Our objective is to develop a new biomaterial, a salmon-derived fibrin gel, which will bridge injured CNS tissue, support and promote axonal sprouting and growth, and deliver neurotrophic factors and cells.
In Aim #1 we will test the efficacy of salmon-derived fibrin gels in animal models of CNS injury. Using the rat dorsal hemi-section, contusion, and fluid percussion models, we will compare the salmon material to human-derived fibrin gels for efficacy, inflammatory response, and possible functional changes.
In Aim #2 we will seek to identify the growth-promoting factors that are involved in the salmon gels. We will determine if there is a small active molecule bound to the fibrinogen, and what properties of the fibrinogen molecule are important.
In Aim #3 we plan pre-clinical studies of viral clearance, immunogenicity, and stability that are necessary for FDA approval of salmon fibrinogen and thrombin. We will spike the proteins with virus, and determine combinations of heat and gamma radiation that will achieve viral reduction, preserve protein efficacy, and not result in immunogenicity. Tissues from treated rats (Aim #1) will be examined for inflammatory response, and plasma samples taken for antibody studies. The cost of spinal cord and brain injury in both dollars and human suffering is a major public health issue. If the neurosurgeon could intervene with a material that promotes neuronal regrowth and connectivity, the impacts for the patient and for society are enormous. ? ?
| Sharp, Kelli G; Dickson, Amanda R; Marchenko, Steve A et al. (2012) Salmon fibrin treatment of spinal cord injury promotes functional recovery and density of serotonergic innervation. Exp Neurol 235:345-56 |
| Weisshaar, Christine L; Winer, Jessamine P; Guarino, Benjamin B et al. (2011) The potential for salmon fibrin and thrombin to mitigate pain subsequent to cervical nerve root injury. Biomaterials 32:9738-46 |
| Laidmae, Ivo; Salum, Tiit; Sawyer, Evelyn S et al. (2010) Characterization of the biological effect of fish fibrin glue in experiments on rats: immunological and coagulation studies. J Biomed Mater Res A 93:29-36 |
| Uibo, Raivo; Laidmäe, Ivo; Sawyer, Evelyn S et al. (2009) Soft materials to treat central nervous system injuries: evaluation of the suitability of non-mammalian fibrin gels. Biochim Biophys Acta 1793:924-30 |
