Biomaterials for CNS Injury

  • Teck Chuan Lim
  • Myron Spector
Part of the Springer Series in Translational Stroke Research book series (SSTSR, volume 5)


Given the complexity of the tissue environment after CNS injury, appropriate delivery and deployment of therapeutic agents (e.g. small molecules, nucleic acids, proteins and cells) are as critical as the identification of the therapeutic agents themselves. Biomaterials are non-viable materials devised to interact with biological systems. Taking a plethora of forms ranging from nanoparticles, microspheres, porous scaffolds and hydrogels, biomaterials can be designed to interact with the injured CNS on a molecular, cellular or even tissue level. They have naturally emerged as powerful tools that can navigate therapeutic agents through the spatial and temporal challenges of the ever-evolving milieu in the injured CNS. This chapter highlights the roles that biomaterials play in neuroprotection, repair and regeneration (by protecting molecules and targeting them toward the CNS, sustaining long-term release of drugs and providing structural support for endogenous/transplanted cells) and details the strategies they employ in each of these roles. Overall, the numerous applications of biomaterials in the injured CNS not only illustrate the state of the art but also reflect the trend of biomaterials becoming increasingly engaged in an intimate partnership with therapeutic agents to ultimately materialize effective treatment for CNS injury.


Central Nervous System Injury PLGA Microsphere Central Nervous System Lesion Central Nervous System Parenchyma Injured Central Nervous System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Reddy MK, Labhasetwar V (2009) Nanoparticle-mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia-reperfusion injury. FASEB J 23(5):1384–1395. doi: 10.1096/fj.08-116947 CrossRefPubMedGoogle Scholar
  2. 2.
    Chen H, Spagnoli F, Burris M, Rolland WB, Fajilan A, Dou HY, Tang JP, Zhang JH (2012) Nanoerythropoietin is 10-times more effective than regular erythropoietin in neuroprotection in a neonatal rat model of hypoxia and ischemia. Stroke 43(3):884–887. doi: 10.1161/Strokeaha.111.637090 CrossRefPubMedGoogle Scholar
  3. 3.
    Kawaguchi AT, Fukumoto D, Haida M, Ogata Y, Yamano M, Tsukada H (2007) Liposome-encapsulated hemoglobin reduces the size of cerebral infarction in the rat: evaluation with photochemically induced thrombosis of the middle cerebral artery. Stroke 38(5):1626–1632. doi: 10.1161/STROKEAHA.106.467290 CrossRefPubMedGoogle Scholar
  4. 4.
    Chen CL, Chang SF, Lee D, Yang LY, Lee YH, Hsu CY, Lin SJ, Liaw J (2008) Bioavailability effect of methylprednisolone by polymeric micelles. Pharm Res 25(1):39–47. doi: 10.1007/s11095-007-9484-0 CrossRefPubMedGoogle Scholar
  5. 5.
    Alconcel SNS, Baas AS, Maynard HD (2011) FDA-approved poly(ethylene glycol)-protein conjugate drugs. Polym Chem 2(7):1442–1448. doi: 10.1039/C1py00034a CrossRefGoogle Scholar
  6. 6.
    Owens DE, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307(1):93–102. doi: 10.1016/J.Ijpharm.2005.10.010 CrossRefPubMedGoogle Scholar
  7. 7.
    Calvo P, Gouritin B, Chacun H, Desmaele D, D’Angelo J, Noel JP, Georgin D, Fattal E, Andreux JP, Couvreur P (2001) Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery. Pharm Res 18(8):1157–1166. doi: 10.1023/A:1010931127745 CrossRefPubMedGoogle Scholar
  8. 8.
    Nance EA, Woodworth GF, Sailor KA, Shih TY, Xu QG, Swaminathan G, Xiang D, Eberhart C, Hanes J (2012) A dense poly(ethylene glycol) coating improves penetration of large polymeric nanoparticles within brain tissue. Sci Transl Med 4(149):149ra119CrossRefPubMedGoogle Scholar
  9. 9.
    Gref R, Luck M, Quellec P, Marchand M, Dellacherie E, Harnisch S, Blunk T, Muller RH (2000) ‘Stealth’ corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B Biointerfaces 18(3–4):301–313CrossRefPubMedGoogle Scholar
  10. 10.
