Hydrogels in spinal cord injury repair strategies

ACS Chemical Neuroscience

Volumn 2, Issue 7, 2011, Pages 336-345

  Perale, Giuseppe ^a,b   Rossi, Filippo ^a,b   Sundstrom, Erik ^c   Bacchiega, Sara ^d   Masi, Maurizio ^a   Forloni, Gianluigi ^b   Veglianese, Pietro ^b  

^a POLITECNICO DI MILANO   (Italy)

^b MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^c KAROLINSKA INSTITUTE   (Sweden)

^d MiTo Technology Srl   (Italy)

Author keywords

Hydrogels; polymers; regenerative medicine; scaffold; spinal cord injury; tissue engineering

Indexed keywords

CHITOSAN; HYALURONIC ACID; MACROGOL; POLYLYSINE; POLYMER;

DRUG DELIVERY SYSTEM; HYDROGEL; PRIORITY JOURNAL; REGENERATIVE MEDICINE; REVIEW; SPINAL CORD INJURY; SPINAL CORD REGENERATION; SYNTHETIC FIBER;

ANIMALS; BIOCOMPATIBLE MATERIALS; HUMANS; HYDROGELS; REGENERATIVE MEDICINE; SPINAL CORD INJURIES;

EID: 79959691162     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn200030w     Document Type: Review

References (174)

