Acute Phase Treatment of Spinal Cord Injury Using Hydrogel Blends Loaded with Glu

Summary

Principal Investigator: Ryan Gilbert
Abstract: The goal of this study is to develop new technology to reduce secondary injury following spinal cord injury. Currently, there are no viable treatments for patients who have sustained spinal cord injury. Experimentally, most interventions involve a bolus injection or intravenous injection of agents that reduce reactive oxygen species at the injury site. Although these treatments have improved functionality and reduced reactive oxygen species within the injury site, technology has not yet been developed to supply a continuous delivery of agents to the damaged site without the need of pumps or through the administration of several injections. Here, we present a novel biomaterial blend composed of agarose and methylcellulose. Our preliminary data shows that these blends exist as a liquid at room temperature and quickly solidify at physiological temperatures. They are injectable through a syringe for ease of application to an injured site. They also can be loaded with agents for sustained release of those agents locally without the need of an external pump. In this proposal, we introduce methodology for creating agarose/methylcellulose blends that slowly release the powerful antioxidant glutathione and the membrane stabilizing polyether polyethylene glycol. Glutathione reduces reactive oxygen species without the need of cofactors or enzymes while polyethylene glycol repairs cellular membranes susceptible to lipid peroxidation. Thus, both agents loaded into a hydrogel material have the potential of being slowly released during the period of time when reactive oxygen species concentrations are the highest. This proposal main aims are to determine the release profiles of glutathione and polyethylene glycol from the agarose/methylcellulose blend. Once the release profiles have been determined, blends with loaded glutathione and polyethylene glycol will be placed into a rat compressive spinal cord injury model. Using immunohistochemical and locomotor analytical techniques, the blends that release glutathione and polyethylene glycol will be compared to other controls to determine if the blends are superior to other more traditional modes of administering a therapeutic. Such information would clearly determine whether an injectable, degradable, fast-gelling hydrogel can effectively delivery agents to more efficiently reduce secondary injury following spinal cord injury. Current techniques to administer agents to reduce secondary injury following spinal cord trauma involve bolus injection into the injury site or intravenous injection. Using biomaterials, hydrogels made from agarose and methylcellulose can be loaded with agents that reduce secondary injury so that these agents can be released for a sustained period of time. The research described in this proposal will determine if hydrogels loaded with glutathione and polyethylene glycol are more effective at reducing secondary injury than bolus injections of these agents in a rat spinal cord injury model.
Funding Period: 2009-01-01 - 2011-12-31
more information: NIH RePORT

Top Publications

  1. pmc A rapid, quantitative method for assessing axonal extension on biomaterial platforms
    Jared M Cregg
    Regeneration and Repair Laboratory, Department of Biomedical Engineering, Michigan Technological University, Houghton, Michigan 49931 1295, USA
    Tissue Eng Part C Methods 16:167-72. 2010
  2. ncbi Fabrication and characterization of tunable polysaccharide hydrogel blends for neural repair
    Jonathan M Zuidema
    Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931 1295, USA
    Acta Biomater 7:1634-43. 2011
  3. ncbi Biomaterial design considerations for repairing the injured spinal cord
    Ryan J Gilbert
    Regeneration and Repair Laboratory, Department of Biomedical Engineering, Michigan Technological University, Houghton, MI, USA
    Crit Rev Biomed Eng 39:125-80. 2011
  4. pmc Robust CNS regeneration after complete spinal cord transection using aligned poly-L-lactic acid microfibers
    Andres Hurtado
    International Center for Spinal Cord Injury, Hugo W Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA
    Biomaterials 32:6068-79. 2011
  5. ncbi Controlled release of 6-aminonicotinamide from aligned, electrospun fibers alters astrocyte metabolism and dorsal root ganglia neurite outgrowth
    Nicholas J Schaub
    Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931 1295, USA
    J Neural Eng 8:046026. 2011

Scientific Experts

  • Ryan J Gilbert
  • Andres Hurtado
  • Jonathan M Zuidema
  • Nicholas J Schaub
  • David B Jaroch
  • Jared M Cregg
  • Faith A Morrison
  • Matthew M Pap
  • Martyn R Smith
  • Daniel C Clupper
  • Sherri L Wiseman
  • Nicole M Pietrzak-Goetze

Detail Information

Publications5

  1. pmc A rapid, quantitative method for assessing axonal extension on biomaterial platforms
    Jared M Cregg
    Regeneration and Repair Laboratory, Department of Biomedical Engineering, Michigan Technological University, Houghton, Michigan 49931 1295, USA
    Tissue Eng Part C Methods 16:167-72. 2010
    ..We suggest that this simple protocol for quantifying material biocompatibility offers an analysis strategy that can be used universally to the same end...
  2. ncbi Fabrication and characterization of tunable polysaccharide hydrogel blends for neural repair
    Jonathan M Zuidema
    Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931 1295, USA
    Acta Biomater 7:1634-43. 2011
    ..Our results show that softer, more positively charged polysaccharide hydrogel blends allow for greater neuron attachment and neurite extension, showing their promise as CNS regeneration scaffolds...
  3. ncbi Biomaterial design considerations for repairing the injured spinal cord
    Ryan J Gilbert
    Regeneration and Repair Laboratory, Department of Biomedical Engineering, Michigan Technological University, Houghton, MI, USA
    Crit Rev Biomed Eng 39:125-80. 2011
    ....
  4. pmc Robust CNS regeneration after complete spinal cord transection using aligned poly-L-lactic acid microfibers
    Andres Hurtado
    International Center for Spinal Cord Injury, Hugo W Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA
    Biomaterials 32:6068-79. 2011
    ..Our findings outline a form of regeneration within the central nervous system that holds important implications for regeneration biology...
  5. ncbi Controlled release of 6-aminonicotinamide from aligned, electrospun fibers alters astrocyte metabolism and dorsal root ganglia neurite outgrowth
    Nicholas J Schaub
    Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931 1295, USA
    J Neural Eng 8:046026. 2011
    ..However, neurite outgrowth was stunted by fibers that contained 20% 6AN. These results show that 6AN release from aligned, electrospun fibers can decrease astrocyte activity while still directing axonal outgrowth...