Ruitenberg,et al.  Expression of the Gene Encoding the Chemorepellent Semaphorin III Is Induced in the Fibroblast Component of Neural Scar Tissue Formed Following Injuries of Adult But Not Neonatal CNS , 1999, Molecular and Cellular Neuroscience.

[94]  Michael G. Fehlings,et al.  Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury , 2008, The Journal of Neuroscience.

[95]  Xiaodong Sun,et al.  Combinated Transplantation of Neural Stem Cells and Collagen Type I Promote Functional Recovery After Cerebral Ischemia in Rats , 2010, Anatomical record.

[96]  A. Fournier,et al.  Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor , 2002, Science.

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

[98]  Zhaoyang Yang,et al.  The effect of neurotrophin-3/chitosan carriers on the proliferation and differentiation of neural stem cells. , 2009, Biomaterials.

[99]  C. Schmidt,et al.  Electrical stimulation alters protein adsorption and nerve cell interactions with electrically conducting biomaterials. , 2001, Biomaterials.

[100]  J. Hunt,et al.  Controlling the phenotype and function of mesenchymal stem cells in vitro by adhesion to silane-modified clean glass surfaces. , 2005, Biomaterials.

[101]  Scott R. Whittemore,et al.  Pluripotent Stem Cells Engrafted into the Normal or Lesioned Adult Rat Spinal Cord Are Restricted to a Glial Lineage , 2001, Experimental Neurology.

[102]  S. Ramakrishna,et al.  Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. , 2005, Biomaterials.

[103]  Albert J. Keung,et al.  Substrate modulus directs neural stem cell behavior. , 2008, Biophysical journal.

[104]  Krista L. Niece,et al.  Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers , 2004, Science.

[105]  S. Sakiyama-Elbert,et al.  Controlled Release of Neurotrophin-3 and Platelet-Derived Growth Factor from Fibrin Scaffolds Containing Neural Progenitor Cells Enhances Survival and Differentiation into Neurons in a Subacute Model of SCI , 2010, Cell transplantation.

[106]  H. Markram,et al.  Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts. , 2009, Nature nanotechnology.

[107]  In-Yong Kim,et al.  Chitosan and its derivatives for tissue engineering applications. , 2008, Biotechnology advances.

[108]  S. Hollister,et al.  Macro-architectures in spinal cord scaffold implants influence regeneration. , 2008, Journal of neurotrauma.

[109]  Andrés J. García,et al.  Human mesenchymal stem cell differentiation on self-assembled monolayers presenting different surface chemistries. , 2010, Acta biomaterialia.

[110]  Alexander Star,et al.  Biodegradation of single-walled carbon nanotubes through enzymatic catalysis. , 2008, Nano letters.

[111]  DiAnna L. Hynds,et al.  Neurite Outgrowth Inhibition by Chondroitin Sulfate Proteoglycan: Stalling/Stopping Exceeds Turning in Human Neuroblastoma Growth Cones , 1999, Experimental Neurology.

[112]  Nicholas C. Spitzer,et al.  Electrical activity in early neuronal development , 2006, Nature.

[113]  J. Bresnahan,et al.  Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys , 1997, Nature Medicine.

[114]  Robert Langer,et al.  Stimulation of neurite outgrowth by neurotrophins delivered from degradable hydrogels. , 2006, Biomaterials.

[115]  Smadar Cohen,et al.  Liver tissue engineering within alginate scaffolds: effects of cell-seeding density on hepatocyte viability, morphology, and function. , 2003, Tissue engineering.

[116]  S. Y. Chew,et al.  Photochemical crosslinked electrospun collagen nanofibers: synthesis, characterization and neural stem cell interactions. , 2010, Journal of biomedical materials research. Part A.

[117]  The axonal regeneration across a honeycomb collagen sponge applied to the transected spinal cord. , 2008, Journal of medical and dental sciences.

[118]  Stacie A. Chvatal,et al.  Spatial distribution and acute anti-inflammatory effects of Methylprednisolone after sustained local delivery to the contused spinal cord. , 2008, Biomaterials.

[119]  M. Soleimani,et al.  The promotion of stemness and pluripotency following feeder-free culture of embryonic stem cells on collagen-grafted 3-dimensional nanofibrous scaffold. , 2011, Biomaterials.

