Polymers in Medicine

Polim. Med.
Scopus CiteScore: 3.5 (CiteScore Tracker 3.6)
Index Copernicus (ICV 2023) – 121.14
MEiN – 70
ISSN 0370-0747 (print)
ISSN 2451-2699 (online) 
Periodicity – biannual

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Polymers in Medicine

2013, vol. 43, nr 2, April-June, p. 59–80

Publication type: review article

Language: Polish

Strategie inżynierii biomateriałów dla regeneracji rdzenia kręgowego: aktualny stan wiedzy

Biomaterials Engineering Strategies for Spinal Cord Regeneration: State of the Art

Anna Lis1,, Dariusz Szarek2,, Dariusz Szarek3,, Jadwiga Laska1,

1 Wydział Inżynierii Materiałowej i Ceramiki, Katedra Biomateriałów, Akademia Górniczo-Hutnicza w Krakowie

2 Klinika Neurochirurgii, Uniwersytecki Szpital Kliniczny we Wrocławiu

3 Katedra Neurochirurgii, Uniwersytet Medyczny im. Piastów Śląskich we Wrocławiu

Streszczenie

Urazowe uszkodzenia rdzenia kręgowego stanowią bardzo poważne obciążenie dla organizmu osób poszkodowanych i są tym dotkliwsze, ponieważ najczęściej dotyczą przede wszystkim ludzi młodych. Spowodowane nimi problemy fizyczne, emocjonalne i ekonomiczne z reguły istotnie ograniczają funkcjonowanie pacjentów i stanowią obciążenie dla społeczeństwa. Rdzeń kręgowy charakteryzuje się niemal brakiem możliwości spontanicznej i funkcjonalnej regeneracji, stąd jego uszkodzenie powoduje poważne i często trwałe kalectwo. Patofizjologia uszkodzenia rdzenia kręgowego jest wynikiem następujących po sobie dwóch zjawisk; urazu pierwotnego oraz wtórnego. Po uszkodzeniach pierwotnych w wyniku urazu mechanicznego następują zmiany patologiczne o podłożu biochemicznym narastające kaskadowo po urazie, które nawzajem się wzmacniają i powodują dalszą destrukcję rdzenia kręgowego. Następuje kaskada procesów patologicznych w tym krwotok, obrzęk, nekroza neuronów, fragmentacja i demielinizacja aksonów i ostatecznie tworzenie się cysty. Ponadto urazy rdzenia kręgowego mogą spowodować natychmiastową śmierć komórek nerwowych oraz zakłócić dopływ krwi do miejsca uszkodzenia. Ważną różnicą pomiędzy obwodowym i centralnym układem nerwowym jest to, że podczas urazu w rdzeniu kręgowym ulegają zniszczeniu zarówno ciała komórek nerwowych i aksony dróg rdzeniowych, podczas gdy w obwodowym układzie nerwowym tylko aksony podlegają uszkodzeniu. W obrębie rdzenia kręgowego jednym z głównych czynników hamujących regenerację jest tworzenie się blizny glejowej. Rozprzestrzeniające się na powierzchni uszkodzenia gęsto upakowane astrocyty hamują skutecznie wzrost aksonów poprzez blokadę wzrostu. Blizna składająca się głównie z nadaktywnych astrocytów i fibroblastów wraz z obecnymi w niej związkami inhibitującymi wzrost aksonów, takimi jak proteoglikany (pochodzące z rozpadu uszkodzonych komórek nerwowych), stanowi barierę fizyko-chemiczną dla efektywnej regeneracji aksonów. Obecny postęp naukowy w medycynie, biologii oraz inżynierii biomateriałów, a w szczególności w dziedzinach neurochirurgii, hodowli komórkowej i inżynierii tkankowej, otwiera możliwość dla rozwoju nowych terapii wspomagających leczenie skutków urazowych uszkodzeń rdzenia kręgowego i zapobiegających dalszym procesom neurodegeneracyjnym. Najbardziej obiecujące wyniki, jak dotąd, uzyskuje się przy zastosowaniu odpowiednio zaprojektowanych konstrukcji polimerowych stanowiących rusztowanie dla regenerujących aksonów, w połączeniu z systemem dostarczania leków lub linii komórek terapeutycznych oraz czynników neurotroficznych. W niniejszym artykule przeglądowym opisano wybrane zastosowania biomateriałów w regeneracji urazowych uszkodzeń rdzenia kręgowego. Na wstępie opisana została podstawowa budowa anatomiczna rdzenia kręgowego. Następnie porównane zostały mechanizmy uszkodzeń i neuroregeneracji w obwodowym i centralnym układzie nerwowym. Patofizjologia uszkodzeń rdzenia kręgowego, odniesiona została do bieżących strategii inżynierii biomateriałowej w eksperymentalnych terapiach wspomagających neuroregenerację. W podsumowaniu zwrócono uwagę na obiecujące interdyscyplinarne strategie terapeutyczne, mające na celu regenerację rdzenia kręgowego.