1. van den Berg, M. E. L., Castellote, J. M., de Pedro-Cuesta, J., and Mahillo-Fernandez, I. (2010) Survival after Spinal Cord Injury: A Systematic Review J. Neurotrauma 27, 1517-1528
2. van den Berg, M. E. L., Castellote, J. M., Mahillo-Fernandez, I., and de Pedro-Cuesta, J. (2010) Incidence of Spinal Cord Injury Worldwide: A Systematic Review Neuroepidemiology 34, 184-192
3. Abu-Rub, M., McMahon, S., Zeugolis, D. I., Windebank, A., and Pandit, A. (2010) Spinal cord injury in vitro: modelling axon growth inhibition Drug Discovery Today 15, 436-443
4. Ditunno, J. F. (2010) Outcome measures: evolution in clinical trials of neurological/functional recovery in spinal cord injury Spinal Cord 48, 674-684
5. Steward, O., Schauwecker, P. E., Guth, L., Zhang, Z. Y., Fujiki, M., Inman, D., Wrathall, J., Kempermann, G., Gage, F. H., Saatman, K. E., Raghupathi, R., and McIntosh, T. (1999) Genetic approaches to neurotrauma research: Opportunities and potential pitfalls of murine models Exp. Neurol. 157, 19-42 (Pubitemid 29226866)
6. Kubinova, S. and Sykova, E. (2010) Nanotechnology for treatment of stroke and spinal cord injury Nanomedicine 5, 99-108
7. Kubinova, S. and Sykova, E. (2010) Nanotechnologies in regenerative medicine Minimally Invasive Ther. 19, 144-156
8. Fawcett, J. W. and Asher, R. A. (1999) The glial scar and central nervous system repair Brain Res. Bull. 49, 377-391 (Pubitemid 29385505)
9. McDonald, J. W., Gottlieb, D. I., and Choi, D. W. (2000) What is a functional recovery after spinal cord injury? Nat. Med. 6, 358-358
10. Bradbury, E. J. and Carter, L. M. (2011) Manipulating the glial scar: Chondroitinase ABC as a therapy for spinal cord injury Brain Res. Bull. 84, 306-316
11. Bradbury, E. J. and McMahon, S. B. (2006) Opinion-Spinal cord repair strategies: why do they work? Nat. Rev. Neurosci. 7, 644-653 (Pubitemid 44106746)
12. Cao, K., Huang, L., Liu, J. W., An, H., Shu, Y., and Han, Z. M. (2010) Inhibitory effects of high-dose methylprednisolone on bacterial translocation from gut and endotoxin release following acute spinal cord injury-induced paraplegia in rats Neural Regener. Res. 5, 456-460
13. Bracken, M. B., Shepard, M. J., Collins, W. F., Holford, T. R., Young, W., Piepmeier, J., Leosummers, L., Baskin, D. S., Eisenberg, H. M., Flamm, E., Marshall, L. F., Maroon, J., Wilberger, J., Perot, P. L., Sonntag, V. K. H., Wagner, F. C., and Winn, H. R. (1990) a Randomized, Controlled Trial of Methylprednisolone or Naloxone in the Treatment of Acute Spinal-Cord Injury New Engl. J. Med. 323, 1209-1209
14. Kim, Y. T., Caldwell, J. M., and Bellamkonda, R. V. (2009) Nanoparticle-mediated local delivery of methylprednisolone after spinal cord injury Biomaterials 30, 2582-2590
15. Green, P. S. and Simpkins, J. W. (2000) Neuroprotective effects of estrogens: potential mechanisms of action Int. J. Dev. Neurosci. 18, 347-358 (Pubitemid 30243066)
16. Langer, R. (2009) Perspectives and Challenges in Tissue Engineering and Regenerative Medicine Adv. Mater. 21, 3235-3236
17. Langer, R. and Vacanti, J. P. (1993) Tissue Engineering Science 260, 920-926 (Pubitemid 23209960)
18. Peppas, N. A. and Langer, R. (1994) New Challenges in Biomaterials Science 263, 1715-1720 (Pubitemid 24131582)
19. Salewski, R. P. F., Eftekharpour, E., and Fehlings, M. G. (2010) Are Induced Pluripotent Stem Cells the Future of Cell-Based Regenerative Therapies for Spinal Cord Injury? J. Cell. Physiol. 222, 515-521
20. Stocum, D. L. (2005) Stem cells in CNS and cardiac regeneration Regener. Med. I: Theor., Models Methods 93, 135-159 (Pubitemid 44617150)
21. Taha, M. F. (2010) Cell based-gene delivery approaches for the treatment of spinal cord injury and neurodegenerative disorders Curr. Stem Cell. Res. Ther. 5, 23-36
22. Sakurada, K., McDonald, F. M., and Shimada, F. (2008) Regenerative medicine and stem cell based drug discovery Angew. Chem., Int. Ed. 47, 5718-5738
23. Sahni, V. and Kessler, J. A. (2010) Stem cell therapies for spinal cord injury Nat. Rev. Neurol. 6, 363-372
24. Little, L., Healy, K. E., and Schaffer, D. (2008) Engineering biomaterials for synthetic neural stem cell microenvironments Chem. Rev. 108, 1787-1796 (Pubitemid 351796410)
25. Soria, J. M., Ramos, C. M., Sanchez, M. S., Benavent, V., Fernandez, A. C., Ribelles, J. L. G., Verdugo, J. M. G., Pradas, M. M., and Barcia, J. A. (2006) Survival and differentiation of embryonic neural explants on different biomaterials J. Biomed. Mater. Res., Part A 79A, 495-502 (Pubitemid 44845162)
26. Varghese, O. P., Sun, W. L., Hilborn, J., and Ossipov, D. A. (2009) In Situ Cross-Linkable High Molecular Weight Hyaluronan-Bisphosphonate Conjugate for Localized Delivery and Cell-Specific Targeting: A Hydrogel Linked Prodrug Approach J. Am. Chem. Soc. 131, 8781-8784
27. Hellal, F., Hurtado, A., Ruschel, J., Flynn, K. C., Laskowski, C. J., Umlauf, M., Kapitein, L. C., Strikis, D., Lemmon, V., Bixby, J., Hoogenraad, C. C., and Bradke, F. (2011) Microtubule Stabilization Reduces Scarring and Causes Axon Regeneration After Spinal Cord Injury Science 331, 928-931
28. Atala, R., Langer, R., Thomson, J., and Nerem, R. (2008) Principles of regenerative medicine, Academic Press, Burlington, MA.