[120]  M. Spector,et al.  An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model , 2007, Biomedical materials.

[121]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[122]  G. Schneider,et al.  Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[123]  M. Schwab,et al.  Systemic Deletion of the Myelin-Associated Outgrowth Inhibitor Nogo-A Improves Regenerative and Plastic Responses after Spinal Cord Injury , 2003, Neuron.

[124]  Zhigang He,et al.  Glial inhibition of CNS axon regeneration , 2006, Nature Reviews Neuroscience.

[125]  F. Cui,et al.  Preparation and characterization of fibroin/hyaluronic acid composite scaffold. , 2009, International journal of biological macromolecules.

[126]  S. Sakiyama-Elbert,et al.  Effect of controlled delivery of neurotrophin-3 from fibrin on spinal cord injury in a long term model. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[127]  P. Casaccia‐Bonnefil Cell death in the oligodendrocyte lineage: A molecular perspective of life/death decisions in development and disease , 2000, Glia.

[128]  Paul D. Dalton,et al.  Guidance of glial cell migration and axonal growth on electrospun nanofibers of poly-ε-caprolactone and a collagen/poly-ε-caprolactone blend , 2007 .

[129]  Xiaosong Gu,et al.  The interaction of Schwann cells with chitosan membranes and fibers in vitro. , 2004, Biomaterials.

[130]  R. Pallini,et al.  Acrylic hydrogel implants after spinal cord lesion in the adult rat , 2001, Neurological research.

[131]  Charles Tator,et al.  Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury , 2007, Bone Marrow Transplantation.

[132]  A. Harvey,et al.  Neural tissue formation within porous hydrogels implanted in brain and spinal cord lesions: ultrastructural, immunohistochemical, and diffusion studies. , 1999, Tissue engineering.

[133]  Marco Domeniconi,et al.  Myelin-Associated Glycoprotein Interacts with the Nogo66 Receptor to Inhibit Neurite Outgrowth , 2002, Neuron.

[134]  David F Meaney,et al.  Matrices with compliance comparable to that of brain tissue select neuronal over glial growth in mixed cortical cultures. , 2006, Biophysical journal.

[135]  Aqing Chen,et al.  Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord , 1997, Journal of neurocytology.

[136]  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.

[137]  H. Okano,et al.  Nerve Growth Factor Protects Oligodendrocytes from Tumor Necrosis Factor-α-induced Injury through Akt-mediated Signaling Mechanisms* , 2000, The Journal of Biological Chemistry.

[138]  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.

[139]  M. Sipski,et al.  High-dose methylprednisolone may cause myopathy in acute spinal cord injury patients , 2005, Spinal Cord.

[140]  Y. Tabata,et al.  Attachment, proliferation and adipogenic differentiation of adipo-stromal cells on self-assembled monolayers of different chemical compositions , 2008, Journal of biomaterials science. Polymer edition.

[141]  Yoshihisa Suzuki,et al.  Electrophysiological and horseradish peroxidase-tracing studies of nerve regeneration through alginate-filled gap in adult rat spinal cord , 2002, Neuroscience Letters.

[142]  Benjamin G Keselowsky,et al.  Surface chemistry modulates focal adhesion composition and signaling through changes in integrin binding. , 2004, Biomaterials.

[143]  Mário A Barbosa,et al.  Adhesion of human leukocytes to biomaterials: an in vitro study using alkanethiolate monolayers with different chemically functionalized surfaces. , 2003, Journal of biomedical materials research. Part A.

[144]  W. Tetzlaff,et al.  Peripheral olfactory ensheathing cells reduce scar and cavity formation and promote regeneration after spinal cord injury , 2004, The Journal of comparative neurology.

[145]  M. Horne,et al.  Inflammatory response on injection of chitosan/GP to the brain , 2006, Journal of materials science. Materials in medicine.

[146]  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.

[147]  Martin E. Schwab,et al.  Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1 , 2000, Nature.

[148]  Bingcang Li,et al.  PLGA conduit seeded with olfactory ensheathing cells for bridging sciatic nerve defect of rats. , 2010, Journal of biomedical materials research. Part A.