Abstract

Traumatic spinal cord injuries are very serious burden for the organism of affected human population, and are more critical because mostly touching the young cluster of population. Physical, emotional and economic problems caused by traumatic spinal cord injuries as a general rule significantly limit the individual patient functionality and are burden for the society. The spinal cord has considerable lack of ability for spontaneous and functional regeneration, hence the spinal cord injury cause a solemn and frequently permanent disabilities. The pathophysiology of spinal cord injury is the results of sequential two phenomena, primary physical and biochemical secondary mechanisms of injury. After physical injury, the spinal cord undergoes a sequential progression in biochemical pathologic deviations increasing after injury, that are mutually deteriorating and cause further damage in the spinal cord. Consequently series of pathological processes lead to haemorrhage, oedema, neuronal necrosis, axonal fragmentation, demyelination of the remaining axons, and formation of ultimately cyst. Furthermore spinal cord injuries can immediately result in neural cells death and cause disruption of the blood supply to the site of the injury. The most important difference between peripheral and central nervous system is the fact that in the spinal cord the neuronal cell bodies are damaged, while in the peripheral nervous system only axons are injured. In the surroundings of the spinal cord, one of the major factors hampering regeneration is the glial scar expansion. The spreading of densely packed astrocytes on the site of injuries effectively inhibit axon growth through the nerve grow blocking. Glial scar, which consists mainly of overactive astrocytes and fibroblasts, as well as the presence of growth-inhibitor molecules such as chondroitin sulphate proteoglycans (derived from the breakdown of damaged nerve cells) form a physicochemical barrier for effective regenerating axons. The recent scientific progress in medicine, biology and biomaterials engineering, and predominantly in the fields of neurosurgery, cell culture and tissue engineering, creates the opportunity for the development of new therapies, which support healing of the effects of traumatic spinal cord injuries and prevent further neurodegenerative processes. The most promising effects so far have been obtained using well-designed polymer scaffold as structural support for axon regeneration combined with drug delivery system or therapeutic cell line and neurotrophic factors. This review article focuses on the application of selected biomaterials for the regeneration of traumatic spinal cord injuries. First, the basic anatomical structure of the spinal cord has been described. Then the injury and neurodegenerative mechanisms within the peripheral and central nervous system have been compared. The pathophysiology of the spinal cord damage has been referred to the current strategy of biomaterials engineering in experimental therapies supporting neuroregeneration processes. In the summary, the promising interdisciplinary therapeutic strategies aimed at the regeneration of the spinal cord have been highlighted.

Słowa kluczowe

biomateriały, centralny układ nerwowy, rdzeń kręgowy, regeneracja nerwów

Key words

biomaterials, central nervous system, spinal cord, nerve regeneration

References (172)