29. Mantsos, T., Chatzistavrou, X., Roether, J. A., Hupa, L., Arstila, H., and Boccaccini, A. R. (2009) Non-crystalline composite tissue engineering scaffolds using boron-containing bioactive glass and poly(D,L-lactic acid) coatings Biomed. Mater. 4, 055002
30. Rezwan, K., Chen, Q. Z., Blaker, J. J., and Boccaccini, A. R. (2006) Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering Biomaterials 27, 3413-3431
31. Hu, B. H., Su, J., and Messersmith, P. B. (2009) Hydrogels Cross-Linked by Native Chemical Ligation Biomacromolecules 10, 2194-2200
32. Blaker, J. J., Bismarck, A., Boccaccini, A. R., Young, A. M., and Nazhat, S. N. (2010) Premature degradation of poly(alpha-hydroxyesters) during thermal processing of Bioglass (R)-containing composites Acta Biomater. 6, 756-762
33. Nakamatsu, J., Torres, F. G., Troncoso, O. P., Yuan, M. L., and Boccaccini, A. R. (2006) Processing and characterization of porous structures from chitosan and starch for tissue engineering scaffolds Biomacromolecules 7, 3345-3355 (Pubitemid 46111789)
34. Engel, E., Michiardi, A., Navarro, M., Lacroix, D., and Planell, J. A. (2008) Nanotechnology in regenerative medicine: the materials side Trends Biotechnol. 26, 39-47 (Pubitemid 350298598)
35. Yu, L. and Ding, J. D. (2008) Injectable hydrogels as unique biomedical materials Chem. Soc. Rev. 37, 1473-1481
36. Slaughter, B. V., Khurshid, S. S., Fisher, O. Z., Khademhosseini, A., and Peppas, N. A. (2009) Hydrogels in Regenerative Medicine Adv. Mater. 21, 3307-3329
37. Luo, Y. and Shoichet, M. S. (2004) A photolabile hydrogel for guided three-dimensional cell growth and migration Nat. Mater. 3, 249-253
38. Thonhoff, J. R., Lou, D. I., Jordan, P. M., Zhao, X., and Wu, P. (2008) Compatibility of human fetal neural stem cells with hydrogel biomaterials in vitro Brain Res. 1187, 42-51 (Pubitemid 350191810)
39. Schmidt, J. J., Rowley, J., and Kong, H. J. (2008) Hydrogels used for cell-based drug delivery J. Biomed. Mater. Res., Part A 87A, 1113-1122
40. Annabi, N., Nichol, J. W., Zhong, X., Ji, C. D., Koshy, S., Khademhosseini, A., and Dehghani, F. (2010) Controlling the Porosity and Microarchitecture of Hydrogels for Tissue Engineering Tissue Eng., Part B 16, 371-383
41. Kwon, B. K., Sekhon, L. H., and Fehlings, M. G. (2010) Emerging Repair, Regeneration, and Translational Research Advances for Spinal Cord Injury Spine 35, S263-S270
42. Perale, G., Bianco, F., Giordano, C., Matteoli, M., Masi, M., and Cigada, A. (2008) Engineering injured spinal cord with bone marrow-derived stem cells and hydrogel-based matrices: a glance at the state of the art J. Appl. Biomater. Biomech. 6, 1-8
43. Hejcl, A., Lesny, P., Pradny, M., Michalek, J., Jendelova, P., Stulik, J., and Sykova, E. (2008) Biocompatible Hydrogels in Spinal Cord Injury Repair Physiol. Res. 57, S121-S132
44. Potter, W., Kalil, R. E., and Kao, W. J. (2008) Biomimetic material systems for neural progenitor cell-based therapy Front. Biosci. 13, 806-821 (Pubitemid 351594730)
45. Zhong, Y. H. and Bellamkonda, R. V. (2008) Biomaterials for the central nervous system J. R. Soc. Interface 5, 957-975 (Pubitemid 352020060)
46. Drury, J. L. and Mooney, D. J. (2003) Hydrogels for tissue engineering: scaffold design variables and applications Biomaterials 24, 4337-4351 (Pubitemid 36960132)
47. Griffith, L. G. and Naughton, G. (2002) Tissue engineering-Current challenges and expanding opportunities Science 295, 1009-1014
48. Hoffman, A. S. (2002) Hydrogels for biomedical applications Adv. Drug Delivery Rev. 54, 3-12 (Pubitemid 34081178)
49. Shoichet, M. S. (2010) Polymer Scaffolds for Biomaterials Applications Macromolecules 43, 581-591
50. Malafaya, P. B., Silva, G. A., and Reis, R. L. (2007) Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications Adv. Drug Delivery Rev. 59, 207-233 (Pubitemid 46879967)
51. Tabata, Y. (2009) Biomaterial technology for tissue engineering applications J. R. Soc. Interface 6, S311-S324
52. Mano, J. F., Silva, G. A., Azevedo, H. S., Malafaya, P. B., Sousa, R. A., Silva, S. S., Boesel, L. F., Oliveira, J. M., Santos, T. C., Marques, A. P., Neves, N. M., and Reis, R. L. (2007) Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends J. R. Soc. Interface 4, 999-1030 (Pubitemid 350303872)
53. Nisbet, D. R., Crompton, K. E., Horne, M. K., Finkelstein, D. I., and Forsythe, J. S. (2008) Neural tissue engineering of the CNS using hydrogels J. Biomed. Mater. Res., Part B 87B, 251-263
54. Hynd, M. R., Turner, J. N., and Shain, W. (2007) Applications of hydrogels for neural cell engineering J. Biomater. Sci., Polym. Ed. 18, 1223-1244 (Pubitemid 47556669)
55. Chung, H. J. and Park, T. G. (2007) Surface engineered and drug releasing pre-fabricated scaffolds for tissue engineering Adv. Drug Delivery Rev. 59, 249-262 (Pubitemid 46879969)
56. Willerth, S. M. and Sakiyama-Elbert, S. E. (2007) Approaches to neural tissue engineering using scaffolds for drug delivery Adv. Drug Delivery Rev. 59, 325-338 (Pubitemid 46879972)
57. Kretlow, J. D., Klouda, L., and Mikos, A. G. (2007) Injectable matrices and scaffolds for drug delivery in tissue engineering Adv. Drug Delivery Rev. 59, 263-273 (Pubitemid 46879970)