    Ishida T, Ichihara M, Wang X, Yamamoto K, Kimura J, Majima E, Kiwada H (2006) Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes. J Control Release 112(1):15–25. doi: 10.1016/j.jconrel.2006.01.005 CrossRefPubMedGoogle Scholar
  11. 11.
    Ishihara T, Maeda T, Sakamoto H, Takasaki N, Shigyo M, Ishida T, Kiwada H, Mizushima Y, Mizushima T (2010) Evasion of the accelerated blood clearance phenomenon by coating of nanoparticles with various hydrophilic polymers. Biomacromolecules 11(10):2700–2706. doi: 10.1021/Bm100754e CrossRefPubMedGoogle Scholar
  12. 12.
    Wang X, Chi N, Tang X (2008) Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting. Eur J Pharm Biopharm 70(3):735–740. doi: 10.1016/j.ejpb.2008.07.005 CrossRefPubMedGoogle Scholar
  13. 13.
    Migliore MM, Vyas TK, Campbell RB, Amiji MM, Waszczak BL (2010) Brain delivery of proteins by the intranasal route of administration: a comparison of cationic liposomes versus aqueous solution formulations. J Pharm Sci 99(4):1745–1761. doi: 10.1002/jps.21939 PubMedGoogle Scholar
  14. 14.
    Karatas H, Aktas Y, Gursoy-Ozdemir Y, Bodur E, Yemisci M, Caban S, Vural A, Pinarbasli O, Capan Y, Fernandez-Megia E, Novoa-Carballal R, Riguera R, Andrieux K, Couvreur P, Dalkara T (2009) A nanomedicine transports a peptide caspase-3 inhibitor across the blood–brain barrier and provides neuroprotection. J Neurosci 29(44):13761–13769. doi: 10.1523/JNEUROSCI.4246-09.2009 CrossRefPubMedGoogle Scholar
  15. 15.
    Liu L, Guo K, Lu J, Venkatraman SS, Luo D, Ng KC, Ling EA, Moochhala S, Yang YY (2008) Biologically active core/shell nanoparticles self-assembled from cholesterol-terminated PEG-TAT for drug delivery across the blood–brain barrier. Biomaterials 29(10):1509–1517. doi: 10.1016/j.biomaterials.2007.11.014 CrossRefPubMedGoogle Scholar
  16. 16.
    Costantino L, Gandolfi F, Tosi G, Rivasi F, Vandelli MA, Forni F (2005) Peptide-derivatized biodegradable nanoparticles able to cross the blood–brain barrier. J Control Release 108(1):84–96. doi: 10.1016/j.jconrel.2005.07.013 CrossRefPubMedGoogle Scholar
  17. 17.
    Ke W, Shao K, Huang R, Han L, Liu Y, Li J, Kuang Y, Ye L, Lou J, Jiang C (2009) Gene delivery targeted to the brain using an Angiopep-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. Biomaterials 30(36):6976–6985. doi: 10.1016/j.biomaterials.2009.08.049 CrossRefPubMedGoogle Scholar
  18. 18.
    Goppert TM, Muller RH (2005) Polysorbate-stabilized solid lipid nanoparticles as colloidal carriers for intravenous targeting of drugs to the brain: comparison of plasma protein adsorption patterns. J Drug Target 13(3):179–187. doi: 10.1080/10611860500071292 CrossRefPubMedGoogle Scholar
  19. 19.
    Gao X, Tao W, Lu W, Zhang Q, Zhang Y, Jiang X, Fu S (2006) Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration. Biomaterials 27(18):3482–3490. doi: 10.1016/j.biomaterials.2006.01.038 CrossRefPubMedGoogle Scholar
  20. 20.
    Gao X, Chen J, Tao W, Zhu J, Zhang Q, Chen H, Jiang X (2007) UEA I-bearing nanoparticles for brain delivery following intranasal administration. Int J Pharm 340(1–2):207–215. doi: 10.1016/j.ijpharm.2007.03.039 CrossRefPubMedGoogle Scholar
  21. 21.
    Heffernan C, Sumer H, Guillemin GJ, Manuelpillai U, Verma PJ (2012) Design and screening of a glial cell-specific, cell penetrating peptide for therapeutic applications in multiple sclerosis. PLoS One 7(9):e45501. doi: 10.1371/journal.pone.0045501 CrossRefPubMedGoogle Scholar
  22. 22.
    Liu JK, Teng Q, Garrity-Moses M, Federici T, Tanase D, Imperiale MJ, Boulis NM (2005) A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting. Neurobiol Dis 19(3):407–418. doi: 10.1016/j.nbd.2005.01.022 CrossRefPubMedGoogle Scholar
  23. 23.
