A pilot study of poly(N-isopropylacrylamide)-g-polyethylene glycol and poly(N-isopropylacrylamide)-g-methylcellulose branched copolymers as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord: Laboratory investigation

Journal of Neurosurgery: Spine

Volumn 15, Issue 6, 2011, Pages 594-604

  Conova, Lauren ^a   Vernengo, Jennifer ^b   Jin, Ying ^c   Himes, B Timothy ^c,d   Neuhuber, Birgit ^c   Fischer, Itzhak ^c   Lowman, Anthony ^a  

^a Drexel University   (United States)

^b Rowan University   (United States)

^c DREXEL UNIVERSITY COLLEGE OF MEDICINE   (United States)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Biocompatibility; Cell transplantation; Growth factor; Hydrogel; Immune response; Spinal cord injury

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; POLY(N ISOPROPYLACRYLAMIDE); POLY(N ISOPROPYLACRYLAMIDE) G METHYLCELLULOSE; POLY(N ISOPROPYLACRYLAMIDE) G POLYETHYLENE GLYCOL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL SURVIVAL; CELL TRANSPLANTATION; CONTROLLED STUDY; DRUG DELIVERY SYSTEM; FEMALE; GLIA; HISTOPATHOLOGY; HYDROGEL; IMMUNE RESPONSE; IN VIVO STUDY; INFLAMMATION; NERVE FIBER GROWTH; NONHUMAN; RAT; SCAR; SPINAL CORD INJURY; TREATMENT OUTCOME;

ACRYLAMIDES; ANIMALS; AXONS; BRAIN-DERIVED NEUROTROPHIC FACTOR; CELL TRANSPLANTATION; CICATRIX; DISEASE MODELS, ANIMAL; DRUG DELIVERY SYSTEMS; FEMALE; GRAFT SURVIVAL; HYDROGELS; INJECTIONS, INTRALESIONAL; METHYLCELLULOSE; NERVE REGENERATION; NEUROGLIA; PILOT PROJECTS; POLYETHYLENE GLYCOLS; POLYMERS; RATS; RATS, SPRAGUE-DAWLEY; SPINAL CORD INJURIES; TISSUE SCAFFOLDS;

EID: 83055193711     PISSN: 15475654     EISSN: 15475646     Source Type: Journal    
DOI: 10.3171/2011.7.SPINE11194     Document Type: Article

References (52)

