Author's School

School of Engineering & Applied Science

Author's Department/Program

Biomedical Engineering

Language

English (en)

Date of Award

5-24-2009

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Shelly Sakiyama-Elbert

Abstract

This thesis work sought to develop a biomaterial to further the understanding of affinity-based 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, the ABDS effectively sequestered and slowed the release of glial-derived growth factor: GDNF) and promoted neurite extension in vitro. The efficacy of the ABDS and GDNF in vivo to promote nerve regeneration in a rat sciatic nerve critical defect was determined through histomorphometric outcomes. Histomorphometric measures revealed that the ABDS and GDNF promoted nerve regeneration similar to the isograft 6 weeks after treatment in measures of fiber density, nerve regeneration quality, fiber maturity, and the fiber organization of the regenerating nerve. Functional recovery and modality specific nerve regeneration were studied with the ABDS and growth factor in a rat sciatic nerve critical defect 12 weeks after treatment. Behavioral outcomes and electrophysiological responses including evoked motor responses were similar to functional outcomes in the isograft with the delivery of NGF, but superior to the isograft with the delivery of GDNF. Both GDNF and NGF delivery supported the regeneration of motor and sensory neurons equivalent to the isograft, as assessed by retrograde labeling. Overall, this work indicates that affinity-based growth factor delivery from fibrin matrices enhances nerve regeneration.

Comments

Permanent URL: http://dx.doi.org/10.7936/K7C24TFM

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