    Lanza GM, Marsh JN, Hu G, Scott MJ, Schmieder AH, Caruthers SD, Pan D, Wickline SA (2010) Rationale for a nanomedicine approach to thrombolytic therapy. Stroke 41(10 suppl):S42–S44. doi: 10.1161/STROKEAHA.110.598656 CrossRefPubMedGoogle Scholar
  24. 24.
    Takamiya M, Miyamoto Y, Yamashita T, Deguchi K, Ohta Y, Abe K (2012) Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- and tissue plasminogen activator-related brain damages in mice. Neuroscience 221:47–55. doi: 10.1016/j.neuroscience.2012.06.060 CrossRefPubMedGoogle Scholar
  25. 25.
    Bitner BR, Marcano DC, Berlin JM, Fabian RH, Cherian L, Culver JC, Dickinson ME, Robertson CS, Pautler RG, Kent TA, Tour JM (2012) Antioxidant carbon particles improve cerebrovascular dysfunction following traumatic brain injury. ACS Nano 6(9):8007–8014. doi: 10.1021/N0302615f CrossRefPubMedGoogle Scholar
  26. 26.
    Pavinatto FJ, Pavinatto A, Caseli L, dos Santos DS, Nobre TM, Zaniquelli MED, Oliveira ON (2007) Interaction of chitosan with cell membrane models at the air-water interface. Biomacromolecules 8(5):1633–1640. doi: 10.1021/Bm0701550 CrossRefPubMedGoogle Scholar
  27. 27.
    Cho Y, Shi R, Ben Borgens R (2010) Chitosan nanoparticle-based neuronal membrane sealing and neuroprotection following acrolein-induced cell injury. J Biol Eng 4(1):2. doi: 10.1186/1754-1611-4-2 CrossRefPubMedGoogle Scholar
  28. 28.
    Gupta D, Tator CH, Shoichet MS (2006) Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials 27(11):2370–2379. doi: 10.1016/J.Biomaterials.2005.11.015 CrossRefPubMedGoogle Scholar
  29. 29.
    Kang CE, Poon PC, Tator CH, Shoichet MS (2009) A new paradigm for local and sustained release of therapeutic molecules to the injured spinal cord for neuroprotection and tissue repair. Tissue Eng Part A 15(3):595–604. doi: 10.1089/Ten.Tea.2007.0349 CrossRefPubMedGoogle Scholar
  30. 30.
    Cooke MJ, Wang YF, Morshead CM, Shoichet MS (2011) Controlled epi-cortical delivery of epidermal growth factor for the stimulation of endogenous neural stem cell proliferation in stroke-injured brain. Biomaterials 32(24):5688–5697. doi: 10.1016/J.Biomaterials.2011.04.032 CrossRefPubMedGoogle Scholar
  31. 31.
    Wang YF, Cooke MJ, Morshead CM, Shoichet MS (2012) Hydrogel delivery of erythropoietin to the brain for endogenous stem cell stimulation after stroke injury. Biomaterials 33(9):2681–2692. doi: 10.1016/J.Biomaterials.2011.12.031 CrossRefPubMedGoogle Scholar
  32. 32.
    Pean JM, Menei P, Morel O, Montero-Menei CN, Benoit JP (2000) Intraseptal implantation of NGF-releasing microspheres promote the survival of axotomized cholinergic neurons. Biomaterials 21(20):2097–2101. doi: 10.1016/S0142-9612(00)00141-1 CrossRefPubMedGoogle Scholar
  33. 33.
    Lee H, McKeon RJ, Bellamkonda RV (2010) Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury. Proc Natl Acad Sci U S A 107(8):3340–3345. doi: 10.1073/Pnas.0905437106 CrossRefPubMedGoogle Scholar
  34. 34.
    Ikada Y, Tabata Y (1998) Protein release from gelatin matrices. Adv Drug Deliv Rev 31(3):287–301CrossRefPubMedGoogle Scholar
  35. 35.
    Nakaguchi K, Jinnou H, Kaneko N, Sawada M, Hikita T, Saitoh S, Tabata Y, Sawamoto K (2012) Growth factors released from gelatin hydrogel microspheres increase new neurons in the adult mouse brain. Stem Cells Int 2012:915160. doi: 10.1155/2012/915160 PubMedGoogle Scholar
  36. 36.
