An Injectable Multifunctional Gel to Treat Spinal Cord Injury

Va Boston Health Care System, Boston MA

Investigators

Abstract

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.