1. Aubert-Pouëssel A, Venier-Julienne MC, Clavreul A, Sergent M, Jollivet C, Montero-Menei CN, et al.: In vitro study of GDNF release from biodegradable PLGA microspheres. J Control Release 95:463-475, 2004
2. Benoit JP, Faisant N, Venier-Julienne MC, Menei P: Development of microspheres for neurological disorders: from basics to clinical applications. J Control Release 65:285-296, 2000 (Pubitemid 30122933)
3. Blight AR: Effects of silica on the outcome from experimental spinal cord injury: implication of macrophages in secondary tissue damage. Neuroscience 60:263-273, 1994
4. Bryant SJ, Davis-Arehart KA, Luo N, Shoemaker RK, Arthur JA, Anseth KS: Synthesis and characterization of photopolymerized multifunctional hydrogels: water-soluble poly(vinyl alcohol) and chondroitin sulfate macromers for chondrocyte encapsulation. Macromolecules 37:6726-6733, 2004
5. Burdick JA, Ward M, Liang E, Young MJ, Langer R: Stimulation of neurite outgrowth by neurotrophins delivered from degradable hydrogels. Biomaterials 27:452-459, 2006 (Pubitemid 41457248)
6. Chen Q, Zhou L, Shine HD: Expression of neurotrophin-3 promotes axonal plasticity in the acute but not chronic injured spinal cord. J Neurotrauma 23:1254-1260, 2006 (Pubitemid 44681480)
7. Comolli N, Neuhuber B, Fischer I, Lowman A: In vitro analysis of PNIPAAm-PEG, a novel, injectable scaffold for spinal cord repair. Acta Biomater 5:1046-1055, 2009
8. Dhar S, Radulescu D, Gharibjanian NA, Hayes DJ, Evans GRD: Regulated nerve growth factor delivery on novel polymers by hNGF-EcR-293-TK cells. J Reconstr Microsurg 22:A028, 2006 (Abstract)
9. Flanagan LA, Ju YE, Marg B, Osterfield M, Janmey PA: Neurite branching on deformable substrates. Neuroreport 13:2411-2415, 2002 (Pubitemid 36143534)
10. Gehrmann J, Matsumoto Y, Kreutzberg GW: Microglia: intrinsic immuneffector cell of the brain. Brain Res Brain Res Rev 20:269-287, 1995
11. Gupta D, Tator CH, Shoichet MS: Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials 27:2370-2379, 2006 (Pubitemid 41821815)
12. Himes BT, Goldberger ME, Tessler A: Grafts of fetal central nervous system tissue rescue axotomized Clarke's nucleus neurons in adult and neonatal operates. J Comp Neurol 339:117-131, 1994 (Pubitemid 23361787)
13. Himes BT, Liu Y, Solowska JM, Snyder EY, Fischer I, Tessler A: Transplants of cells genetically modified to express neurotrophin-3 rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats. J Neurosci Res 65:549-564, 2001 (Pubitemid 32847148)
14. Himes BT, Neuhuber B, Coleman C, Kushner R, Swanger SA, Kopen GC, et al.: Recovery of function following grafting of human bone marrow-derived stromal cells into the injured spinal cord. Neurorehabil Neural Repair 20:278-296, 2006
15. Hirschberg DL, Yoles E, Belkin M, Schwartz M: Inflammation after axonal injury has conflicting consequences for recovery of function: rescue of spared axons is impaired but regeneration is supported. J Neuroimmunol 50:9-16, 1994 (Pubitemid 24043065)
16. Horn KP, Busch SA, Hawthorne AL, van Rooijen N, Silver J: Another barrier to regeneration in the CNS: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. J Neurosci 28:9330-9341, 2008
17. Ibarra A, Correa D, Willms K, Merchant MT, Guizar-Sahagún G, Grijalva I, et al.: Effects of cyclosporin-A on immune response, tissue protection and motor function of rats subjected to spinal cord injury. Brain Res 979:165-178, 2003 (Pubitemid 36792167)
18. Ibarra A, Diaz-Ruiz A: Protective effect of cyclosporin-A in spinal cord injury: an overview. Curr Med Chem 13:2703-2710, 2006 (Pubitemid 44364147)
19. Jain A, Kim YT, McKeon RJ, Bellamkonda RV: In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury. Biomaterials 27:497-504, 2006 (Pubitemid 41457252)
20. Jin Y, Fischer I, Tessler A, Houle JD: Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury. Exp Neurol 177:265-275, 2002 (Pubitemid 35356839)
21. Joosten EA: Corticospinal tract regrowth. Prog Neurobiol 53:1-25, 1997
22. Kawaja MD, Fagan AM, Firestein BL, Gage FH: Intracerebral grafting of cultured autologous skin fibroblasts into the rat striatum: an assessment of graft size and ultrastructure. J Comp Neurol 307:695-706, 1991
23. Kim S, Healy KE: Synthesis and characterization of injectablepoly(N- isopropylacrylamide-co-acrylic acid) hydrogels with proteolytically degradable cross-links. Biomacromolecules 4:1214-1223, 2003 (Pubitemid 37184633)
24. Lavik E, Teng YD, Snyder E, Langer R: Seeding neural stem cells on scaffolds of PGA, PLA, and their copolymers. Methods Mol Biol 198:89-97, 2002
25. Lepore AC, Fischer I: Lineage-restricted neural precursors survive, migrate, and differentiate following transplantation into the injured adult spinal cord. Exp Neurol 194:230-242, 2005 (Pubitemid 40719758)
26. Levenberg S, Burdick JA, Kraehenbuehl T, Langer R: Neurotrophin-induced differentiation of human embryonic stem cells on three-dimensional polymeric scaffolds. Tissue Eng 11:506-512, 2005 (Pubitemid 40632566)