    Sakiyama-Elbert SE, Hubbell JA (2000) Development of fibrin derivatives for controlled release of heparin-binding growth factors. J Control Release 65(3):389–402CrossRefPubMedGoogle Scholar
  37. 37.
    Taylor SJ, Rosenzweig ES, McDonald JW III, Sakiyama-Elbert SE (2006) Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury. J Control Release 113(3):226–235. doi: 10.1016/j.jconrel.2006.05.005 CrossRefPubMedGoogle Scholar
  38. 38.
    Ma J, Tian WM, Hou SP, Xu QY, Spector M, Cui FZ (2007) An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model. Biomed Mater 2(4):233–240. doi: 10.1088/1748-6041/2/4/005 CrossRefPubMedGoogle Scholar
  39. 39.
    Wei YT, He Y, Xu CL, Wang Y, Liu BF, Wang XM, Sun XD, Cui FZ, Xu QY (2010) Hyaluronic acid hydrogel modified with nogo-66 receptor antibody and poly-L-lysine to promote axon regrowth after spinal cord injury. J Biomed Mater Res B Appl Biomater 95(1):110–117. doi: 10.1002/jbm.b.31689 PubMedGoogle Scholar
  40. 40.
    Yano A, Shingo T, Takeuchi A, Yasuhara T, Kobayashi K, Takahashi K, Muraoka K, Matsui T, Miyoshi Y, Hamada H, Date I (2005) Encapsulated vascular endothelial growth factor-secreting cell grafts have neuroprotective and angiogenic effects on focal cerebral ischemia. J Neurosurg 103(1):104–114. doi: 10.3171/jns.2005.103.1.0104 CrossRefPubMedGoogle Scholar
  41. 41.
    Tobias CA, Dhoot NO, Wheatley MA, Tessler A, Murray M, Fischer I (2001) Grafting of encapsulated BDNF-producing fibroblasts into the injured spinal cord without immune suppression in adult rats. J Neurotrauma 18(3):287–301. doi: 10.1089/08977150151070937 CrossRefPubMedGoogle Scholar
  42. 42.
    Winn SR, Lindner MD, Lee A, Haggett G, Francis JM, Emerich DF (1996) Polymer-encapsulated genetically modified cells continue to secrete human nerve growth factor for over one year in rat ventricles: behavioral and anatomical consequences. Exp Neurol 140(2):126–138. doi: 10.1006/exnr.1996.0123 CrossRefPubMedGoogle Scholar
  43. 43.
    Baumann MD, Kang CE, Stanwick JC, Wang Y, Kim H, Lapitsky Y, Shoichet MS (2009) An injectable drug delivery platform for sustained combination therapy. J Control Release 138(3):205–213. doi: 10.1016/j.jconrel.2009.05.009 CrossRefPubMedGoogle Scholar
  44. 44.
    Perale G, Rossi F, Santoro M, Peviani M, Papa S, Llupi D, Torriani P, Micotti E, Previdi S, Cervo L, Sundstrom E, Boccaccini AR, Masi M, Forloni G, Veglianese P (2012) Multiple drug delivery hydrogel system for spinal cord injury repair strategies. J Control Release 159(2):271–280. doi: 10.1016/j.jconrel.2011.12.025 CrossRefPubMedGoogle Scholar
  45. 45.
    Wang Y, Wei YT, Zu ZH, Ju RK, Guo MY, Wang XM, Xu QY, Cui FZ (2011) Combination of hyaluronic acid hydrogel scaffold and PLGA microspheres for supporting survival of neural stem cells. Pharm Res 28(6):1406–1414. doi: 10.1007/s11095-011-0452-3 CrossRefPubMedGoogle Scholar
  46. 46.
    Lin CC, Metters AT (2008) Bifunctional monolithic affinity hydrogels for dual-protein delivery. Biomacromolecules 9(3):789–795. doi: 10.1021/bm700940w CrossRefPubMedGoogle Scholar
  47. 47.
    Tauro JR, Gemeinhart RA (2005) Matrix metalloprotease triggered delivery of cancer chemotherapeutics from hydrogel matrixes. Bioconjug Chem 16(5):1133–1139. doi: 10.1021/bc0501303 CrossRefPubMedGoogle Scholar
  48. 48.