58. von Euler, M., Janson, A. M., Larsen, J. O., Seiger, A., Forno, L., Bunge, M. B., and Sundstrom, E. (2002) Spontaneous axonal regeneration in rodent spinal cord after ischemic injury J. Neuropathol. Exp. Neurol. 61, 64-75 (Pubitemid 34027721)
59. Shanbhag, M. S., Lathia, J. D., Mughal, M. R., Francis, N. L., Pashos, N., Mattson, M. P., and Wheatley, M. A. (2010) Neural Progenitor Cells Grown on Hydrogel Surfaces Respond to the Product of the Transgene of Encapsulated Genetically Engineered Fibroblasts Biomacromolecules 11, 2936-2943
60. Nisbet, D. R., Rodda, A. E., Horne, M. K., Forsythe, J. S., and Finkelstein, D. I. (2010) Implantation of Functionalized Thermally Gelling Xyloglucan Hydrogel Within the Brain: Associated Neurite Infiltration and Inflammatory Response Tissue Eng., Part A 16, 2833-2842
61. Hsieh, A., Zahir, T., Lapitsky, Y., Amsden, B., Wan, W. K., and Shoichet, M. S. (2010) Hydrogel/electrospun fiber composites influence neural stem/progenitor cell fate Soft Matter 6, 2227-2237
62. Park, J., Lim, E., Back, S., Na, H., Park, Y., and Sun, K. (2010) Nerve regeneration following spinal cord injury using matrix metalloproteinase- sensitive, hyaluronic acid-based biomimetic hydrogel scaffold containing brain-derived neurotrophic factor J. Biomed. Mater. Res., Part A 93A, 1091-1099
63. Gu, H. G., Yue, Z. L., Leong, W. S., Nugraha, B., and Tan, L. P. (2010) Control of in vitro neural differentiation of mesenchymal stem cells in 3D macroporous, cellulosic hydrogels Regener. Med. 5, 245-253
64. Wang, L. S., Chung, J. E., Chan, P. P. Y., and Kurisawa, M. (2010) Injectable biodegradable hydrogels with tunable mechanical properties for the stimulation of neurogenesic differentiation of human mesenchymal stem cells in 3D culture Biomaterials 31, 1148-1157
65. Pan, L. J., Ren, Y. J., Cui, F. Z., and Xu, Q. Y. (2009) Viability and Differentiation of Neural Precursors on Hyaluronic Acid Hydrogel Scaffold J. Neurosci. Res. 87, 3207-3220
66. Banerjee, A., Arha, M., Choudhary, S., Ashton, R. S., Bhatia, S. R., Schaffer, D. V., and Kane, R. S. (2009) The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells Biomaterials 30, 4695-4699
67. Nisbet, D. R., Moses, D., Gengenbach, T. R., Forsythe, J. S., Finkelstein, D. I., and Horne, M. K. (2009) Enhancing neurite outgrowth from primary neurones and neural stem cells using thermoresponsive hydrogel scaffolds for the repair of spinal cord injury J. Biomed. Mater. Res., Part A 89A, 24-35
68. Willerth, S. M., Faxel, T. E., Gottlieb, D. I., and Sakiyama-Elbert, S. E. (2007) The effects of soluble growth factors on embryonic stem cell differentiation inside of fibrin scaffolds Stem Cells 25, 2235-2244 (Pubitemid 47480482)
69. Novikova, L. N., Mosahebi, A., Wiberg, M., Terenghi, G., Kellerth, J. O., and Novikov, L. N. (2006) Alginate hydrogel and matrigel as potential cell carriers for neurotransplantation J. Biomed. Mater. Res., Part A 77A, 242-252 (Pubitemid 47233525)
70. Stokols, S., Sakamoto, J., Breckon, C., Holt, T., Weiss, J., and Tuszynski, M. H. (2006) Templated agarose scaffolds support linear axonal regeneration Tissue Eng. 12, 2777-2787 (Pubitemid 46141246)
71. Stokols, S. and Tuszynski, M. H. (2006) Freeze-dried agarose scaffolds with uniaxial channels stimulate and guide linear axonal growth following spinal cord injury Biomaterials 27, 443-451 (Pubitemid 41457247)
72. Prang, P., Muller, R., Eljaouhari, A., Heckmann, K., Kunz, W., Weber, T., Faber, C., Vroemen, M., Bogdahn, U., and Weidner, N. (2006) The promotion of oriented axonal regrowth in the injured spinal cord by alginate-based anisotropic capillary hydrogels Biomaterials 27, 3560-3569
73. Lee, H., McKeon, R. J., and Bellamkonda, R. V. (2010) Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury Proc. Natl. Acad. Sci. U.S.A. 107, 3340-3345
74. Chvatal, S. A., Kim, Y. T., Bratt-Leal, A. M., Lee, H. J., and Bellamkonda, R. V. (2008) Spatial distribution and acute anti-inflammatory effects of Methylprednisolone after sustained local delivery to the contused spinal cord Biomaterials 29, 1967-1975
75. Jain, A., McKeon, R. J., Brady-Kalnay, S. M., and Bellamkonda, R. V. (2011) Sustained Delivery of Activated Rho GTPases and BDNF Promotes Axon Growth in CSPG-Rich Regions Following Spinal Cord Injury PloS One 6, 1-12
76. Jain, A., Kim, Y. T., McKeon, R. J., and Bellamkonda, R. V. (2006) In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury Biomaterials 27, 497-504 (Pubitemid 41457252)
77. Zuidema, J. M., Pap, M. M., Jaroch, D. B., Morrison, F. A., and Gilbert, R. J. (2011) Fabrication and characterization of tunable polysaccharide hydrogel blends for neural repair Acta Biomater. 7, 1634-1643
78. Ashton, R. S., Banerjee, A., Punyani, S., Schaffer, D. V., and Kane, R. S. (2007) Scaffolds based on degradable alginate hydrogels and poly(lactide- co -glycolide) microspheres for stem cell culture Biomaterials 28, 5518-5525 (Pubitemid 47599644)
79. Crompton, K. E., Goud, J. D., Bellamkonda, R. V., Gengenbach, T. R., Finkelstein, D. I., Horne, M. K., and Forsythe, J. S. (2007) Polylysine-functionalised thermoresponsive chitosan hydrogel for neural tissue engineering Biomaterials 28, 441-449 (Pubitemid 44740107)