27. Liu Y, Himes BT, Tryon B, Moul J, Chow SY, Jin H, et al.: Intraspinal grafting of fibroblasts genetically modified by recombinant adenoviruses. Neuroreport 9:1075-1079, 1998 (Pubitemid 28266625)
28. Liu Y, Kim D, Himes BT, Chow SY, Schallert T, Murray M, et al.: Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function. J Neurosci 19:4370-4387, 1999 (Pubitemid 29241090)
29. Lu J, Féron F, Mackay-Sim A, Waite PME: Olfactory ensheathing cells promote locomotor recovery after delayed transplantation into transected spinal cord. Brain 125:14-21, 2002 (Pubitemid 34084033)
30. Madigan NN, McMahon S, O'Brien T, Yaszemski MJ, Windebank AJ: Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds. Respir Physiol Neurobiol 169:183-199, 2009
31. Maquet V, Jerome R: Design of macroporous biodegradable polymer scaffolds for cell transplantation. Mater Sci Forum 250:15-42, 1997 (Pubitemid 127565052)
32. McMahon SS, Albermann S, Rooney GE, Moran C, Hynes J, Garcia Y, et al.: Effect of cyclosporin A on functional recovery in the spinal cord following contusion injury. J Anat 215:267-279, 2009
33. Mitsui T, Shumsky JS, Lepore AC, Murray M, Fischer I: Transplantation of neuronal and glial restricted precursors into contused spinal cord improves bladder and motor functions, decreases thermal hypersensitivity, and modifies intraspinal circuitry. J Neurosci 25:9624-9636, 2005 (Pubitemid 41510903)
34. Murray M, Fischer I, Smeraski C, Tessler A, Giszter S: Towards a definition of recovery of function. J Neurotrauma 21:405-413, 2004 (Pubitemid 38509424)
35. Nomura H, Tator CH, Shoichet MS: Bioengineered strategies for spinal cord repair. J Neurotrauma 23:496-507, 2006 (Pubitemid 43726324)
36. Novikov L, Novikova L, Kellerth JO: Brain-derived neurotrophic factor promotes axonal regeneration and long-term survival of adult rat spinal motoneurons in vivo. Neuroscience 79:765-774, 1997 (Pubitemid 27292673)
37. Oudega M, Gautier SE, Chapon P, Fragoso M, Bates ML, Parel JM, et al.: Axonal regeneration into Schwann cell grafts within resorbable poly(alpha-hydroxyacid) guidance channels in the adult rat spinal cord. Biomaterials 22:1125-1136, 2001 (Pubitemid 32229937)
38. Oudega M, Hagg T: Neurotrophins promote regeneration of sensory axons in the adult rat spinal cord. Brain Res 818:431-438, 1999 (Pubitemid 29229957)
39. Patist CM, Mulder MB, Gautier SE, Maquet V, Jérôme R, Oudega M: Freeze-dried poly(D,L-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord. Biomaterials 25:1569-1582, 2004 (Pubitemid 38091536)
40. Prewitt CM, Niesman IR, Kane CJ, Houlé JD: Activated macrophage/microglial cells can promote the regeneration of sensory axons into the injured spinal cord. Exp Neurol 148:433-443, 1997 (Pubitemid 28068839)
41. Rolls A, Shechter R, London A, Segev Y, Jacob-Hirsch J, Amariglio N, et al.: Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Med 5:e171, 2008
42. Schwartz M, Lazarov-Spiegler O, Rapalino O, Agranov I, Velan G, Hadani M: Potential repair of rat spinal cord injuries using stimulated homologous macrophages. Neurosurgery 44:1041-1046, 1999 (Pubitemid 29202864)
43. Shibayama M, Hattori S, Himes BT, Murray M, Tessler A: Neurotrophin-3 prevents death of axotomized Clarke's nucleus neurons in adult rat. J Comp Neurol 390:102-111, 1998 (Pubitemid 28083649)
44. Stabenfeldt SE, García AJ, LaPlaca MC: Thermoreversible laminin-functionalized hydrogel for neural tissue engineering. J Biomed Mater Res A 77:718-725, 2006 (Pubitemid 47233553)
45. Stichel CC, Müller HW: Experimental strategies to promote axonal regeneration after traumatic central nervous system injury. Prog Neurobiol 56:119-148, 1998 (Pubitemid 28432562)
46. Sugar O, Gerard RW: Spinal cord regeneration in the rat. J Neurophysiol 3:1-19, 1940
47. Taylor L, Jones L, Tuszynski MH, Blesch A: Neurotrophin-3 gradients established by lentiviral gene delivery promote short-distance axonal bridging beyond cellular grafts in the injured spinal cord. J Neurosci 26:9713-9721, 2006 (Pubitemid 44427710)
48. Tessler A, Fischer I, Giszter S, Himes BT, Miya D, Mori F, et al.: Embryonic spinal cord transplants enhance locomotor performance in spinalized newborn rats. Adv Neurol 72:291-303, 1997
49. Tessler A, Himes BT, Houle J, Reier PJ: Regeneration of adult dorsal root axons into transplants of embryonic spinal cord. J Comp Neurol 270:537-548, 1988
50. Tuszynski MH, Grill R, Jones LL, Brant A, Blesch A, Löw K, et al.: NT-3 gene delivery elicits growth of chronically injured corticospinal axons and modestly improves functional deficits after chronic scar resection. Exp Neurol 181:47-56, 2003 (Pubitemid 36438675)
51. Vernengo J, Fussell GW, Smith NG, Lowman AM: Evaluation of novel injectable hydrogels for nucleus pulposus replacement. J Biomed Mater Res B Appl Biomater 84:64-69, 2008
52. Wagner FC Jr, Van Gilder JC, Dohrmann GJ: The development of intramedullary cavitation following spinal cord injury: an experimental pathological study. Paraplegia 14:245-250, 1977 (Pubitemid 8051110)