The overall goal of the proposed Pilot project is to perform an animal investigation to evaluate an injectable multifunctional collagen gel to treat spinal cord injuries (SCIs). A novel and criticl feature of the gel is its ability to be independently tuned as both a scaffold to accommodate the migration of endogenous cells into the cavitary defect formed after SCI and as a vehicle for the controlled release of therapeutic agents. The rate of gelation, stiffness, and resistance to degradation of the type I collagen gel will be controlled by the addition of genipin, an amine reactive covalent cross-linker with low cytotoxicity and potential therapeutic benefit. Our supposition is that attraction of astrocyte migration into the gel will have 2 beneficial effects: reduce the glial scar; and facilitate attendant neurite ingrowth into the gel. In order to enhance the infiltration of the gel-filled defect with astrocytes, a known chemoattractant for these cells, fibroblast growth factor (FGF)-2, will be incorporated into the collagen solution prior to its injection. The FGF-2 will be contained in lipid microtubules (LMTs) to control its release. The gel formulations will be evaluated in a hemi-resection defect model in the rat spinal cord. The 2 specific objectives of this pilot project are directed toward the evaluation of new technology for treating cavitary defects in SCI: 1) evaluate, in vitro, FGF-2-containing LMTs (viz., loading efficiency, release kinetics, and retained bioactivity) and the mechanical behavior (viz., gel time and modulus of elasticity) of collagen-genipin gels incorporating the LMTs in order to determine the most promising formulation to evaluate in vivo; and 2) evaluate by histomorphometry and hindlimb locomotor behavior the response to injection of a select formulation of the LMT- containing collagen-genipin gel in a standardized hemi-resection defect in the rat spinal cord.
That there are currently no satisfactory procedures for treating cavitary defects resulting from spinal cord injury (SCI), prompted this investigation of an injectable gel to serve as a scaffold t accommodate endogenous cell migration into the defect. The gel, which will incorporate nanoparticles containing a chemoattractant for astrocytes and endothelial cells, will be tested in a rat model.