80. Horn, E. M., Beaumont, M., Shu, X. Z., Harvey, A., Prestwich, G. D., Horn, K. M., Gibson, A. R., Preul, M. C., and Panitch, A. (2007) Influence of cross-linked hyaluronic acid hydrogels on neurite outgrowth and recovery from spinal cord injury J. Neurosurg.: Spine 6, 133-140 (Pubitemid 47066056)
81. Iwata, A., Browne, K. D., Pfister, B. J., Gruner, J. A., and Smith, D. H. (2006) Long-term survival and outgrowth of mechanically engineered nervous tissue constructs implanted into spinal cord lesions Tissue Eng. 12, 101-110
82. Pfister, B. J., Iwata, A., Taylor, A. G., Wolf, J. A., Meaney, D. F., and Smith, D. H. (2006) Development of transplantable nervous tissue constructs comprised of stretch-grown axons J. Neurosci. Methods 153, 95-103
83. Hiraoka, M., Kato, K., Nakaji-Hirabayashi, T., and Iwata, H. (2009) Enhanced Survival of Neural Cells Embedded in Hydrogels Composed of Collagen and Laminin-Derived Cell Adhesive Peptide Bioconjugate Chem. 20, 976-983
84. Semino, C. E., Kasahara, J., Hayashi, Y., and Zhang, S. G. (2004) Entrapment of migrating hippocampal neural cells in three-dimensional peptide nanofiber scaffold Tissue Eng. 10, 643-655 (Pubitemid 38580284)
85. Silva, N. A., Salgado, A. J., Sousa, R. A., Oliveira, J. T., Pedro, A. J., Leite-Almeida, H., Cerqueira, R., Almeida, A., Mastronardi, F., Mano, J. F., Neves, N. M., Sousa, N., and Reis, R. L. (2010) Development and Characterization of a Novel Hybrid Tissue Engineering-Based Scaffold for Spinal Cord Injury Repair Tissue Eng., PartA 16, 45-54
86. Wei, Y. T., He, Y., Xu, C. L., Wang, Y., Liu, B. F., Wang, X. M., Sun, X. D., Cui, F. Z., and Xu, Q. Y. (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., Part B 95B, 110-117
87. Wei, Y. T., Tian, W. M., Yu, X., Cui, F. Z., Hou, S. P., Xu, Q. Y., and Lee, I. S. (2007) Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain Biomed. Mater. 2, S142-S146
88. Tian, W. M., Zhang, C. L., Hou, S. P., Yu, X., Cui, F. Z., Xu, Q. Y., Sheng, S. L., Cui, H., and Li, H. D. (2005) Hyaluronic acid hydrogel as Nogo-66 receptor antibody delivery system for the repairing of injured rat brain: in vitro J. Controlled Release 102, 13-22 (Pubitemid 40093772)
89. Hou, S., Tian, W., Xu, Q., Cui, F., Zhang, J., Lu, Q., and Zhao, C. (2006) 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 Neuroscience 137, 519-529 (Pubitemid 43031517)
90. Baumann, M. D., Kang, C. E., Tator, C. H., and Shoichet, M. S. (2010) Intrathecal delivery of a polymeric nanocomposite hydrogel after spinal cord injury Biomaterials 31, 7631-7639
91. Wang, Y. F., Lapitsky, Y., Kang, C. E., and Shoichet, M. S. (2009) Accelerated release of a sparingly soluble drug from an injectable hyaluronan-methylcellulose hydrogel J. Controlled Release 140, 218-223
92. Baumann, M. D., Kang, C. E., Stanwick, J. C., Wang, Y. F., Kim, H., Lapitsky, Y., and Shoichet, M. S. (2009) An injectable drug delivery platform for sustained combination therapy J. Controlled Release 138, 205-213
93. Reynolds, L. F., Bren, M. C., Wilson, B. C., Gibson, G. D., Shoichet, M. S., and Murphy, R. J. L. (2008) Transplantation of porous tubes following spinal cord transection improves hindlimb function in the rat Spinal Cord 46, 58-64
94. Shoichet, M. S., Tator, C. H., Poon, P., Kang, C., and Baumann, M. D. (2007) Intrathecal drug delivery strategy is safe and efficacious for localized delivery to the spinal cord Prog. Brain Res. 161, 385-392 (Pubitemid 47017416)
95. Kang, C. E., Poon, P. C., Tator, C. H., and Shoichet, M. S. (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, 595-604
96. Brannvall, K., Bergman, K., Wallenquist, U., Svahn, S., Bowden, T., Hilborn, J., and Forsberg-Nilsson, K. (2007) Enhanced neuronal differentiation in a three-dimensional collagen-hyaluronan matrix J. Neurosci. Res. 85, 2138-2146 (Pubitemid 47172145)
97. Coviello, T., Grassi, M., Palleschi, A., Bocchinfuso, G., Coluzzi, G., Banishoeib, F., and Alhaique, F. (2005) A new scleroglucan/borax hydrogel: swelling and drug release studies Int. J. Pharm. 289, 97-107 (Pubitemid 40093545)
98. Hejcl, A., Lesny, P., Pradny, M., Sedy, J., Zamecnik, J., Jendelova, P., Michalek, J., and Sykova, E. (2009) 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 J. Mater. Sci.: Mater. Med. 20, 1571-1577
99. Horne, M. K., Nisbet, D. R., Forsythe, J. S., and Parish, C. L. (2010) Three-Dimensional Nanofibrous Scaffolds Incorporating Immobilized BDNF Promote Proliferation and Differentiation of Cortical Neural Stem Cells Stem Cells Dev. 19, 843-852
100. Mallett, A. G. and Korbutt, G. S. (2009) Alginate Modification Improves Long-Term Survival and Function of Transplanted Encapsulated Islets Tissue Eng., Part A 15, 1301-1309
101. Wilson, J. T. and Chaikof, E. L. (2008) Challenges and emerging technologies in the immunoisolation of cells and tissues Adv. Drug Delivery Rev. 60, 124-145 (Pubitemid 350245691)
102. Kulseng, B., Thu, B., Espevik, T., and SkjakBraek, G. (1997) Alginate polylysine microcapsules as immune barrier: Permeability of cytokines and immunoglobulins over the capsule membrane Cell Transplant. 6, 387-394 (Pubitemid 27319157)