  1. Batchelor P.E., Howells D.W.: CNS regeneration: clinical possibility or basic science fantasy? Review, Journal of Clinical Neuroscience, (2003), 10 (5), 523–534.
  2. Dietz V., Curt A.: Neurological aspects of spinal-cord repair: promises and challenges. Review, Lancet Neurol, (2006), 5, 688–694.
  3. Bergman B.S.: Regeneration in the spinal cord. Current Opinion in Neurobiology, (1998), 8, 800–807.
  4. Gruener G., Biller J.: Spinal Cord Anatomy, Localization, and Overview of Spinal Cord Syndromes. Continuum: Lifelong Learning Neurol, (2008), 14(3), 11–35.
  5. Craven J.: Spinal Cord – Anatomy, Anesthesia and Intensive Care Medicine. The Medicine Publishing Company (2004) 144–146.
  6. Burt A.A.: The epidemiology, natural history and prognosis of spinal cord injury. Mini-Symposium: Spinal Trauma, Current Orthopaedics, (2004), 18, 26–32.
  7. Taoka Y., Okajama K.: Spinal Cord Injury in the Rat. Progress in Neurobiology, (1998), 56, 341–358.
  8. O’Connor P.: Injury to the spinal cord in motor vehicle traffic crashes. Accident Analysis and Prevention, (2002), 34, 477–485.
  9. Pickett G.E., Campos-Benitez M., Keller J., L., Duggal N.: Epidemiology of Traumatic Spinal Cord Injury in Canada, Spine, (2006), 31(7), 799–805.
  10. Fehlings M.G., Baptiste D.C.: Current status of clinical trials for acute spinal cord injury. Injury International Journal of the Care of the Injured, (2005), 36, 113–122.
  11. Finnerup N.B., Baastrup C., Jensen T.S.: Neuropathic pain following spinal cord injury pain: mechanisms and treatment. Scandinavian Journal of Pain, (2009), 1, 3–11.
  12. Chang W.L., Ke D., S., Cheng T., J.: Lateral Medullary Infraction Presenting as Brown-Sequard Syndrome like Manifestation. A case Report and Literature Review, Acta Neurologia Taiwanica, (2010), 18, 204–207.
  13. Sathirapanya P., Taweelarp A., Sae Heng S., Riabroi K.: Case Report Brown-Sequard syndrome from cervical disc herniation, a case report and review of literature. Neurology Asia, (2007), 38; 65–67.
  14. Garcia-Manzanares M.D., Belda-Sanchis J.L., Giner-Pascual M., Miguel-Leon I., Delgado-Calvo M., Alio y Sanz J.L.: Brown-Sequard syndrome associated with Horner’s syndrome after penetrating trauma at the cervicomedullary junction. Case Report, Spinal Cord, (2000), 38, 705–707.
  15. Zubair M., Ravidran T., Chan C.Y.W., Saw L.B., Kwan M.K.: Acute Brown-Sequard syndrome following brachial plexus avulsion injury. A report of two cases. Hong Kong Journal of Emergency Medicine, (2011), 18, 347–351.
  16. Newey M.L., Sen P., K., Fraser R., D.: The long-term outcome after central cord syndrome. The Journal of Bone and Joint Surgery, (2000), 82, 851–855.
  17. Harrop J.S., Sharan A., Rafliff J., Central cord injury; pathophysiology, management, and outcomes. The Spine Journal, (2006), 6, 198–206.
  18. Omac O.K., Karadeniz M., Kesikburun S., Yasar E., Yilmaz B., Alaca R.: Posterior Cord Syndrome Associated with Dural Ectasia, Arachnoid Cyst and Spinal Cord Atrophy in Patient with Marfan Syndrome: Case Report, Journal of Physical Medicine and Rehabilitation Sciences, (2010), 13, 069–071.
  19. Bennet D.S., Alo K., M., Oakley J, C., A., Feler C.A.: Spinal Cord Stimulation for Complex Regional Pain Syndrome (RSD): a Retrospective Multicenter Experience from 1995–1998 of 101 Patients. Neuromodulation, (1999), 2(3), 2002–210.
  20. Ptaszyńska-Sarosiek I., Niemcunowicz-Janica A., Janica J.: Urazy kręgosłupa z uszkodzeniem rdzenia kręgowego – poglądy reprezentowane przez neurologów (Spinal cord injuries – opinions represented by neurologists). Archiwum Medycyny Sądowej i Kryminologii (2007), LVII, 294–297.
  21. Hall E.D., Wolf D.L.: A pharmacological analysis of the pathological mechanisms of post traumatic spinal cord ischemia. Journal of Neurosurgery (1986), 64, 951–961.
  22. Dumont R.J., Okonkwo D.O., Verma S., Hulbert R.J., Boulas P.T., Ellegala D.B., Dumont A.S.; Acute Spinal Cord Injury. Part I: Pathophysiologic Mechanisms, Clinical Neuropharmacology (2001), 24 (5), 254–264.
  23. Hall E.D., Braughler J.M.: Glucocorticoid mechanisms in acute spinal cord injury: a review and therapheuthic rationale. Surgical Neurology (1982), 18, 320–327.
  24. Fehlings M.G., Nguyen D.H.: Immunoglobulin G: a potential treatment to attenuate neuroinflamation following spinal cord injury. Journal of Clinical Immunology (2010), 1, 109–112.
  25. Dumont R.J., Verma S., Onkowo D.O., Hulbert R.J., Boulos P.T., Ellegala D.B., Dumont A.S.: Acute Spinal Cord Injury, Part II: Contemporary Pharmacotheraphy. Clinical Neuropharmacology (2001), 24 (5), 265–279.
  26. Schnell L., Feam S, Klassen H., Schwab M.E., Perry V.H.: Acute inflammatory responses to mechanical lessions in the CNS: Differences between brain and spinal cord. European Journal of Neuroscience (1999), 11, 3648–3658.
  27. Ray S.K., Dixon C.E., Banik N.L.: Molecular mechanism in the pathogenesis of traumatic brain injury. Histology and Histopathology (2002), 17, 1137–1152.
  28. Rossingnal S., Schwab M., Schwartz M., Fehlings G.: Spinal Cord Injury: Time to Move? Journal of Neuroscience (2007), 27, 11782–11792.
  29. Hulsebosch C.E.: Recent advance in pathophysiology and treatment of spinal cord injury Advances in Physiology Education (2002), 26, 238–255.
  30. Tator C.H., Mc Cormick P.C., Piepmeier J.M., Benzel E.C., Young W.: Biology of neurological recovery and functional restoration after spinal cord injury. Journal of Neurosurgery (1998), 42, 696–708.
