Date of Award

2014

Embargo Period

1-1-2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cell Biology and Regenerative Medicine

College

College of Graduate Studies

First Advisor

Robin C. Muise-Helmericks

Second Advisor

Amy Bradshaw

Third Advisor

Michael Kern

Fourth Advisor

Rick Visconti

Fifth Advisor

John Vournakis

Abstract

Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine diatom, results in increases in wound closure, antibacterial activities and innate immune responses. Treatment with nanofibers results in increased defensin, small antimicrobial peptides, expression both in vitro and in vivo. Induction of defensing expression results in bacterial clearance in a cutaneous wound model. We have also shown that Akt1 plays a central role in the regulation of these activities. We show that pGlcNAc treatment of cutaneous wounds in mice results in decreased scar sizes. Additionally, treatment of cutaneous wounds with pGlcNAc results in increased elasticity and a rescue of tensile strength. Masson Trichrome staining suggests that pGlcNAc treated wounds exhibit decreased collagen content as well as increased collagen alignment with collagen fibers oriented similarly to unwounded tissue. Utilizing a fibrin gel assay to analyze the effect of pGlcNAc nanofiber treatment on fibroblast alignment in vitro, pGlcNAc stimulation of embedded fibroblasts results in fibroblasts alignment as compared to untreated controls, by a process that is Akt1 dependent. Our data shows that in Akt1 null animals pGlcNAc treatment does not increase tensile strength or elasticity. Taken together, our findings suggest that pGlcNAc nanofibers stimulate an Akt1 dependent pathway that results in wound closure, the proper alignment of fibroblasts, decreased scarring, and increased tensile strength during cutaneous wound healing.

Rights

All rights reserved. Copyright is held by the author.

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