103. Hejcl, A., Sedy, J., Kapcalova, M., Toro, D. A., Amemori, T., Lesny, P., Likavcanova-Masinova, K., Krumbholcova, E., Pradny, M., Michalek, J., Burian, M., Hajek, M., Jendelova, P., and Sykova, E. (2010) HPMA-RGD Hydrogels Seeded with Mesenchymal Stem Cells Improve Functional Outcome in Chronic Spinal Cord Injury Stem Cells Dev. 19, 1535-1546
104. Lampe, K. J., Mooney, R. G., Bjugstad, K. B., and Mahoney, M. J. (2010) Effect of macromer weight percent on neural cell growth in 2D and 3D nondegradable PEG hydrogel culture J. Biomed. Mater. Res., Part A 94A, 1162-1171
105. Ali, O. A., Huebsch, N., Cao, L., Dranoff, G., and Mooney, D. J. (2009) Infection-mimicking materials to program dendritic cells in situ Nat. Mater. 8, 151-158
106. Comolli, N., Neuhuber, B., Fischer, I., and Lowman, A. (2009) In vitro analysis of PNIPAAm-PEG, a novel, injectable scaffold for spinal cord repair Acta Biomater. 5, 1046-1055
107. Rauch, M. F., Hynes, S. R., Bertram, J., Redmond, A., Robinson, R., Williams, C., Xu, H., Madri, J. A., and Lavik, E. B. (2009) Engineering angiogenesis following spinal cord injury: a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood-spinal cord barrier Eur. J. Neurosci. 29, 132-145
108. Rauch, M. F., Michaud, M., Xu, H., Madri, J. A., and Lavik, E. B. (2008) Co-culture of primary neural progenitor and endothelial cells in a macroporous gel promotes stable vascular networks in vivo J. Biomater. Sci., Polym. Ed. 19, 1469-1485
109. Sykova, E., Jendelova, P., Hejcl, A., Kozubenko, N., and Amemori, T. (2010) Stem Cells and Hydrogel Bridges for the Treatment of Acute and Chronic Spinal Cord Injury Cell Transplant. 19, 366-366
110. Sykova, E., Jendelova, P., Urdzikova, L., Lesny, P., and Hejcl, A. (2006) Bone marrow stem cells and polymer hydrogels-two strategies for spinal cord injury repair Cell. Mol. Neurobiol. 26, 1113-1129 (Pubitemid 44924034)
111. Hejcl, A., Urdzikova, L., Sedy, J., Lesny, P., Pradny, M., Michalek, J., Burian, M., Hajek, M., Zamecnik, J., Jendelova, P., and Sykova, E. (2008) Acute and delayed implantation of positively charged 2-hydroxyethyl methacrylate scaffolds in spinal cord injury in the rat J. Neurosurg.: Spine 8, 67-73
112. Katayama, Y., Montenegro, R., Freier, T., Midha, R., Belkas, J. S., and Shoichet, M. S. (2006) Coil-reinforced hydrogel tubes promote nerve regeneration equivalent to that of nerve autografts Biomaterials 27, 505-518 (Pubitemid 41457253)
113. Nomura, H., Katayama, Y., Shoichet, M. S., and Tator, C. H. (2006) Complete spinal cord transection treated by implantation of a reinforced synthetic hydrogel channel results in syringomyelia and caudal migration of the rostral stump Neurosurgery 59, 183-192 (Pubitemid 44024376)
114. Tsai, E. C., Dalton, P. D., Shoichet, M. S., and Tator, C. H. (2006) Matrix inclusion within synthetic hydrogel guidance channels improves specific supraspinal and local axonal regeneration after complete spinal cord transection Biomaterials 27, 519-533 (Pubitemid 41457254)
115. Rodriguez-Tenreiro, C., Alvarez-Lorenzo, C., Rodriguez-Perez, A., Concheiro, A., and Torres-Labandeira, J. J. (2007) Estradiol sustained release from high affinity cyclodextrin hydrogels Eur. J. Pharm. Biopharm. 66, 55-62 (Pubitemid 46412967)
116. Rodriguez-Tenreiro, C., Diez-Bueno, L., Concheiro, A., Torres-Labandeira, J. J., and Alvarez-Lorenzo, C. (2007) Cyclodextrin/Carbopol micro-scale interpenetrating networks (ms-IPNs) for drug delivery J. Controlled Release 123, 56-66 (Pubitemid 47444387)
117. Yang, C. Y., Song, B. B., Ao, Y., Nowak, A. P., Abelowitz, R. B., Korsak, R. A., Havton, L. A., Deming, T. J., and Sofroniew, M. V. (2009) Biocompatibility of amphiphilic diblock copolypeptide hydrogels in the central nervous system Biomaterials 30, 2881-2898
118. Jiang, F. X., Yurke, B., Firestein, B. L., and Langrana, N. A. (2008) Neurite outgrowth on a DNA crosslinked hydrogel with tunable stiffnesses Ann. Biomed. Eng. 36, 1565-1579
119. Ramires, P. A., Miccoli, M. A., Panzarini, E., Dini, L., and Protopapa, C. (2005) In vitro and in vivo biocompatibility evaluation of a polyalkylimide hydrogel for soft tissue augmentation J. Biomed. Mater. Res., Part B 72B, 230-238
120. Skornia, S. L., Bledsoe, J. G., Kelso, B., and Kuntzwillits, R. (2007) Mechanical properties of layered poly (ethylene glycol) gels J. Appl. Biomater. Biomech. 5, 176-183 (Pubitemid 351495461)
121. Mahoney, M. J. and Anseth, K. S. (2006) Three-dimensional growth and function of neural tissue in degradable polyethylene glycol hydrogels Biomaterials 27, 2265-2274 (Pubitemid 41774537)
122. Krsko, P., McCann, T. E., Thach, T. T., Laabs, T. L., Geller, H. M., and Libera, M. R. (2009) Length-scale mediated adhesion and directed growth of neural cells by surface-patterned poly(ethylene glycol) hydrogels Biomaterials 30, 721-729
123. Koh, W. G., Revzin, A., and Pishko, M. V. (2002) Poly(ethylene glycol) hydrogel microstructures encapsulating living cells Langmuir 18, 2459-2462 (Pubitemid 35383811)
124. Salmaso, S., Sernenzato, A., Bersani, S., Matricardi, P., Rossi, F., and Caliceti, P. (2007) Cyclodextrin/PEG based hydrogels for multi-drug delivery Int. J. Pharm. 345, 42-50 (Pubitemid 350087539)