  31. Tator C.H.: Strategies for recovery and regeneration after brain and spinal cord injury. Injury Prevention (2002), 8, 33–36.
  32. Schwab M.E., Bartholdi D.: Degeneration and regeneration of axons in the lesioned spinal cord. Physiological Reviews (1996), 76, 319–370.
  33. Seddon H.J., Classification of nerve injuries. Brit med J. (1942)/II., 237–239.
  34. Sunderland S.: Nerve and Nerve Injuries. Edinburg: Churchill-Livingstone (1978).
  35. Lee S.K., Wolfe S.W.: Peripheral Nerve Injury and Repair. Journal of the American Academy of Orthopaedic Surgeons, (2000), 8(4), 243–252.
  36. Waller A.: Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produces thereby in the structure of their primitive fibers. Phil Transact Royal Soc London, (1850), 140, 423–429.
  37. Lee S.K., Wolfe S.W., Peripheral Nerve Injury Repair Journal of American Academy of Orthopaedic Surgeons (2000), 8, 243–252.
  38. Hoke A.: Mechanisms of Disease: what factors limit the success of peripheral nerve regeneration in humans? Nature Clinical Practice, Neurology (2006) 2(8), 448–454.
  39. Belkas J.S., Schoichet M.S., Midha R.: Peripheral nerve regeneration through guidance tubes. Neurological Research (2004), 26, 1–10.
  40. Hall S.: The response to injury in the peripheral nervous system – review. The Journal of Bone and Joint Surgery (2005), 8(10), 1309–1319.
  41. Burnett M.G., Zager E.L.: Pathophysiology of peripheral nerve injury: a brief review. Neurosurgery Focus (2004), 16, 5, 1–7.
  42. Deumens R., Bozkut A., Meek M.F., Marcus M.A.E., Joosten E.A.J., Weis J., Brook G.A.: Repairing injured peripheral nerves: Bridging the gap. Progress in Neurobiology (2010), 92, 245–276.
  43. Priestley J.V., Ramer M.S., King V.R., McMahon S.B., Brown R.A.: Stimulating regeneration in the damaged spinal cord. Journal of Physiology – Paris, (2002), 96, 123–133.
  44. Reier P.J.: Cellular Transplantation Strategies for Spinal Cord Injury and Translational Neurobiology. The Journal of the American Society for Experimental Neuro Therapeutics, (2004), 1, 424–451.
  45. Horner P.J., Gage F.H.: Regenerating the damaged central nervous system – Review article. Nature, (2000), 407, 963–970.
  46. Schwab J.M., Brechtel K., Mueller Ch.-A., Failli V., Kaps H.-P., Tuli S.K., Schluesener H.J.: Experimental strategies to promote spinal cord regeneration – an integrative perspective. Progress in Neurobiology (2006) 91–116.
  47. Abu-Rub M., McMahon S., Zeugolis D.I., Windebank A., Pandit A.: Spinal cord injury in vitro: modelling axon growth inhibition, Drug Discovery Today, 2010, (15), 438–443.
  48. Deumens R., Koopmans G.C., Joosten E.A.J.: Regeneration of descending axon tracts after spinal cord injury. Progress in Neurobilogy, (2005) 57–89.
  49. Kang K. N, Kim D.Y., Yoon S.M., Lee J.Y., Lee B.N., Kwon J.S., H. Seo H.W., Lee I.W., Shin H.C., Kim Y.M., Kim H.S., Kim J.H., Min B.H., Lee H.B., Kim M.S.: Tissue engineered regeneration of completely transected spinal cord using human mesenchymal stem cells. Biomaterials (2012), 33, 4828–4835.
  50. Willerth S., Sakiyama-Elbert S.E.: Cell therapy for spinal cord regeneration. Advanced Drug Delivery Reviews, (2008), 60, 263–276.
  51. Lu P., Jones L.L., Tuszynski M.H.: Axon regeneration through scars and into sites of chronic spinal cord injury. Experimental Neurology, (2007), 203, 8–21.
  52. Novikova L.N., Lobov S., Wiberg M., Novikov L.N.: Efficacy of olfactory ensheathing cells to support regeneration after spinal cord injury is influenced by method of culture preparation. Experimental Neurology, (2011), 299, 132–142.
  53. Mann C.M., Kwon B.K.: An Update on the Pathophysiology of Acute Spinal Cord Injury. Seminars in Spine Surgery, (2007), 19, 272–279.
  54. Profyris C., Cheema S.S., Zang D.W., Azari M.F., Boyle K., Petratos S.: Degenerative and regenerative mechanisms governing spinal cord injury – Review. Neurobiology of Disease, (2004), 15, 415–436.
  55. Bauchet L., Lonjon N., Perrin F.E., Gilbert C., Privat A., Fattal C.: Strategies for spinal cord repair after injury: A review of the literature and information. Annals of Physical and Rehabilitation Medicine, (2009), 52, 330–351.
  56. Wilcox J.T., Cadotte D., Fehlings M.G.: Spinal cord clinical trials and the role for bioengineering – Review. Neuroscience Letters, (2012), 519, 93–102.
  57. He J. Wang X.M., Spector M., Cui F.Z.: Scaffolds for central nervous system tissue engineering. Frontier of Material Science (2012), 6(1), 1–25.
  58. Lu P., Jones L.L., Tuszynski M.H.: Axon regeneration through scar and into site of chronic spinal cord injury. Experimental Neurology (2007), 203, 8–21.
  59. Madigan N.N., McMahon S., O’Brien T., Yaszemski M.J., Windebank A.J.: Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds – Frontiers Review. Respiratory Physiology & Neurobiology, (2009), 169, 183–199.
  60. Tabesh H., Amoabediny Gh., Nik N.S., Heydari M., Yosefifard M., Ranaei Siadat S.O., Mottaghy K.: The role of biodegradable engineered scaffolds seeded with Schwann cells for spinal cord regeneration. Neurochemistry International, (2009), 54, 73–83.
  61. Samadikuchaksaraei A.: An overview of tissue engineering approaches for management of spinal cord injuries – Review. Journal of NeuroEgineering and Rehabilitation, (2007), 4:15.
  62. Stichel C.C., Werner Muller H.: Experimental strategies to promote axonal regeneration after traumatic central nervous system injury. Progress in Neurobiology, (1998), 56, 119–148.
  63. Geller H.M., Fawcett J.W.: Building a Bridge: Engineering Spinal Cord Repair – Review. Experimental Neurology, (2002) 174, 125–136.
