Heterogeneous PHPMA hydrogels for tissue repair and axonal regeneration in the injured spinal cord.

A biocompatible heterogeneous hydrogel of poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) showing an open porous structure, viscoelastic properties similar to the neural tissue and a large surface area available for cell interaction, was evaluated for its ability to promote tissue repair and axonal regeneration in the transected rat spinal cord. After implantation, the polymer hydrogel could correctly bridge the tissue defect, from a permissive interface with the host tissue to favour cell ingrowth, angiogenesis and axonal growth occurred within the microstructure of the network. Within 3 months the polymer implant was invaded by host derived tissue, glial cells, blood vessels and axons penetrated the hydrogel implant. Such polymer hydrogel matrices which show neuroinductive and neuroconductive properties have the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost of tissue.

[1]  M. Bates,et al.  Regrowth of axons in lesioned adult rat spinal cord: promotion by implants of cultured Schwann cells , 1994, Journal of neurocytology.

[2]  W. Young,et al.  Endogenous Repair after Spinal Cord Contusion Injuries in the Rat , 1997, Experimental Neurology.

[3]  Balentine Jd.  Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. , 1978 .

[4]  E. W. Washburn.  Note on a Method of Determining the Distribution of Pore Sizes in a Porous Material. , 1921, Proceedings of the National Academy of Sciences of the United States of America.

[5]  C. Tsakiroglou,et al.  A new simulator of mercury porosimetry for the characterization of porous materials , 1990 .

[6]  J. Horvat,et al.  Co-transplantation of embryonic neural tissue and autologous peripheral nerve segments to severe spinal cord injury of the adult rat. Guided axogenesis from transplanted neurons. , 1991, Restorative neurology and neuroscience.

[7]  Alan R. Harvey,et al.  Hydrogels Containing Peptide or Aminosugar Sequences Implanted into the Rat Brain: Influence on Cellular Migration and Axonal Growth , 1997, Experimental Neurology.

[8]  O. Cebeci.  The intrusion of conical and spherical pores in mercury intrusion porosimetry , 1980 .

[9]  H. Müller,et al.  Astroglial neurotrophic and neurite-promoting factors. , 1995, Pharmacology & therapeutics.

[10]  B. Bregman.  Spinal cord transplants permit the growth of serotonergic axons across the site of neonatal spinal cord transection. , 1987, Brain research.

[11]  M. L. Shively.  Analysis of mercury porosimetry for the evaluation of pore shape and intrusion-extrusion hysteresis. , 1991, Journal of pharmaceutical sciences.

[12]  H. Burton,et al.  Implantation of cultured sensory neurons and schwann cells into lesioned neonatal rat spinal cord. II. Implant characteristics and examination of corticospinal tract growth , 1990, The Journal of comparative neurology.

[13]  Eva Syková,et al.  The Extracellular Space in the CNS: Its Regulation, Volume and Geometry in Normal and Pathological Neuronal Function , 1997 .

[14]  H. Goldsmith,et al.  Axonal regeneration after spinal cord transection and reconstruction , 1992, Brain Research.

[15]  A. Harvey,et al.  The migration and intermixing of donor and host glia on nitrocellulose polymers implanted into cortical lesion cavities in adult mice and rats , 1993, International Journal of Developmental Neuroscience.

[16]  G W Plant,et al.  Neural tissue engineering: from polymer to biohybrid organs. , 1996, Biomaterials.

[17]  A. Björklund,et al.  Immortalized neural progenitor cells for CNS gene transfer and repair , 1997, Trends in Neurosciences.

[18]  M. Bousmina,et al.  Rheology/morphology/flow conditions relationships for polymethylmethacrylate/rubber blend , 1996 .

[19]  A. Harvey,et al.  Axonal growth within poly (2-hydroxyethyl methacrylate) sponges infiltrated with Schwann cells and implanted into the lesioned rat optic tract , 1995, Brain Research.

[20]  I. Vorisek,et al.  Ischemia-Induced Changes in the Extracellular Space Diffusion Parameters, K+, and pH in the Developing Rat Cortex and Corpus Callosum , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  A. Harvey,et al.  Regrowth of axons within Schwann cell-filled polycarbonate tubes implanted into the damaged optic tract and cerebral cortex of rats. , 1994, Restorative neurology and neuroscience.

[22]  K. Dušek.  Phase separation during the formation of three‐dimensional polymers , 1965 .

[23]  E. Transfeldt,et al.  The effect of the platelet derived wound healing formula and the nerve growth factor on the experimentally injured spinal cord , 1996, Spinal Cord.

[24]  E. Joosten,et al.  Collagen implants and cortico‐spinal axonal growth after mid‐thoracic spinal cord lesion in the adult rat , 1995, Journal of neuroscience research.

[25]  F T Gentile,et al.  Poly(ethylene oxide)‐grafted thermoplastic membranes for use as cellular hybrid bio‐artificial organs in the central nervous system , 1994, Biotechnology and bioengineering.

[26]  N. Kleitman,et al.  Axonal regeneration into Schwann cell‐seeded guidance channels grafted into transected adult rat spinal cord , 1995, The Journal of comparative neurology.

[27]  L. Guth,et al.  Experimental Analysis of Progressive Necrosis after Spinal Cord Trauma in the Rat: Etiological Role of the Inflammatory Response , 1997, Experimental Neurology.

[28]  A. Mikos,et al.  Review: Hydrogels for cell immobilization , 2000, Biotechnology and bioengineering.