125. Pritchard, C. D., OShea, T. M., Siegwart, D. J., Calo, E., Anderson, D. G., Reynolds, F. M., Thomas, J. A., Slotkin, J. R., Woodard, E. J., and Langer, R. (2011) An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate Biomaterials 32, 587-597
126. Burdick, J. A., Ward, M., Liang, E., Young, M. J., and Langer, R. (2006) Stimulation of neurite outgrowth by neurotrophins delivered from degradable hydrogels Biomaterials 27, 452-459 (Pubitemid 41457248)
127. Piantino, J., Burdick, J. A., Goldberg, D., Langer, R., and Benowitz, L. I. (2006) An injectable, biodegradable hydrogel for trophic factor delivery enhances axonal rewiring and improves performance after spinal cord injury Exp. Neurol. 201, 359-367 (Pubitemid 44344229)
128. Metters, A. T., Anseth, K. S., and Bowman, C. N. (2000) Fundamental studies of a novel, biodegradable PEG-b-PLA hydrogel Polymer 41, 3993-4004 (Pubitemid 30116901)
129. Metters, A. T., Bowman, C. N., and Anseth, K. S. (2001) Verification of scaling laws for degrading PLA-b-PEG-b-PLA hydrogels AIChE J. 47, 1432-1437 (Pubitemid 36858870)
130. Li, J., Ni, X. P., and Leong, K. W. (2003) Injectable drug-delivery systems based on supramolecular hydrogels formed by poly(ethylene oxide) and alpha-cyclodextrin J. Biomed. Mater. Res., Part A 65A, 196-202 (Pubitemid 37521425)
131. Bakshi, A., Fisher, O., Dagci, T., Himes, B. T., Fischer, I., and Lowman, A. (2004) Mechanically engineered hydrogel scaffolds for axonal growth and angiogenesis after transplantation in spinal cord injury J. Neurosurg.: Spine 1, 322-329
132. Carone, T. W. and Hasenwinkel, J. M. (2006) Mechanical and morphological characterization of homogeneous and bilayered poly(2-hydroxyethyl methacrylate) scaffolds for use in CNS nerve regeneration J. Biomedical Mater. Res., Part B 78B, 274-282 (Pubitemid 44167729)
133. Piotrowicz, A. and Shoichet, M. S. (2006) Nerve guidance channels as drug delivery vehicles Biomaterials 27, 2018-2027 (Pubitemid 41759495)
134. Geever, L. M., Cooney, C. C., Lyons, J. G., Kennedy, J. E., Nugent, M. J. D., Devery, S., and Higginbotham, C. L. (2008) Characterisation and controlled drug release from novel drug-loaded hydrogels Eur. J. Pharm. Biopharm. 69, 1147-1159
135. Strappe, P. M., Hampton, D. W., Cachon-Gonzalez, B., Fawcett, J. W., and Lever, A. (2005) Delivery of a lentiviral vector in a Pluronic F127 gel to cells of the central nervous system Eur. J. Pharm. Biopharm. 61, 126-133 (Pubitemid 41427620)
136. Gander, B., Gurny, R., Doelker, E., and Peppas, N. A. (1989) Effect of Polymeric Network Structure on Drug Release from Cross-Linked Polyvinyl-Alcohol) Micromatrices Pharm. Res. 6, 578-584 (Pubitemid 19214422)
137. Bhattarai, N., Li, Z. S., Gunn, J., Leung, M., Cooper, A., Edmondson, D., Veiseh, O., Chen, M. H., Zhang, Y., Ellenbogen, R. G., and Zhang, M. Q. (2009) Natural-Synthetic Polyblend Nanofibers for Biomedical Applications Adv. Mater. 21, 2792-2797
138. Perale, G., Giordano, C., Bianco, F., Rossi, F., Tunesi, M., Daniele, F., Crivelli, F., Matteoli, M., and Masi, M. (2011) Hydrogel for Cell Housing in the Brain and in the Spinal Cord Int. J. Artif. Organs 34, 295-303
139. Leipzig, N. D. and Shoichet, M. S. (2009) The effect of substrate stiffness on adult neural stem cell behavior Biomaterials 30, 6867-6878
140. Leipzig, N. D., Wylie, R. G., Kim, H., and Shoichet, M. S. (2011) Differentiation of neural stem cells in three-dimensional growth factor-immobilized chitosan hydrogel scaffolds Biomaterials 32, 57-64
141. Hynes, S. R., McGregor, L. M., Rauch, M. F., and Lavik, E. B. (2007) Photopolymerized poly(ethylene glycol)/poly(l -lysine) hydrogels for the delivery of neural progenitor cells J. Biomater. Sci., Polym. Ed. 18, 1017-1030 (Pubitemid 47282467)
142. Perale, G., Veglianese, P., Rossi, F., Peviani, M., Santoro, M., Llupi, D., Micotti, E., Forloni, G., and Masi, M. (2011) In situ agar-carbomer polycondensation: a chemical approach to regenerative medicine Mater. Lett. 65, 1688-1692
143. Park, S. H., Chun, M. K., and Choi, H. K. (2008) Preparation of an extended-release matrix tablet using chitosan/Carbopol interpolymer complex Int. J. Pharm. 347, 39-44
144. Yu, L. M. Y., Kazazian, K., and Shoichet, M. S. (2007) Peptide surface modification of methacrylamide chitosan for neural tissue engineering applications J. Biomed. Mater. Res., Part A 82A, 243-255 (Pubitemid 46906512)
145. Wang, X. D., Hu, W., Cao, Y., Yao, J., Wu, J., and Gu, X. S. (2005) Dog sciatic nerve regeneration across a 30-mm defect bridged by a chitosan/PGA artificial nerve graft Brain 128, 1897-1910 (Pubitemid 41373662)
146. Shu, X. Z., Liu, Y. C., Palumbo, F. S., Lu, Y., and Prestwich, G. D. (2004) In situ crosslinkable hyaluronan hydrogels for tissue engineering Biomaterials 25, 1339-1348 (Pubitemid 37476210)
147. Mehrotra, S., Lynam, D., Maloney, R., Pawelec, K. M., Tuszynski, M. H., Lee, I., Chan, C., and Sakamoto, J. (2010) Time Controlled Protein Release from Layer-by-Layer Assembled Multilayer Functionalized Agarose Hydrogels Adv. Funct. Mater. 20, 247-258