  64. Onuki Y., Bhardwaj U., Papadimitrakopoulos F., Burgens D.J.: A review of the Biocompatibility of Implantable Devices: Current Challenges to Overcome Foreign Body Response. Journal Diabets Science and Technology (2008), 2(6), 1003– 1015.
  65. Błażewicz S.: Nazewnictwo i definicje dotyczące problematyki biomateriałów, w: Biocybernetyka i inżynieria biomedyczna 2000, tom 4 – Biomateriały, pod red. S. Błażewicza i L. Stocha, AOW EXIT (2003) 597–607.
  66. Marciniak J.: Biomateriały, Wydawnictwo Politechniki Śląskiej, Gliwice (2002), Rozdział I.
  67. Bhat S., Kumar A.: Biomaterials in Regenerative Medicine. Journal of Postgraduate Medicine Education Research (2012), 46(2), 81–89.
  68. Patel N.R., Gohil P.P.: A review on Biomaterials: Scope, Applications & Human Anatomy Significance, International Journal of Emerging Technology and Advanced engineering (2012), 2(4), 2450–2459.
  69. Gogolewski S.: Produkty degradacji, w: Biocybernetyka i inżynieria biomedyczna 2000, tom 4 – Biomateriały, pod red. S. Błażewicza i L. Stocha, AOW EXIT (2003) 257–330.
  70. Pielka S., Paluch D., Staniszewska-Kuś J., Solski L., Lewandowska-Szumieł M.: Badania biozgodności materiałów implantacyjnych, w: Biocybernetyka i inżynieria biomedyczna 2000, tom 4 – Biomateriały, pod red. S. Błażewicza i L. Stocha, AOW EXIT (2003) 437–439.
  71. Będziński R., Pezowicz C., Szust A.: Biomechanika kręgosłupa, w: Biocybernetyka i Inżynieria Biomedyczna, tom 5 – Biomechanika, pod redakcją R. Będzińskiego, K. Kędziora, J. Kiwerskiego, A. Moreckiego, K. Skalskiego, A. Walla oraz A. Wita, AOW EXIT (2004) 113–158.
  72. Li Y., Yang S.-T.: Effects of Three-dimensional Scaffolds on Cell Organization and Tissue Development. Biotechnol. Bioprocess Eng., (2001), 6, 311–325.
  73. Hou Q., Gijpma D.W., Feijen J.: Preparation of Interconnected Highly Porous Polymeric Structures by a Replication and Freeze-Drying Process.
  74. Liu W., Themopoulos S., Xia Y.: Electrospun nanofibers for regenerative medicine. Advanced Health Materials (2012), 1(1), 10–25.
  75. Martins A., Aranjo J.V., Reis R.L., Neves N.M.: Electrospun nanostructured scaffold for tissue engineering applications. Nanomedicine (2007), 2(6), 929–942.
  76. Sill T.J., von Recum H.A.: Electrospinning: applications in drug delivery and tissue engineering. Biomaterials (2008), 29(13), 1989–2006.
  77. Kumbar S.G., James R., Nukavarapu S.P., Laurecin C.T.: Electrospun nanofiber scaffolds engineering soft tissues. Biomedical Materials (2008), 3, 3.
  78. Zhang Y.Z., Su B., Venugopal J., Ramakrishna S., Lim C.T.: Biomimetic and bioactive nanofibers scaffolds from electrospun composite nanofibers. International Journal of Nanomedicine (2007), 2(4), 623–638.
  79. Schmalenberg K.E., Uhrich K.E., Micropatterned polymer substrates control alignment of proliferation Schwann cells to direct neuronal regeneration. Biomaterials (2005), 26, 1423–1430.
  80. Thomas A.M., Kubilius M.B., Holland S.J., Seidlits S.K., Boehler R.M., Anderson A.J., Cummings B.J., Shea L.D.: Channel density and porosity of degradable bridging scaffolds on axon growth after spinal cord. Biomaterials (2013), 34, 2213–2220.
  81. Khare A.R., Peppas N.A.: Swelling/deswelling of ionic copolymer gels. Biomaterials (1995) 16, 559–567.
  82. Van Tomme S.R., Storm G., Hennik W.E.: In situ gelling hydrogels for pharmaceutical and biomedical applications. International Journal of Pharmaceuthics (2008), 355, 1–18.
  83. Baier R.E.: Surface behaviour of biomaterials: The thetha surface for biocompatibility. Journal of Material Science: Materials in Medicine (2006), 17, 1057–1062.
  84. Roach P., Parker T., Gadegaard N., Alexander M.R.: Surface strategies for control of neuronal cell adhesion: A review. Surface Science Reports (2010), 65, 145–173.
  85. Gogolewski S.: Metody przetwarzania polimerów na wyroby medyczne - Sterylizacja wyrobów polimerowych, w: Biocybernetyka i inżynieria biomedyczna 2000, tom 4 – Biomateriały, pod red. S. Błażewicza i L. Stocha, AOW EXIT (2003) 286– 287.
  86. Ratajska M., Boryniec S.: Physical and chemical aspects of biodegradation of natural polymers. Reactive & Functional Polymers, (1998), 38, 35–49.
  87. Dang Y.M., Leong K.W.: Natural polymers for gene delivery and tissue engineering, Advanced Drug Delivery Reviews, (2006), 58, 487–499.
  88. Nair L.S., Laurecin C.T.: Biodegradable polymers as biomaterials. Progress in Polymer Science, (2007), 32, 762–798.
  89. Lloyd L.L., Kennedy J.F., Methacanon P., Peterson M., Knill C.J.: Carbohydrate polymers as wound management aids. Carbohydrate Polymers 37 (1998) 315–322.
  90. Elbert D.L.: Liquid-liquid two-phase systems for the production of porous hydrogels and hydrogel microspheres for biomedical applications: A tutorial review. Acta Biomaterialia, (2011), 7, 31–56.
  91. Eiselt P., Yeh J., Latvala R.K., Shea L.D., Mooney D.J.: Porous carriers for biomedical applications based on alginate hydrogels. Biomaterials, (2000), 21, 1921–1927.
  92. Kong H.J., Smith M.K., Mooney D.J.: Desining alginate hydrogels to maintain viability of immobilized cells. Biomaterials, (2003), 24, 4023–4029.
  93. Drury J.L., Mooney D.J.: Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials,(2003), 24, 4337–4351.
  94. Sheridan M.H., Shea L.D., Peters M.C., Mooney D.J.: Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery. Journal of Controlled Release, (2000), 64, 91–102.