    Jin K, Mao X, Xie L, Galvan V, Lai B, Wang Y, Gorostiza O, Wang X, Greenberg DA (2010) Transplantation of human neural precursor cells in Matrigel scaffolding improves outcome from focal cerebral ischemia after delayed postischemic treatment in rats. J Cereb Blood Flow Metab 30(3):534–544. doi: 10.1038/jcbfm.2009.219 CrossRefPubMedGoogle Scholar
  49. 49.
    Hejcl A, Sedy J, Kapcalova M, Toro DA, Amemori T, Lesny P, Likavcanova-Masinova K, Krumbholcova E, Pradny M, Michalek J, Burian M, Hajek M, Jendelova P, Sykova E (2010) HPMA-RGD hydrogels seeded with mesenchymal stem cells improve functional outcome in chronic spinal cord injury. Stem Cells Dev 19(10):1535–1546. doi: 10.1089/scd.2009.0378 CrossRefPubMedGoogle Scholar
  50. 50.
    Ellis-Behnke RG, Liang YX, You SW, Tay DK, Zhang S, So KF, Schneider GE (2006) Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. Proc Natl Acad Sci U S A 103(13):5054–5059. doi: 10.1073/pnas.0600559103 CrossRefPubMedGoogle Scholar
  51. 51.
    Huang KF, Hsu WC, Chiu WT, Wang JY (2012) Functional improvement and neurogenesis after collagen-GAG matrix implantation into surgical brain trauma. Biomaterials 33(7):2067–2075. doi: 10.1016/j.biomaterials.2011.11.040 CrossRefPubMedGoogle Scholar
  52. 52.
    Park KI, Teng YD, Snyder EY (2002) The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue. Nat Biotechnol 20(11):1111–1117. doi: 10.1038/nbt751 CrossRefPubMedGoogle Scholar
  53. 53.
    Elias PZ, Spector M (2012) Implantation of a collagen scaffold seeded with adult rat hippocampal progenitors in a rat model of penetrating brain injury. J Neurosci Methods 209(1):199–211. doi: 10.1016/j.jneumeth.2012.06.003 CrossRefPubMedGoogle Scholar
  54. 54.
    Cholas RH, Hsu HP, Spector M (2012) The reparative response to cross-linked collagen-based scaffolds in a rat spinal cord gap model. Biomaterials 33(7):2050–2059. doi: 10.1016/j.biomaterials.2011.11.028 CrossRefPubMedGoogle Scholar
  55. 55.
    Zeng X, Zeng YS, Ma YH, Lu LY, Du BL, Zhang W, Li Y, Chan WY (2011) Bone marrow mesenchymal stem cells in a three dimensional gelatin sponge scaffold attenuate inflammation. Promote angiogenesis and reduce cavity formation in experimental spinal cord injury. Cell Transplant 20(11–12):1881–1899. doi: 10.3727/096368911X566181 CrossRefPubMedGoogle Scholar
  56. 56.
    Tate CC, Shear DA, Tate MC, Archer DR, Stein DG, LaPlaca MC (2009) Laminin and fibronectin scaffolds enhance neural stem cell transplantation into the injured brain. J Tissue Eng Regen Med 3(3):208–217. doi: 10.1002/term.154 CrossRefPubMedGoogle Scholar
  57. 57.
    Hou S, Xu Q, Tian W, Cui F, Cai Q, Ma J, Lee IS (2005) The repair of brain lesion by implantation of hyaluronic acid hydrogels modified with laminin. J Neurosci Methods 148(1):60–70. doi: 10.1016/j.jneumeth.2005.04.016 CrossRefPubMedGoogle Scholar
  58. 58.
    Woerly S, Pinet E, de Robertis L, Van Diep D, Bousmina M (2001) Spinal cord repair with PHPMA hydrogel containing RGD peptides (NeuroGel). Biomaterials 22(10):1095–1111CrossRefPubMedGoogle Scholar
  59. 59.
    Wei YT, Tian WM, Yu X, Cui FZ, Hou SP, Xu QY, Lee IS (2007) Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain. Biomed Mater 2(3):S142–S146CrossRefPubMedGoogle Scholar
  60. 60.
    Fukushima K, Enomoto M, Tomizawa S, Takahashi M, Wakabayashi Y, Itoh S, Kuboki Y, Shinomiya K (2008) The axonal regeneration across a honeycomb collagen sponge applied to the transected spinal cord. J Med Dent Sci 55(1):71–79PubMedGoogle Scholar
  61. 61.
