Date of Award

Fall 2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering - (Ph.D.)

Department

Biomedical Engineering

First Advisor

Bryan J. Pfister

Second Advisor

Steven W. Levison

Third Advisor

Cheul H. Cho

Fourth Advisor

George Collins

Fifth Advisor

Raquel Perez-Castillejos

Sixth Advisor

Chirag D. Gandhi

Abstract

Nerve regeneration following a peripheral nerve injury often relies on growth cone- mediated guidance and the presence of Schwann cells to support the regenerating axons and remyelinate portions of denervated nerve pathways. The emphasis of this work is to develop a synthetic nervous tissue construct that contains similar basal lamina or extracellular matrix to peripheral nerve in order to achieve a level of effectiveness in nerve repair and future peripheral nerve regeneration applications. To this end, three- dimensional nervous tissue constructs consisting of type I collagen are fabricated into a composite biomaterial scaffold to promote contact-guided growth of neuronal and glial cultures in vitro. The growth of adult tissue on these collagen-based materials is further evaluated. These constructs are assembled by wet spinning synthetic collagen fibers and loading them onto a soft collagen gel matrix composed of type I collagen.

Wet-spun collagen fibers serve as a rigid substrate to reinforce the gel while facilitating axon growth cone advancement along a polarized direction. In this study, the emphasis is to characterize the mechanical stability, thermal properties, and swelling response of the collagen fiber component of the construct. To improve these properties in the fiber component, chemical cross-linking with genipin and glutaraldehyde are evaluated. The result is a construct exhibiting mechanical integrity for facilitating adult Schwann cell orientation and the guidance and survival of adult dorsal root ganglion neurons in a co-culture 3-D system.

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