  95. Kuo C.K., Ma P.X.: Ionically cross-linked alginate hydrogels as scaffolds for tissue engineering: Part 1. Structure, gelation rate and mechanical properties. Biomaterials, (2001) 22, 511–521.
  96. Koc M.L., Ozdemir U., Imren D.: Prediction of the pH and the temperature-dependent swelling behavior of Ca2+ - alginate hydrogels by artificial neural networks. Chemical Engineering Science, (2008), 63, 2913–2919.
  97. Szarek D., Laska J., Jarmundowicz W., Błażewicz S., Tabakow P., Kaliński K., Woźniak Z., Mierzwa J.: Influence of Alginates on Tube Grafts of Different Elasticity – Preliminary In Vivo Study, Journal of Biomaterials and Nanotechnology, (2012), 3, 20–30.
  98. Ashton R.S., Banerejee A., Punyani S., Schaffer D.V., Kane R.S.: Scaffolds based on degradable alginate hydrogels and poly(lactide-co-glycolide) microspheres for stem cell culture. Biomaterials, (2007), 28, 5518–5525.
  99. Banerjee A., Arha M., Choudhary S., Ashton S.R., Bhatia R.S., Schaffer D.V., Kane R.S.: The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells. Biomaterials, (2009), 30, 4695–4699.
  100. Matsuura Sh., Obara T., Tsuchiya N., Suzuki Y., Habuchi T.: Carvenous nerve regeneration by biodegradable alginate gel sponge sheet replacement without sutures. Urology, (2006), 68, 1366–1371.
  101. Suzuki Y., Kitatura M., Wu S., Kataoka K., Suzuki K., Endo K., Nishimura Y., Ide Ch.: Electrophysiological and horseradish peroxidase-tracing studies of nerve regeneration through alginate-filled gap in adult rat spinal cord. Neuroscience Letters, (2002), 138, 121–124.
  102. Prang P., Mueller R., Eljaouhari A., Heckmann K., Kunz W., Weber T., Faber C., Vroemen M., Bogdahn U., Weidner N.: The promotion of oriented axonal regrowth in the injured spinal cord by alginate-based anisotropic capillary hydrogels. Biomaterials, (2006), 27, 3560–3569.
  103. Pawar K., Muelle R., Caioni M., Prang P., Bogdahn U., Kunz W., Weidner N.: Increasing capillary diameter and the incorporation of gelatin enhance axon outgrowth in alginate-based anisotropic hydrogels. Acta Biomaterialia (2011) 7, 2826– 2834
  104. Stokolos S., Sakamoto J., Breckon Ch., Holt T., Weiss J., Tuszynski M.H.: Templated Agarose Scaffolds Support Linear Axonal Regeneration. Tissue Engineering, (2006), 12, 2777–2787.
  105. Stokolos S., Tuszynski M.H.: Freeze-dried agarose scaffolds with uniaxial channels stimulate and guide linear axonal growth following spinal cord injury. Biomaterials, (2006) 27, 443–451.
  106. Gros T., Sakamoto J.S., Blesch A., Havton L.A., Tuszynski M.H.: Regeneration of long-tract axons through sites of spinal cord injury using templated agarose scaffolds. Biomaterials, (2010), 31, 6719–6729.
  107. Zuidema M.J., Pap M.M., Jaroch B.D., Morisson F.A., Gillbert R.J.: Fabrication and characterization of tunable hydrogels blends for neural repair. Acta Biomaterialia, (2011) 7, 1634–1643.
  108. Crompton K.E., Goud J.D., Bellamkonda R.V., Gengenbach T.R., Finkelstein D.I., Horne M.K., Forsythe J.S.: Polylysinefunctionalised thermoresponsive chitosan hydrogel for neural tissue engineering. Biomaterials, (2008), 28, 441–449.
  109. ] Wang A., Ao Q., He Q., Gong X., Gong K., Gong Y., Zhao N., Zhang X.: Neural Stem Cell Affinity of Chitosan and Feasibility of Chitosan-Based Porous Conduits as Scaffolds for Nerve Tissue Engineering. Tsingua Science and Technology, (2006), 11/4, 415–420.
  110. Mo L., Yang Z., Zhang A., Li X.: The repair of the injured adult rat hippocampus with NT-3-chitosan carriers. Biomaterials, (2010), 31, 2184–2192.
  111. Yang Z., Duan H., Mo L, Qiao H., Li X.: The effect of the dosage of NT-3/chitosan carriers on the proliferation and differentiation of neural stem cells. Biomaterials, (2010) 31, 4846–4854.
  112. Everse S.J., Spraggan G., Veerapandin L., Riley M, Doolittle R.F.: Crystal structure a fragment double-D from human fibrin with two different bound ligands. Biochemistry (1998); 37(24), 8637–8642.
  113. Muszbek L., Bagdy Z., Bereczky Z., Katona E.: The involvement of blood coagulation factor XIII in fibrinolysis and thrombosis. Cardiovascular & Haematological Agents in Medical Chemistry, (2008), 6(3), 190–205.
  114. Ahmed T.A., Dare E.V., Hincke M.: Fibrin a: Versatile scaffold for tissue engineering applications. Tissue Engineering. Part B Reviews, (2008), 14, 199–215.
  115. Evans S.A., Ferguson K.H., Foley J.P., Rozanski T.A., Morey A.F.: Fibrin sealant for the management of genitourinary injuries, fistulas and surgical complications. The Journal of Urology, (2003), 169, 1360–1362.
  116. Philips J.B., King V.R., Ward Z., Porter R.A., Priestly J.V., Brown R.A.: Fluid shear in viscous fibronectin gels allows aggregation of fibrous materials for CNS tissue engineering. Biomaterials, (2004), 25 (14), 2769–79.
  117. King V.R., Hensler M., Brown R.A., Priestley J.V..: Mats made from fibronectin support oriented growth of axons in the damaged spinal cord of the adult rat. Experimental neurology, (2003), 182, 383–398.
  118. King V.R., Alovskaya A., Wei D.Y.T., Brown R.A., Priestley J.V.: The use of injectable forms of fibrin and fibronectin to support axonal ingrowth after spinal cord injury. Biomaterials, (2010), 31, 4447–4456.
  119. Ahmed Z., Idowu B.D., Brown R.A.: Stabilization of fibronectin mats with micromolar concentrations of copper. Biomaterials, (1999), 20, 201–209.
  120. King V.R., Philips J.B., Hunt-Grubbe H., Brown R., Priestley J.V.: Characterization of non-neuronal elements within fibronectin mats implanted into the damaged adult rat spinal cord. Biomaterials, (2006), 27, 485–496.