[149]  S. Ichinose,et al.  Hydroxyapatite-coated tendon chitosan tubes with adsorbed laminin peptides facilitate nerve regeneration in vivo , 2003, Brain Research.

[150]  S. Ichinose,et al.  Influences of mechanical properties and permeability on chitosan nano/microfiber mesh tubes as a scaffold for nerve regeneration. , 2008, Journal of biomedical materials research. Part A.

[151]  E. Rosenzweig,et al.  Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[152]  J. Silver,et al.  Robust Regeneration of Adult Sensory Axons in Degenerating White Matter of the Adult Rat Spinal Cord , 1999, The Journal of Neuroscience.

[153]  J. Kellerth,et al.  Survival effects of BDNF and NT‐3 on axotomized rubrospinal neurons depend on the temporal pattern of neurotrophin administration , 2000, The European journal of neuroscience.

[154]  X. Yu,et al.  Hyaluronic acid hydrogel as Nogo-66 receptor antibody delivery system for the repairing of injured rat brain: in vitro. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[155]  Judith Klein-Seetharaman,et al.  Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. , 2010, Nature nanotechnology.

[156]  Milica Radisic,et al.  Vascular endothelial growth factor immobilized in collagen scaffold promotes penetration and proliferation of endothelial cells. , 2008, Acta biomaterialia.

[157]  S. Tzeng,et al.  Sustained intraspinal delivery of neurotrophic factor encapsulated in biodegradable nanoparticles following contusive spinal cord injury. , 2008, Biomaterials.

[158]  M. Oudega,et al.  Neurotrophins Reduce Degeneration of Injured Ascending Sensory and Corticospinal Motor Axons in Adult Rat Spinal Cord , 2002, Experimental Neurology.

[159]  Michelle K. Leach,et al.  Accelerated neuritogenesis and maturation of primary spinal motor neurons in response to nanofibers , 2010, Developmental neurobiology.

[160]  Benjamin G. Keselowsky,et al.  Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[161]  M. Pipitone,et al.  Neurotrophic and migratory properties of an olfactory ensheathing cell line , 2001, Glia.

[162]  Zin Z. Khaing,et al.  High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury , 2011, Journal of neural engineering.

[163]  A. Dalton,et al.  Aligned, isotropic and patterned carbon nanotube substrates that control the growth and alignment of Chinese hamster ovary cells , 2011, Nanotechnology.

[164]  Jonas Baltrusaitis,et al.  The development of electrically conductive polycaprolactone fumarate-polypyrrole composite materials for nerve regeneration. , 2010, Biomaterials.

[165]  Timothy P. Lodge,et al.  Thermoreversible Gelation of Aqueous Methylcellulose Solutions , 1999 .

[166]  P. Zandstra,et al.  The use of vascular endothelial growth factor functionalized agarose to guide pluripotent stem cell aggregates toward blood progenitor cells. , 2010, Biomaterials.

[167]  M. Beattie,et al.  Cell death in models of spinal cord injury. , 2002, Progress in brain research.

[168]  Xiao-Ming Xu,et al.  Glial cell line-derived neurotrophic factor-enriched bridging transplants promote propriospinal axonal regeneration and enhance myelination after spinal cord injury , 2003, Experimental Neurology.

[169]  M. Přádný,et al.  Biocompatible hydrogels in spinal cord injury repair. , 2008, Physiological research.

[170]  R. Gilbert,et al.  Controlled release of 6-aminonicotinamide from aligned, electrospun fibers alters astrocyte metabolism and dorsal root ganglia neurite outgrowth , 2011, Journal of neural engineering.

[171]  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.

[172]  S. Davies,et al.  Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican V2, and tenascin‐C during acute to chronic maturation of spinal cord scar tissue , 2003, Journal of neuroscience research.

[173]  Fumio Nakamura,et al.  Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein , 2000, Nature.

[174]  A. Ulman,et al.  Formation and Structure of Self-Assembled Monolayers. , 1996, Chemical reviews.

[175]  M. Oudega,et al.  Schwann cell transplantation for repair of the adult spinal cord. , 2006, Journal of neurotrauma.

[176]  Q. Xu,et al.  Hyaluronic acid hydrogel immobilized with RGD peptides for brain tissue engineering , 2006, Journal of materials science. Materials in medicine.