[29]  C. Nicholson,et al.  Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum. , 1981, The Journal of physiology.

[30]  C. T. Montgomery,et al.  Axonal Growth into Tubes Implanted within Lesions in the Spinal Cords of Adult Rats , 1996, Experimental Neurology.

[31]  R. McKay,et al.  Neuronal progenitors as tools for cell replacement in the nervous system , 1996, Current Opinion in Neurobiology.

[32]  Alan R. Harvey,et al.  Cultured rat neuronal and glial cells entrapped within hydrogel polymer matrices: a potential tool for neural tissue replacement , 1996, Neuroscience Letters.

[33]  J. Kopeček,et al.  Poly[N‐(2‐hydroxypropyl)methacrylamide]. IV. Heterogeneous polymerization , 1978 .

[34]  Christine E. Krewson,et al.  Cell aggregation and neurite growth in gels of extracellular matrix molecules , 1994, Biotechnology and bioengineering.

[35]  L. Wolman.  Axon regeneration after spinal cord injury , 1966, Paraplegia.

[36]  Alan R. Johnson,et al.  REGENERATION IN THE VERTEBRATE CENTRAL NERVOUS SYSTEM: PHYLOGENY, ONTOGENY, AND MECHANISMS , 1995, Biological reviews of the Cambridge Philosophical Society.

[37]  J. E. Mayer,et al.  Tissue engineering scaffolds using superstructures. , 1996, Biomaterials.

[38]  F. Dullien,et al.  Characterization of pore structure by a combination of quantitative photomicrography and mercury porosimetry , 1974 .

[39]  G. Moonen,et al.  Preparation of a macroporous biodegradable polylactide implant for neuronal transplantation. , 1995, Journal of biomedical materials research.

[40]  H. Spiess,et al.  R. B. Bird, C. F. Curtiss, R. C. Armstrong. O. Hassager: Dynamics of polymeric liquids — Vol. 2: Kinetic Theory, 2. Ausgabe. 437 Seiten, Preis: £ 59.65. John Wiley + Sons, New York, Brisbane, Toronto, Singapore 1987 , 1987 .

[41]  J L Nation,et al.  A new method using hexamethyldisilazane for preparation of soft insect tissues for scanning electron microscopy. , 1983, Stain technology.

[42]  Myron Spector,et al.  The Effects of Collagen-Based Implants on Early Healing of the Adult Rat Spinal Cord , 1997 .

[43]  N. Tamaki,et al.  Biomechanics of hydrocephalus: a new theoretical model. , 1987, Neurosurgery.

[44]  A. Lehmenkühler,et al.  Extracellular space parameters in the rat neocortex and subcortical white matter during postnatal development determined by diffusion analysis , 1993, Neuroscience.

[45]  Antonios G. Mikos,et al.  Biodegradable polymer scaffolds to regenerate organs , 1995 .

[46]  S. Dunnett,et al.  Long-Term Survival of Human Central Nervous System Progenitor Cells Transplanted into a Rat Model of Parkinson's Disease , 1997, Experimental Neurology.

[47]  J. Seidl,et al.  Makroporöse Styrol-Divinylbenzol-Copolymere und ihre Verwendung in der Chromatographie und zur Darstellung von Ionenaustauschern , 1967 .

[48]  E. Jones,et al.  Growth of corticospinal axons on prosthetic substrates introduced into the spinal cord of neonatal rats. , 1987, Brain research.

[49]  J. Andrade.  Hydrogels for medical and related applications , 1976 .

[50]  E. Sykova,et al.  Heterogeneous and anisotropic diffusion in the developing rat spinal cord , 1997, Neuroreport.

[51]  J. Silver,et al.  An in vitro model of wound healing in the CNS: Analysis of cell reaction and interaction at different ages , 1989, Experimental Neurology.

[52]  K. Ulbrich,et al.  Synthetic Polymer Matrices for Neural Cell Transplantation , 1993, Cell transplantation.

[53]  O. Lindvall,et al.  Transplantation into the human brain: present status and future possibilities. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[54]  S. Carbonetto,et al.  Nerve fiber growth on defined hydrogel substrates. , 1982, Science.

[55]  J. J. Bernstein,et al.  Transplantation of cultured fetal spinal cord grafts, grown on a histocompatible substrate, into adult spinal cord , 1986, Brain Research.

[56]  A. Chvátal,et al.  Extracellular Volume Fraction and Diffusion Characteristics during Progressive Ischemia and Terminal Anoxia in the Spinal Cord of the Rat , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[57]  S. Woerly.  Hydrogels for neural tissue reconstruction and transplantation. , 1993, Biomaterials.

[58]  K. Ulbrich,et al.  Intracerebral Implantation of Hydrogel-Coupled Adhesion Peptides: Tissue Reaction , 1995, Journal of neural transplantation & plasticity.

[59]  S. Woerly,et al.  Transected spinal cords grafted with in situ self-assembled collagen matrices , 1990, Neuroscience.

[60]  A. Blight,et al.  Cellular morphology of chronic spinal cord injury in the cat: Analysis of myelinated axons by line-sampling , 1983, Neuroscience.

[61]  S. Woerly,et al.  Intracerebral implantation of synthetic polymer/biopolymer matrix: a new perspective for brain repair. , 1990, Biomaterials.

[62]  M. Berry,et al.  Growth factors in CNS repair and regeneration. , 1994, Progress in growth factor research.