  121. King V.R., Philips J.B., Brown R.A., Prietley J.V.: The effect of treatment with antibodies to transforming growth factor beta I and beta 2 following spinal cord damage in the adult rat. Neuroscience, (2004), 126, 173–183.
  122. Soon A.S.C., Stabenfeldt S.E., Brown W.E., Barker T.H.: Engineering fibrin matrices: The engagement of polymerization pockets through fibrin knob technology for the delivery and retention of therapeutic proteins. Biomaterials, (2010), 31, 1944–1954.
  123. Taylor S.J., J. McDonald J.W. III, Sakiyama-Elbert S.E.: Controlled release of neurotrophin-3 from fibrin gels for spinal cord injury. Journal of Control Release, (2004), 98, 281–294.
  124. Price R.D., Berry M.G., Navsaria H.A.: Hyaluronic acid: the scientific and clinical evidence. Journal of Plastic, Reconstructive and Aesthetic Surgery, (2007), 60, 1110–1119.
  125. Eng D., Caplan M., Preul M., Panitch A.: Hyaluronan scaffolds: A balance between backbone functionalization a bioactivity. Acta Biomaterialia, (2010), 6, 2407–2414.
  126. Baumann M.D., Kang C.E., Tator C.H., Shoichet M.S.: Intrathecal delivery of a polymeric nanocomposites hydrogel after spinal cord injury. Biomaterials, (2010), 31, 7631–7639.
  127. Gupta D., Tator C.H., Shoichet M.S.: Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials, (2006), 27, 2370–2379.
  128. Schnell E., Klinkhammer K., Balzer S., Brook G., Klee D., Dalton P., Mey J.: Guidance of glial cell migration and axonal growth on electrospun nanofibers of poly-ε-caprolactone and a collagen/poly-ε-caprolactone blend. Biomaterials, (2007), 28, 3012–3025.
  129. Ding T., Luo Z.J., Zheng Y., Hu X-Y., Ye Z.X.: Rapid repair and regeneration of damaged rabbit sciatic nerves by tissueengineered scaffold made from nano-silver and collagen type I. Injury. Int. J. Care Injured, (2010), 41, 522–527.
  130. Wang B., Zhao Y., Lin H., Chen B., Jing Z., Zhang J., Wang X., Zhao W., Dai J.: Phenotypical analysis of adult rat olfactory ensheathing cell on 3-D collagen scaffolds. Neuroscience Letters, (2006), 401, 65–70.
  131. Jarmundowicz W. Tabakow P., Czapiga B., Międzybrodzki R., Fortuna W., Górski A.: Glejowe komórki węchowe – nadzieja w leczeniu urazów rdzenia kręgowego (Olfactory glial cells: hope in the treatment of spinal cord injuries). Neurologia i Neurochirurgia Polska (2004), 38(5), 413–420.
  132. Wang B., Han J., Gao Y., Xiao Z., Chen B., Wang X., Zhao W., Dai J.: The differentiation of rat adipose-derived stem cells into OEC-like cells on collagen scaffolds by co-culturing with OECs. Neuroscience Letters, (2007), 421, 191–196.
  133. Han Q., Jin W., Xiao Z., Ni H., Wang J., Kong J., Wu J., Liang W., Chen L., Zhao B., Dai J.: The promotion of neural regeneration in an extreme rat spinal cord injury model using a collagen scaffold containing a collagen binding neuroprotective protein and an EGFR neutralizing antibody. Biomaterials, (2010), 31, 9212–9220.
  134. Liang W., Han Q., Jin W., Xiao Z., Haung J., Ni H., Chen B., Kong J., Wu J., Dai J.: The promotion of neurological recoevery in the rat spinal cord crushed injury model by collagen-binding BDNF. Biomaterials, (2010), 31, 8634–8641.
  135. Petter-Puchner A.H., Froetscher W., Krametter-Froetscher R., Lorinson D., Redl H., van Griensven M.: The long-term neurocompatibility of human fibrin sealant and equine collagen as biomaterices in experimental spinal cord injury. Experimental and Toxicologic Pathology, (2007), 58, 237–245.
  136. Fuhrmann T., Hillen L.M., Montzka K., Woltje M., Brook G.A.: Cell-Cell interactions of human neural progenitor-derived astrocytes within a microstrutured 3D-scaffold. Biomaterials, (2010), 31, 7705–7715.
  137. ] Rezwan K., Chen Q.Z., Blaker J.J., Boccaccini.: Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials, (2006), 27, 3413–3431.
  138. Wu L., Ding J.: In vitro degradation of three-dimensional porous poly(D,L – lactide-co-glycolide) scaffolds for tissue engineering. Biomaterials, (2004), 25, 5821–5830.
  139. Kim H.D., Bae E.H., Kwon I.C.: Effect of PEG-PLA diblock copolymer on macroporous PLLA scaffolds by thermally induced phase separation. Biomaterials, 2004, 25, 2319–2329.
  140. Yang F., Qu X., Ciu W., Bei J., Yu F., Lu S., Wang S.: Manufacturing and morphology structure of polylactide-type microturbules orientation structured scaffolds. Biomaterials (2006), 27, 4923–4933.
  141. Freed L., Marquis J.C., Nohina A., Emmanual J., Kikos A.G., Langer R.: Neocartillage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers. J. Biomed Mater Res, (1993), 23, 11–23.
  142. Mikos A.G., Bao Y., Cima L.G.: Preparation of poly(glycolic-acid) bonded fiber structures for cell attachment and transplantation. J. Biomed Mater Res, (1993), 27, 183–189.
  143. Nam Y.S., Park T.G.: Biodegradable polymeric microcellular foams by modified thermally induced phase separation method. Biomaterials, (1999), 20, 1783–1790.
  144. Shi G.X., Cai Q, Wang C.X.: Fabrication of cell scaffold of poly(L-lactic acid) and poly(L-lactic-co-glycolic acid) and biocompatibility. Polymer Advanced Technology, (2002), 13, 227–232.
  145. Yang I, Wan Y.Q., Tu C.F.: Enhancing the cell affinity of macroporous poly(L-lactide) cel scaffold by a convenient surface modification method. Polym Inter, (2003), 52, 1892–1898.
  146. Kim B.S., Mooney D.J.: Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol, (1998), 16, 224–230.
  147. Vacanti C., Longer R., Schloo B., Vacanti J.P.: Synthetic polymers seeded with chondrocytes provide a template for new cartilage formation. Plast Reconstr Surg, (1991), 88, 753–759.