    Aota S, Nomizu M, Yamada KM (1994) The short amino acid sequence Pro-His-Ser-Arg-Asn in human fibronectin enhances cell-adhesive function. J Biol Chem 269(40):24756–24761PubMedGoogle Scholar
  62. 62.
    Potter W, Kalil RE, Kao WJ (2008) Biomimetic material systems for neural progenitor cell-based therapy. Front Biosci 13:806–821CrossRefPubMedGoogle Scholar
  63. 63.
    Prang P, Muller R, Eljaouhari A, Heckmann K, Kunz W, Weber T, Faber C, Vroemen M, Bogdahn U, Weidner N (2006) The promotion of oriented axonal regrowth in the injured spinal cord by alginate-based anisotropic capillary hydrogels. Biomaterials 27(19):3560–3569. doi: 10.1016/j.biomaterials.2006.01.053 PubMedGoogle Scholar
  64. 64.
    Stokols S, Sakamoto J, Breckon C, Holt T, Weiss J, Tuszynski MH (2006) Templated agarose scaffolds support linear axonal regeneration. Tissue Eng 12(10):2777–2787. doi: 10.1089/ten.2006.12.2777 CrossRefPubMedGoogle Scholar
  65. 65.
    Chen BK, Knight AM, de Ruiter GCW, Spinner RJ, Yaszemski MJ, Currier BL, Windebank AJ (2009) Axon regeneration through scaffold into distal spinal cord after transection. J Neurotrauma 26(10):1759–1771. doi: 10.1089/Neu.2008.0610 CrossRefPubMedGoogle Scholar
  66. 66.
    Chow WN, Simpson DG, Bigbee JW, Colello RJ (2007) Evaluating neuronal and glial growth on electrospun polarized matrices: bridging the gap in percussive spinal cord injuries. Neuron Glia Biol 3:119–126. doi: 10.1017/S1740925x07000580 CrossRefPubMedGoogle Scholar
  67. 67.
    Hurtado A, Cregg JM, Wang HB, Wendell DF, Oudega M, Gilbert RJ, McDonald JW (2011) Robust CNS regeneration after complete spinal cord transection using aligned poly-L-lactic acid microfibers. Biomaterials 32(26):6068–6079. doi: 10.1016/J.Biomaterials.2011.05.006 PubMedGoogle Scholar
  68. 68.
    Stokols S, Tuszynski MH (2004) The fabrication and characterization of linearly oriented nerve guidance scaffolds for spinal cord injury. Biomaterials 25(27):5839–5846. doi: 10.1016/j.biomaterials.2004.01.041 CrossRefPubMedGoogle Scholar
  69. 69.
    Teng YD, Lavik EB, Qu X, Park KI, Ourednik J, Zurakowski D, Langer R, Snyder EY (2002) Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci U S A 99(5):3024–3029. doi: 10.1073/pnas.052678899 CrossRefPubMedGoogle Scholar
  70. 70.
    Wong DY, Krebsbach PH, Hollister SJ (2008) Brain cortex regeneration affected by scaffold architectures. J Neurosurg 109(4):715–722. doi: 10.3171/JNS/2008/109/10/0715 CrossRefPubMedGoogle Scholar
  71. 71.
    Nisbet DR, Rodda AE, Horne MK, Forsythe JS, Finkelstein DI (2009) Neurite infiltration and cellular response to electrospun polycaprolactone scaffolds implanted into the brain. Biomaterials 30(27):4573–4580CrossRefPubMedGoogle Scholar
  72. 72.
    Miller C, Jeftinija S, Mallapragada S (2002) Synergistic effects of physical and chemical guidance cues on neurite alignment and outgrowth on biodegradable polymer substrates. Tissue Eng 8(3):367–378. doi: 10.1089/107632702760184646 CrossRefPubMedGoogle Scholar
  73. 73.
    Mahoney MJ, Chen RR, Tan J, Saltzman WM (2005) The influence of microchannels on neurite growth and architecture. Biomaterials 26(7):771–778. doi: 10.1016/j.biomaterials.2004.03.015 CrossRefPubMedGoogle Scholar
  74. 74.
    Dowell-Mesfin NM, Abdul-Karim MA, Turner AM, Schanz S, Craighead HG, Roysam B, Turner JN, Shain W (2004) Topographically modified surfaces affect orientation and growth of hippocampal neurons. J Neural Eng 1(2):78–90. doi: 10.1088/1741-2560/1/2/003 CrossRefPubMedGoogle Scholar
  75. 75.
    Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689. doi: 10.1016/j.cell.2006.06.044 CrossRefPubMedGoogle Scholar
  76. 76.
    Saha K, Keung AJ, Irwin EF, Li Y, Little L, Schaffer DV, Healy KE (2008) Substrate modulus directs neural stem cell behavior. Biophys J 95(9):4426–4438. doi: 10.1529/biophysj.108.132217 CrossRefPubMedGoogle Scholar
  77. 77.
    Leipzig ND, Shoichet MS (2009) The effect of substrate stiffness on adult neural stem cell behavior. Biomaterials 30(36):6867–6878. doi: 10.1016/j.biomaterials.2009.09.002 CrossRefPubMedGoogle Scholar
  78. 78.
    Lee YS, Arinzeh TL (2012) The influence of piezoelectric scaffolds on neural differentiation of human neural stem/progenitor cells. Tissue Eng Part A 18(19–20):2063–2072. doi: 10.1089/ten.TEA.2011.0540 CrossRefPubMedGoogle Scholar
  79. 79.
    Cellot G, Cilia E, Cipollone S, Rancic V, Sucapane A, Giordani S, Gambazzi L, Markram H, Grandolfo M, Scaini D, Gelain F, Casalis L, Prato M, Giugliano M, Ballerini L (2009) Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts. Nat Nanotechnol 4(2):126–133. doi: 10.1038/nnano.2008.374 CrossRefPubMedGoogle Scholar
  80. 80.
    Cellot G, Toma FM, Varley ZK, Laishram J, Villari A, Quintana M, Cipollone S, Prato M, Ballerini L (2011) Carbon nanotube scaffolds tune synaptic strength in cultured neural circuits: novel frontiers in nanomaterial-tissue interactions. J Neurosci 31(36):12945–12953. doi: 10.1523/JNEUROSCI.1332-11.2011 CrossRefPubMedGoogle Scholar
  81. 81.
    Lim TC, Toh WS, Wang LS, Kurisawa M, Spector M (2012) The effect of injectable gelatin-hydroxyphenylpropionic acid hydrogel matrices on the proliferation, migration, differentiation and oxidative stress resistance of adult neural stem cells. Biomaterials 33(12):3446–3455. doi: 10.1016/j.biomaterials.2012.01.037 CrossRefPubMedGoogle Scholar
  82. 82.
    Bencherif SA, Sands RW, Bhatta D, Arany P, Verbeke CS, Edwards DA, Mooney DJ (2012) Injectable preformed scaffolds with shape-memory properties. Proc Natl Acad Sci U S A 109(48):19590–19595. doi: 10.1073/pnas.1211516109 CrossRefPubMedGoogle Scholar
  83. 83.
    Johnson PJ, Tatara A, Shiu A, Sakiyama-Elbert SE (2010) 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. Cell Transplant 19(1):89–101. doi: 10.3727/096368909X477273 CrossRefPubMedGoogle Scholar
  84. 84.
    Bible E, Qutachi O, Chau DY, Alexander MR, Shakesheff KM, Modo M (2012) Neo-vascularization of the stroke cavity by implantation of human neural stem cells on VEGF-releasing PLGA microparticles. Biomaterials 33(30):7435–7446. doi: 10.1016/j.biomaterials.2012.06.085 CrossRefPubMedGoogle Scholar
  85. 85.
    Cholas R, Hsu HP, Spector M (2012) Collagen scaffolds incorporating select therapeutic agents to facilitate a reparative response in a standardized hemiresection defect in the rat spinal cord. Tissue Eng Part A 18(19–20):2158–2172. doi: 10.1089/ten.TEA.2011.0577 CrossRefPubMedGoogle Scholar
  86. 86.
    Guo X, Zahir T, Mothe A, Shoichet MS, Morshead CM, Katayama Y, Tator CH (2012) The effect of growth factors and soluble nogo-66 receptor protein on transplanted neural stem/progenitor survival and axonal regeneration after complete transection of rat spinal cord. Cell Transplant 21(6):1177–1197. doi: 10.3727/096368911X612503 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Tissue Engineering/Orthopedic SurgeryVA Boston Healthcare System/Brigham and Women’s Hospital/Harvard Medical SchoolBostonUSA
  2. 2.Massachusetts Institute of Technology, Harvard-MIT Division of Health Sciences and TechnologyCambridgeUSA

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