Growth Factor Delivery From Fibrin Matrics Containing Affinity-Based Delivery Systems To Treat Peripheral Nerve Injury

Abstract

OF DISSERTATION GROWTH FACTOR DELIVERY FROM FIBRIN MATRICS CONTAINING AFFINITY-BASED DELIVERY SYSTEMS TO TREAT PERIPHERAL NERVE INJURY By Matthew David Wood Doctor of Philosophy in Biomedical Engineering Washington University in St. Louis, 2009 Chairperson: Shelly E. Sakiyama-Elbert, Ph.D. This thesis work sought to develop a biomaterial to further the understanding of affinitybased delivery and to serve as a potential treatment for peripheral nerve injury. The use of an affinity-based delivery system (ABDS) with growth factors in a nerve guidance conduit (NGC) was hypothesized to promote nerve regeneration and functional recovery following a critical nerve defect. Evaluation of affinity-based delivery using peptides with varying binding affinity for heparin determined that peptide binding affinity for heparin affected the release rate and biological activity of nerve growth factor (NGF) in vitro. The ABDS presented biologically active NGF, which promoted neurite extension regardless of peptide binding affinity for heparin. The efficacy of the ABDS in vivo to promote nerve regeneration in a rat sciatic nerve critical defect was determined through histomorphometric outcomes. The ABDS with any affinity peptide and NGF was similar to the isograft in aspects of nerve regeneration including: fiber density, nerve regeneration quality, fiber maturity, and the fiber organization of the regenerating nerve 6 weeks after treatment. Alternatively,