  148. Freed L., Grand D., Lingbin Z., Emmanual J., Marquis J.C., Langer R.: Joint resurfacing using allograft chondrocytes and synthetic biodegradable polymer scaffolds. J. Biomed. Mater. Res. (1994), 28, 891–899.
  149. Tu C.F., Cai Q, Yang I.: The fabrication and characterization of poly(lactic-acid) scaffolds for tissue engineering by improved solid-liquid phase separation.Polymer Advanced Technology, (2003), 29, 565–573.
  150. Ghasemi-Mobarakeh L., Prabhakaran M.P., Morshed M., Nasr-Esfahani M-H, Ramakrishna S.: Electrospun poly(ε- caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering. Biomaterials, (2008), 29, 4532–4539.
  151. Bechara S.L., Judson A., Popat K.C.: Template synthesized poly(ε-caprolactone) nanowire surface for neural tissue engineering. Biomaterials, (2010), 31, 3492–3510.
  152. Runge M. B, Dadsetan M., Baltrusaitis J., Knight A.M., Ruesink T., Lazcano E.A., Windebank A.J., Yaszemski M.J.: The development of electrically conductive polycaprolactone fumurate – polopyrrole composites materials for nerve regeneration. Biomaterials, (2010), 31, 5916–5926.
  153. Moore M.J., Friedman J.A., Lewellyn E.B., Mantila S.M., Krych A.J., Ameenuddin S., Knight M., Lu L., Currier B.L., Spinner R.J., Marsh R.W., Windebank A.J., Yaszemski M.J.: Multiple-channel scaffolds to promote spinal cord axon regeneration. Biomaterials, (2006), 27, 419–429.
  154. Tuinstra H.M., Aviles M.O., Shin S., Holland S.J., Zelivyanskaya M.L., Fast A.G., Ko S.Y., Margul D.J., Bartels A.K., Boehler R.M., Cummings B.J., Anderson A.J., Shea L.D.: Multifunctional, multichannel bridges that deliver neurotrophin encoding lentivrus for regeneration following spinal cord injury. Biomaterials, (2012), 33, 1618–1626.
  155. Shin S., Tuinstra H.M., Salvay D.M., Shea L.D.: Phoshatidysertine inmmobilization of lentivirus for localized gene transfer. Biomaterials, (2010), 31, 4353–4359.
  156. De Laporte L., Lei Yan A., Shea D.L.: Local gene delivery from ECM-coated poly(lactide-co-glycolide) multiple channel bridges after spinal cord injury. Biomaterials, (2009), 30, 2361–2368.
  157. Nojehdeihian H., Moztarzadeh F., Baharvand H., Nazarian H., Tahriri M.: Preparation and surface characterization of poly-L-lysine-coated PLGA microsphere scaffold containing retinoic acid for nerve tissue engineering: In vitro study. Colloids and Surface B: Biointefaces, (2009), 73, 23–29.
  158. Lee J.Y., Bashur C.A., Goldstein A.S., Schmidt C.E.: Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications. Biomaterials, (2009), 30, 4325–4335.
  159. Patist C.M., Mulder Borgerhoff M., Gautier S.E., Maquet V., Jerome 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, (2004), 25, 1569–1582.
  160. Hurtado A., Moon L.D.F., Maquet V., Blits B., Jerome R., Oudega M.: Poly (D,L – lactic acid) macroporous guidance scaffolds seeded with Schwann cells genetically modified to secrete a bi-functional neurotrophin implanted in the completely transected adult rat thoracic spinal cord. Biomaterials, (2006), 27, 430–442.
  161. Yang F., Murugan R., Ramakrishna S., Wang X., Ma Y.. H., Wang S.: Fabrication of nano-structured porous PLLA scaffold intended for nerve tissue engineering. Biomaterials, (2004), 25, 1891–1900.
  162. Wang H.B., Mullins M.E., Cregg J.M., McCarthy C.W., Gilbert R.J.: Varying the diameter of aligned electrospun fibers alters neurite outgrowth and Schwann cell migration. Acta Biomaterials, (2010), 6, 2970–2978.
  163. Hurtado A., Cregg J.M., Wang H.B., Wendell D.F., Oudega M., Gilbert R.J., McDonald J.W.: Robust CNS regeneration after complete spinal cord transection using aligned poly-L-lactic acid microfibers. Biomaterials, (2011), 32, 6068–6079.
  164. Novikov L.N., Novikova L.N., Mosahebi A., Wiberg M., Terenghi G., Kellerth J.O.: A novel biodegradable implant for neuronal rescue and regeneration after spinal cord injury. Biomaterials, (2002), 23, 3369–3376.
  165. ] Xu X.Y., Li X.T., Peng S.W., Xiao J.-F., Liu C., Fang G., Chen K.C.,Chen G.-Q.: The behaviour of neural stem cells on polyhydroxyalkanoate nanofiber scaffolds. Biomaterials, (2010), 31, 3967–3975.
  166. Wang L., Wang Z.-H., Shen C.Y., You M.L., Xiao J.F., Chen G.Q.: Differentiation of human bone marrow mesenchymal stem cells grown in terpolyesters of 3-hydroxyalkanoates scaffolds into nerve cells. Biomaterials, (2010), 31, 1691–1698.
  167. Yucel D., Kose G.T., Hasirci V.: Polyester based nerve guidance conduit design. Biomaterials, (2010), 31, 1596–1603.
  168. Mahoney J.M., Anseth K.S.: Three-dimensional growth and function of neural tissue in degradable polyethylene glycol hydrogels. Biomaterials, (2006), 27, 2265–2274.
  169. Namba R.M., Cole A.A., Bjugstad K.B., Mahoney M.J.: Development of porous PEG hydrogels that enable efficient, uniform cell-seeding and permit early neural process extension. Acta Biomaterialia, (2009) 5, 1884–1897.
  170. Wang H., Zhang S., Liao Z., Wang C., Liu Y., Feng S., Jiang X., Chang J.: PEGlated magnetic polymeric liposome anchored with TAT for delivery of drugs across the blood-spinal cord barrier. Biomaterials, (2010), 31, 6589–6596.
  171. Woerly S., Pinet E., de Robertis L., Van Diep D. Bousmina: Spinal cord repair with PHPMA hydrogel containing RGD peptides (NeuroGelTM). Biomaterials, (2011) 22, 1095–1111.
  172. Flynn L., Dalton P.D., Schoichet M.S.: Fiber templating of poly(2-hydroxyethyl methacrylate) for neural tissue engineering, Biomaterials, (2003), 24, 4265–4272.
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