[177]  Dustin J. Maxwell,et al.  Rationally designed peptides for controlled release of nerve growth factor from fibrin matrices. , 2007, Journal of biomedical materials research. Part A.

[178]  M. Chopp,et al.  COLLAGEN SCAFFOLDS POPULATED WITH HUMAN MARROW STROMAL CELLS REDUCE LESION VOLUME AND IMPROVE FUNCTIONAL OUTCOME AFTER TRAUMATIC BRAIN INJURY , 2007, Neurosurgery.

[179]  Molly S. Shoichet,et al.  Miniaturized system of neurotrophin patterning for guided regeneration , 2008, Journal of Neuroscience Methods.

[180]  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.

[181]  R. Prinjha,et al.  Neurobiology: Inhibitor of neurite outgrowth in humans , 2000, Nature.

[182]  Charles Tator,et al.  Synthetic hydrogel guidance channels facilitate regeneration of adult rat brainstem motor axons after complete spinal cord transection. , 2004, Journal of neurotrauma.

[183]  K. Popat,et al.  Template synthesized poly(epsilon-caprolactone) nanowire surfaces for neural tissue engineering. , 2010, Biomaterials.

[184]  M. Shoichet,et al.  Guided cell adhesion and outgrowth in peptide-modified channels for neural tissue engineering. , 2005, Biomaterials.

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

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

[187]  Jeff Sakamoto,et al.  Templated agarose scaffolds support linear axonal regeneration. , 2006, Tissue engineering.

[188]  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.

[189]  Dong Wang,et al.  Rheological characterisation of thermogelling chitosan/glycerol-phosphate solutions , 2001 .

[190]  M. Přádný,et al.  Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 4: Growth of rat bone marrow stromal cells in three-dimensional hydrogels with positive and negative surface charges and in polyelectrolyte complexes , 2006, Journal of materials science. Materials in medicine.

[191]  M. Shoichet,et al.  Immobilized concentration gradients of nerve growth factor guide neurite outgrowth. , 2004, Journal of biomedical materials research. Part A.

[192]  Johan Liu,et al.  Electrospun polyurethane scaffolds for proliferation and neuronal differentiation of human embryonic stem cells , 2009, Biomedical materials.

[193]  S. Strittmatter,et al.  Nogo-66 receptor antagonist peptide promotes axonal regeneration , 2002, Nature.

[194]  J. Mcdonald,et al.  Controlled release of neurotrophin-3 from fibrin gels for spinal cord injury. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[195]  Arthur Brown,et al.  Schwann Cell Coculture Improves the Therapeutic Effect of Bone Marrow Stromal Cells on Recovery in Spinal Cord-Injured Mice , 2011, Cell transplantation.

[196]  鈴木 真澄 Tendon chitosan tubes covalently coupled with synthesized laminin peptides facilitate nerve regeneration in vivo , 2003 .

[197]  William R. Stauffer,et al.  Polypyrrole doped with 2 peptide sequences from laminin. , 2006, Biomaterials.

[198]  M. Tuszynski,et al.  Freeze-dried agarose scaffolds with uniaxial channels stimulate and guide linear axonal growth following spinal cord injury. , 2006, Biomaterials.

[199]  M. Tuszynski,et al.  Regeneration of long-tract axons through sites of spinal cord injury using templated agarose scaffolds. , 2010, Biomaterials.

[200]  M. Azari,et al.  Degenerative and regenerative mechanisms governing spinal cord injury , 2004, Neurobiology of Disease.

[201]  Younan Xia,et al.  Electrospun nanofibers for neural tissue engineering. , 2010, Nanoscale.

[202]  Zhaoyang Yang,et al.  The repair of the injured adult rat hippocampus with NT-3-chitosan carriers. , 2010, Biomaterials.

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

[204]  J. Lu,et al.  Molecular self-assembly and applications of designer peptide amphiphiles. , 2010, Chemical Society reviews.

[205]  Jerry Silver,et al.  Regeneration beyond the glial scar , 2004, Nature Reviews Neuroscience.

[206]  R. Borgens,et al.  The Responses of Mammalian Spinal Axons to an Applied DC Voltage Gradient , 1997, Experimental Neurology.