148. DeForest, C. A., Sims, E. A., and Anseth, K. S. (2010) Peptide-Functionalized Click Hydrogels with Independently Tunable Mechanics and
149. de Jong, S. J., van Eerdenbrugh, B., van Nostrum, C. F., Kettenes-van de Bosch, J. J., and Hennink, W. E. (2001) Physically crosslinked dextran hydrogels by stereocomplex formation of lactic acid oligomers: degradation and protein release behavior J. Controlled Release 71, 261-275 (Pubitemid 32276046)
150. Kang, Y. M., Hwang, D. H., Kim, B. G., Go, D. H., and Park, K. D. (2010) Thermosensitive Polymer-based Hydrogel Mixed with the Anti-inflammatory Agent Minocycline Induces Axonal Regeneration in Hemisected Spinal Cord Macromol. Res. 18, 399-403
151. Bregonje, M. (2005) Patents: A unique source for scientific technical information in chemistry related industry? In World Patent Information (Blackman, M., Ed.), Vol. 27, issue 4, pp 309-315, Elsevier, San Diego, CA. (Pubitemid 41662461)
152. Eckenhoff, J. B., Theeuwes, F., and Deters, J. C. (1984) Dispenser comprising inner and outer walls functioning as cooperative unit, Alza Corporation. Patent US4663149.
153. Kliment, K., Vacik, J., Ott, Z., Majkus, V., Stoy, V., Stol, M., and Wichterle, O. (1966) Carrier for biologically active substances, Czechoslovak Academy of Science. Patent CA836532.
154. Giammona, G. and Mandracchia, D. (2004) Anionic hydrogel matrices with pH dependent modified release as drug carriers, Sigma Tau Industrie Farmaceutiche Riunite e Sigma Tau Industry Farmaceutiche Riunite. Patent WO2005/094792.
155. Deming, T. J., Sofroniew, M. V., Yang, C. Y., Song, B. B., and Ao, Y. (2009) Synthetic diblock copolypeptide hydrogels for use in the central nervous system, University of California. Patent WO2010/096572.
156. Kim, M. S., Lee, H. B., Lee, J. Y., Ahn, H. H., Lee, J. H., and Kim, K. S. (2008) Development of a tissue-engineered scaffold for nerve regeneration using a biocompatible and injectabe hydrogel, Korea Research Institute of Chemical Technology. Patent US2010/040660.
157. Daniele, F., Giordano, C., Masi, M., Perale, G., Rossi, F., and Tunesi, M. (2008) Hydrogel capable of containing and conveying cells, Politecnico di Milano. Patent WO2009/144569.
158. Cederna, P. S., Egeland, B. M., Abidian, M. R., Peramo, A., Urbancheck, M. G., Kipke, D. A., Richardson-Burns, S., and Martin, D. C. (2008) Hybrid bioelectrical interface device, University of Michigan. Patent WO2010/011386.
159. Hoke, A., Lim, S. H., Liu, X., and Mao, H. (2008) Biodegradable nerve guides, Johns Hopkins University. Patent WO2009/094225.
160. Gormans, J. R. (2006) Novel Regimens for Treating Diseases and Disorders, Bioassets Development. Patent US2010/0047235.
161. Sukuru, K. (2005) Lipophilic vehicle-based dual controlled release matrix system as capsule fill, Banner Pharmacaps. Patent WO2007/050724.
162. Sukuru, K. (2005) Hydrophilic vehicle-based dual controlled release matrix system as capsule fill, Banner Pharmacaps. Patent WO2007/050975.
163. Stein, S. and Sundaram, P. (2005) Detoxification depot for Alzheimers disease, Senicure. Patent WO2007/047967.
164. Lelkes, P. I., Li, M., Perets, A., Poblete, H., and Lazarovici, P. (2005) Three-dimensional ccaffolds for tissue engineering made by processing complex extracts of natural extracellular matrices, Drexel University. Patent WO2006/138718.
165. Sinko, P. J., Stein, S., and Lalloo, A. (2004) Controlled release hydrogels, Rutgers the State University of New Jersey. Patent WO2006/069344.
166. Tyagi, P., Chancellor, M. B., Li, Z., Chuang, Y. C., De Groat, W. C., Yoshimira, N., Fraser, M. O., and Huang, L. (2004) Use of lipid and hydrogel vehicles for treatment and drug delivery, University of Pittsburg. Patent WO2006/065234.
167. Oray, S., Majewska, A. K., Sur, M., and Teng, Y. (2004) Compositions and methods for enhancing structural and functional nervous system reorganization and recovery, Brigham & Womens Hospital, Massachusetts Institute of Technology. Patent WO2006/023530.
168. Romero-Ortega, M. I. and Galvan-Garcia, P. (2003) Biomimetic synthetic nerve implant casting device, Texas Scottish Rite Hospital. Patent US2007/100358.
169. Kramer, B. C. and Herzberg, U. (2008) Systemically and locally administered cells for neuropathic pain, Ethicon. Patent WO2010/071862.
170. Gilbert, R. J., Martin, B. C., Pap, M. M., and Minner, E. J. (2008) Novel hydrogel compositions and methods of using, Michigan Technological University. Patent US2010/112014.
171. Font, P. J., Del Olmo, B. M., Castro, F. M. B., Infante, M. A., Alonso, V. A. I., and Palomares, C. T. (2008) New biomaterial based on Whartons jelly from the human umbilical cord, Histocell. Patent WO2010/040865.
172. Gupta, D., Shoichet, M. S., and Tator, C. H. (2005) Blends of temperature sensitive and anionic polymers for drug delivery. Patent US2006/280797.
173. Pritchard, C. D., Langer, R., Reynolds, L. F., and Woodard, E. J. (2008) Spinal cord injury, inflammation, and immune disease: local controlled release of therapeutic agents, Invivo Therapeutics. Patent WO2010/036961.
174. Cauller, L. and Weiner, R. (2003) Microtransponder array for implant microtransponder, University of Texas. Patent US2009/198293.