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.
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.
